Atopy – STG Makise Lifeup USA

Supplements, Medicine and Ointment for Psoriasis: Effective and Unique Treatment From Japan

CustomerTeam — Thu, 09 Apr 2020 08:05:35 +0000

With proper guidelines, supplements, ointments, and treatment, you can be free from psoriasis within four months.

I am not a dermatologist but a general physician. I see psoriasis as an inside-out disease which is a different view from the ordinary dermatologists. For years, I’ve been using our special ointments, oral medication, and supplements for the treatment of psoriasis.

Psoriasis is a non-contagious inflammatory skin disease associated with rapid skin cell multiplication. A variety of factors like hereditary, infection, environment, medications, stress, smoking, and genetics cause Psoriasis. The most common symptom of psoriasis is dry and itchy skin, formation of red patchy inflamed skin and stiff swollen joints.

It might sound strange to a dermatologist, but the actual cause of psoriasis is viruses. These two to three kinds of viruses attack the patient’s abnormal genes variants linked with the onset of psoriasis. Consequently, the immune system functions differently and causes inflammation. For this reason, immunosuppressant drugs such as methotrexate or cyclosporine help ease psoriasis significantly.

As the virus triggers psoriasis and alters the immune system, there must be a selection of holistic approaches for the effective treatment of psoriasis.

1. Use of ointments for psoriasis treatment

With more than 15 years of research, analysis, and completion, and treatment of more than 40,000 patients with varieties of skin diseases, we have created a unique formula for psoriasis treatment. With proven assurance, we have developed three special ointments – PS (1), MAS (1), and MA (1) to speed up the cure of psoriasis.

Not only this, but it also helps to cure varied forms of eczemas due to psoriasis, Pustulosis palmaris et plantaris (PPP), atopic dermatitis, nodular prurigo, and many other skin conditions. But, in cases like fungus or serious malignancy such as mycosis fungoides (cutaneous T-cell lymphoma), these ointments cannot cure eczema.

The psoriasis ointment list with its ingredients are as follows:

PS(1): difluprednate, clofibrate, jojoba oil, vegetable squalene, lanolin hydrous, macadamia nut oil, fermented extract of leaves of shell ginger, very fine powder of 5 kinds of mineral ores.

MAS(1): difluprednate and clobetasol propionate, licorice oil, moringa oil, macadamia nut oil, fermented extract of leaves of shell ginger, vitamin B1, B2, B12, alpha-lipoic acid, very fine powder of 5 kinds of mineral ores.

MA(1): triamcinolone acetonide and clobetasol propionate, moringa oil, macadamia nut oil, vitamin B1, B2, B12, alpha-lipoic acid, fermented extract of leaves of shell ginger, very fine powder of 5 kinds of mineral ores.

From the safety perspective, though these psoriasis ointments contain corticosteroid: a steroid hormone, the side effects are merely present. Unlike others, our ointments emit infrared rays from the fine powder of 5 stones. It leads to quick restoration of the skin.
PS (1) and MAS (1) are effective for the treatment of Psoriasis Vulgaris. Despite this, its efficacy seems to depend upon factors like race, climate, and food. For cases with fair and thin skin, MAS (1) is more potent. Hence, at first, I prescribe both PS (1) and MAS (1) to the patients and allow them to observe their efficacy for a week.

Here’s a case example: I recommend applying PS (1) on the lesion on the left side of the body and MAS (1) on the right side twice a day for a week to the patient. Later, the patient can identify the efficiency of ointment of psoriasis for his condition.
Also, for the treatment of Guttate psoriasis, MA (1) is recommended.

2. Two Important Oral Medication for Psoriasis

The first treatment step includes eradicating viruses that modulate the immune system using medications having insignificant side effects. The following two medicines have minimal side effects compared to immunosuppressant pills:

a. Erythromycin (Erythrocin® 200 mg)

Erythromycin is an antibiotic used in the treatment and prevention of several bacterial infections. Theoretically, antibiotics are only effective against bacteria, but realistically, Erythromycin seems to be effective against the virus as well. Therefore, I recommend this as good medicine for psoriasis.

As for myself, whenever I travel overseasthemin by long flights, I always take Erythromycin as prophylactic for two days before the flight. It works for the prevention of both bacterial and viral infections.

How to take: 4 tablets/day — Morning (2 tablets) and Evening (2 tablets). But the process of taking is unique. Please take the medication as follows:

As shown above, take the 4 tablets for four days and don’t take them for the following three days. For example, if you begin from Sunday, take 4 tablets/ day for Monday, Tuesday, Wednesday. And on Thursday, Friday, Saturday, you should discontinue the medication. You should again continue the same pattern by taking 4 tablets every day from the next Sunday to Wednesday and keeping a gap from Thursday to Saturday.

Repeat this cycle for 12 weeks (almost 3 months).

*If you are allergic to Macrolides, please don’t take this antibiotic.

b. Cepharanthine (Cepharanthin® 1 mg)

It is a naturally occurring alkaloid extracted from the plant Stephania cepharantha Hayata. In Japan, Cepharanthin® is a somewhat obscure medicine. As it is inexpensive, doctors are not interested in prescribing it (Doctors prefer costly drugs for business!!), and Cepharanthine is often underrated. Despite its value, it helps to cure diseases like Multiple Sclerosis, Ulcerative Colitis, and Hypothyroidism. Being able to modulate the immune system, Cepharanthin is beneficial in the cure of psoriasis.

Now, only one Japanese company manufactures Cepharanthin. I do hope the other companies continue the production of this notably potent psoriasis pill.

How to take: 3 to 4 tablets/day. Generally, you must continue it for 3 months.

It has few side effects in contrast to biologics such as Stelara or immunosuppressants such as MTX.

Q. How to take these two medicines for the treatment of psoriasis?

A. For the first month, use Cepharanthine only. In the following second and third months, take both Cepharanthine and Erythromycin. Finally, in the fourth month followed, take Erythromycin only. From the third month, you can also begin to take natural supplements. I especially prescribe this to undergo the best psoriasis treatment.

3. Supplements for Psoriasis

a. Natural supplement for psoriasis

Shell Ginger Supplement (JIPANG Ginger®) 1400 mg ~ 2000 mg/day

b. Vitamin and other supplements for psoriasis

1) Lipids
Psoriasis patients manifest significant lipid abnormalities. Though this might not apply to all cases, I have seen psoriasis patients with high blood cholesterol recover miraculously by cholesterol-lowering statin drugs. Dermatologists, however, disregard this fact as its efficacy is controversial.

If you search “statin psoriasis” you can find fascinating articles such as:(https://www.webmd.com/skin-problems-and-treatments/psoriasis/news/20100308/cholesterol-drugs-may-treat-psoriasis#1). There are opposing articles likewise, but I think it is worth trying. Although I am against statin drugs for lowering cholesterol, I still recommend them for psoriasis. Particularly Simvastatin, marketed under the trade name Zocor, shows effectiveness on psoriasis.

2) Biotin
Biotin (a kind of vitamin B-complex) falls among the essential vitamins that help cure psoriasis. This vitamin is required for fat metabolism and thus influences skin health.
Patients using antibiotics, intaking only α-lipoic acid, following dialysis, and consuming an excessive amount of egg white are likely to be deficient in this vitamin. Besides, people taking sleeping pills, antidepressants, and antiepileptic drugs for a longer duration also lack biotin. As some species of lactic acid bacteria feed on biotin, you must limit intake of yogurt cautiously.

Dosage of biotin for psoriasis: 10 mg to 15 mg/day. Please do not mistake the unit. It is 10 mg to 15 mg (10,000 mcg to 15,000 mcg), not 10 mcg to 15 mcg (10 μg to 15 μg). Many biotin supplements contain 5000 mcg of biotin per capsule, in such cases, 2-3 capsules per day are recommended.

You should continue biotin supplements for at least six months. You must discontinue smoking, as biotin does not work efficiently with smoking.

3) Omega 3 Unsaturated Fatty Acid: 3000 mg to 4000 mg /day

Omega-3-fatty acids are one of the best supplements for psoriasis as it plays a vital role in reducing inflammation. Harp Seal Oil is very stable, contains EPA, DHA, and DPA, and is the best source of omega-3 fatty acids. These essential fatty acids circulate in human blood and maintain soft, plaque-free arterial walls. They also reduce inflammation and produce a healing effect on the cells of the skin. Furthermore, from these unsaturated fatty acids, beneficial eicosanoids are metabolized, which facilitates the cure of psoriasis.

But, if you love such a cute animal as Harp Seal and would not like to sacrifice their lives, you can choose Sacha Inchi Oil. And if you would like to economize, Flaxseed Oil can be a good substitute for omega-3 fatty acids.

4) Inositol (750 mg to 1000 mg /day)
Inositol is a vitamin-like substance synthesized in small quantities in our bodies. Phytate, naturally present in cereals and grains, acts as a precursor of inositol. Phytin, phytic acid, and inositol have different functions, such as maintaining cholesterol levels and promoting skin health. In some cases, psoriasis patients suffer from hyperlipidemia. Hence, rectifying it reduces the severity of psoriasis and is a potent supplement for psoriasis.

5) Zinc (40 mg/day Zinc Monomethionate or Zinc Picolinate)
Zinc regenerates collagen and maintains skin composition, being a vital mineral supplement for psoriasis. It is readily available online or at any vitamin shop and is reasonably priced. However, like copper, if you take zinc supplements at a higher dose for a long time, side effects are anticipated. Therefore, a doctor’s consultation is necessary. Zinc supplement is not advisable for hepatitis patients or those who are the carrier of the hepatitis virus.

6) Copper (4 mg to 6 mg/day)
Viral infections lead to the onset of psoriasis. Although mainstream medicines disagree with this viewpoint, copper suppresses the growth of the virus, making it another effective psoriasis supplement. Besides, they are affordable and available easily.

You should not take copper supplements continuously for a longer duration. You can take it for no longer than 3 months. After a gap of a month, you can again take it for 3 months. You can continue the cycle in a similar pattern.

7) Selenium: 200 mcg/day
Another effective mineral supplement for psoriasis is selenium. It synthesizes the glutathione peroxidase enzyme. This enzyme protects the cell from oxidative damage by neutralizing free radicals.

Selenium forms selenocysteine, an enzyme required in the activation of the thyroid hormone. It helps to convert tetraiodothyronine (T4) to triiodothyronine (T3). The deficiency of active thyroid hormone T3 adversely affects psoriasis.

8) Magnesium (200 mg/day Magnesium Glycinate is recommended)
About 325 kinds of enzymes are directly dependent on magnesium for functioning. If our body lacks adequate magnesium, the physiological function and metabolism will paralyze. It has a detoxification effect on toxic substances, which helps expel heavy metals and their complexes outside the body quickly.

The nicotine of cigarettes or a large amount of alcohol (the moderate amount is not a problem) can drain magnesium. Also, the intake of magnesium can impair the action of hypothyroidism drugs like levothyroxine. A common side effect of intake of magnesium supplements is passing of soft stool and onset of diarrhea. Hence, take the supplement under supervision.

9) Vitamin K2 as Menatetrenone
Tumor necrosis factor α (TNFα) antagonists play an indispensable role in curing psoriasis. Due to this reason, biologics such as infliximab (Remicade®), etanercept (Enbrel®), and adalimumab (Humira®) are in use for treatment.

Yet, the approval of these biologics is contradictory in patients with diseases like chronic leg ulcers, chest infections, congestive cardiac failure, and malignancy. The reason behind this is their immunosuppressive nature and high cost.

Vitamin K2 is a bonus alternative as it can inhibit the production of TNFα, is safe and economical, making it the best choice for the treatment of psoriasis.

Psoriasis Frequently Asked Questions (FAQs)

I’ve been asking by many patients while treating psoriasis. So i write here frequently asked question by patients.

1) What is the success rate you’ve seen from this program in curing Psoriasis?

With the use of ointment, about more than 90% of the lesions disappeared. It is used for symptomatic treatment and cannot cure internal problems, but it improves social life significantly. Without the intake of medicines (Cepharanthine/ Erythrocin), and supplements (Shell Ginger/ other), the symptom might reappear anytime soon.

With Cepharanthine, Erythrocin, Shell Ginger, and other supplements, you can be free from psoriasis for a year or more. After that, we cannot predict the duration it takes to be free from psoriasis as it depends upon numerous factors, particularly mental stress. Proper diets, low-stress levels, and exercise reduces the recurrence rate by less than 30%.

2) How much does the psoriasis treatment cost?

PS(1) 50 g: ¥4200
PS(1) 100 g: ¥7140
MAS (1) 50 g: ¥4200
MAS (1) 100 g: ¥7140
MA(1) 50 g: ¥4200
Erythrocin (64 tablets for a month): ¥3520
Cepharanthin (120 tablets for a month): ¥3960
Oil Paper (100 sheets): ¥1600
Bio-Three (60 packs for a month): ¥1380
Minimum Shipping Cost: ¥1400 (to Asia), ¥2000 (North America, Australia, New Zealand), ¥2200 (Europe), ¥2400 (South America, Africa)
Consultation: Free, if on the Internet.

One US dollar ($) is 105 ～115 Japanese yens(¥). It depends on the exchange rate of the day. Therefore, for exmaple, PS(1) 50g costs $36.5 ～$40.

3) Do these pills and supplements have to be taken forever?

You don’t need to take them forever!

Erythromycin: Take for at least 12 weeks (about 3 months).
Cepharanthine: At least for 6 months. If possible, for 12 months.
But if recurrence occurs, for example, after one year, it is again recommended to take them for 3 more months.
Biotin: 6 months at least.
Probiotics: 6 months at least.
For Zinc, Copper, Selenium: For 3 to 6 months.
Take Omega-3 Unsaturated Fatty Acid, Inositol, Magnesium, Shell Ginger for at least half a year.

These natural supplements for psoriasis are effective for “Maintenance Therapy” of psoriasis. Moreover, it aids in preventing cancer, cardiovascular diseases, cerebrovascular diseases, rheumatoid arthritis, depression, etc.
I’ve been taking these supplements for more than ten years to maintain my general health. Hence, I recommend them for a longer duration.

4) Are there any of the small side effects I should be aware of with the two pills -- Cepharanthine and Erythrocin?

I’ve not witnessed any adverse side effects caused by these two medicines. Except one of my patients complained of abdominal bloating after taking Cepharanthine. I advised him to discontinue the medication. If any symptom appears after taking medicine, please consult your doctor.
Erythromycin (Erythrocin®)
Contraindications: If you are taking the following drugs, please don’t take Erythromycin.
Ergotamine tartrate / anhydrous caffeine / isopropylantipyrine / dihydroergotamine mesylate / Pimozide / Asunaprevir

Attention: If you are on one of the following medications, please consult your doctor before using Erythromycin along with the medicines.
Antiarrhythmic drug/Warfarin potassium/Theophylline/Aminophylline hydrate/Cyclosporine/Crolimus hydrate/Digoxin (Lanoxin)/Felodipine (Plendil,Renedil)/Valproate (VPA) (to treat epilepsy)/Midazolam/Carbamazepine(Tegretol)/Colchicine/Simvastatin/Atorvastatin(Lipitor)/Pitavastatin/Blonanserin/Ebastine/Edoxaban/Zafirlukast/Ritonavir/Cimetidine(Tagamet)/any anti-cancer drugs.

Caution: If you are on Calcium Channel Blocker (such as Amlodipine) for lowering your blood pressure, please avoid taking Erythromycin. It is because the combination of Amlodipine and Erythromycin may lead to hypotension.
Azithromycin is a macrolide antibiotic and is safe with Amlodipine. Also, macrolides are very important in the treatment of psoriasis. Thus, if you are currently under the medication of CCB, Azithromycin is the most suitable choice. But its potency is less than that of Erythromycin.

Patients often ask, “If I have been taking Erythrocin, an antibiotic for three months, are the side effects unsafe?”. The answer is that it is generally not dangerous unless you have severe disease. For example, Erythrocin is prescribed in cases like COPD (Chronic Obstructive Pulmonary Disease) continuously for one year. If we compare the side effects, the side effects of erythromycin are pretty minimal as compared to steroid pill/immunosuppressants such as Methotrexate, biologics such as ustekinumab (Stelara).

Even so, if any symptoms appear with Erythrocin (or Azithromycin), you should immediately stop it and consult your doctor.

Cepharanthine (Cepharanthin®)

There are no contraindications observed with Cepharanthine yet.

5) How much do I need the ointment?

It depends upon the size and number of plaques or eczema. So, it is not possible to say how much you need it. But for mild cases, usually, 50 g/month is enough. After the lesion disappeared, you don’t need it till relapse.

6) What dietary recommendations and foods to avoid with psoriasis?

There are certain foods to avoid with psoriasis, but the one-word answer for this question is becoming a vegetarian!! I can understand that for many, this diet is hard to adopt. Still and all, try to avoid animal products such as meat, milk and cheese, and whey as much as possible.

Looking through history, about 150 years ago, when western civilization was unknown in the east, people did not consume meat as Buddhism prohibited meat-eating and the killing of animals. Psoriasis was foreign in the east at that period. After the influence of Western culture, psoriasis began to emerge in Japan but, it is not as prevalent as in the US and Europe. The prevalence of psoriasis in Japan is 2 to 3 of 1000 people and 2 to 3 out of 100 people in the US. The prevalence rate is ten times higher in the United States. It is not due to genetics but rather because of diets.

Since the diet plays a vital role in curing several ailments, it is necessary to find out what kind of food triggers psoriasis in your case. As psoriasis rarely occurs in strict vegetarians., the best and cheap treatment of psoriasis is to become a vegetarian.

Adopting a vegetarian diet can reduce the symptoms in three years. Some patients try a low carbohydrate diet. But a low carbohydrate diet contains excess lipids and protein, which worsen psoriasis.

Q. If a high carbohydrate diet is unhealthy for psoriasis, why do the Americans suffer more than the Japanese?

A. Rice, a rich source of carbohydrates, is the staple food of Japan. Undoubtedly, an excess amount of carbohydrates is harmful to psoriasis, but excess lipid is even worse. By seeking a proper diagnosis of your condition, you can find the best psoriasis treatment.

* Periodic Fasting: You can practice it even once in a half year. It can give a good rest to your intestine, helps for detoxification, and improve the condition of psoriasis soundly. You can either visit a clinic offering a fasting course or can easily find it on the internet. Please do not practice it without consultation.

Additional Notes for Psoriasis Treatment Guidelines

Iron
There is an association between the metabolism of iron and psoriasis. When anemic patients with psoriasis take iron supplements, their condition deteriorates, as red blood cells contains iron. You must stop taking unnecessary iron supplements in such cases. It also explains why the symptoms ease when a psoriasis patient gets phlebotomy (bloodletting).

Please don’t take excess vitamin C supplements, as it stimulates the absorption of iron.

Probiotics
Probiotics improve digestion by increasing good bacterias and crowding out harmful bacterias in our gut.

Intestines are the largest immune system organ in the human body. Here, many hair-like villi occupy the small intestine with Payer’s patches. These patches have a crucial role in monitoring the immune system. Besides, our gut is known as the second brain due to its connection with the brain. Together, the brain and the intestine control our emotions, stress, cravings, and sleep.

It explains the importance of maintaining the intestinal environment to maintain a healthy state. The severe symptoms of psoriasis, caused by extreme stress and anxiety, can only be resolved by ensuring the good health and functioning of the intestine.

We use a preparation called Bio-Three. It is the trade name of a probiotic product, which contains three active strains of host-friendly bacteria, E.faecalis T-110, C.butyricum TO-A, and B.mesentericus TO-A. Research has shown that the combination of these three bacteria provides optimal synergistic effects.

For more details, please open http://www.bio-three.com/. It is the website of the manufacturer, but it might not be available in your country. If so, please find any suitable probiotics on the internet. You may have to try three or four different probiotics until you find the best one that suits your intestine.

* Also, try to eat one apple a day. The pectin of the apple has dietary fiber and helps in maintaining a healthy environment in the intestine.
* Ayurvedic medicine recommends cleaning our tongue because it helps to improve your gut flora. Please clean your tongue with a tongue cleaner twice a day. You can find a tongue cleaner easily on the internet or in a general store.

Detoxification
Detoxification is necessary to eliminate substances like heavy metals, toxic chemicals, artificial food additives, fragments of medicines, viruses, bacteria, etc., that cause psoriasis.

It is a great traditional system of medicine, including classical Chinese, Ayurvedic, and Tibetan medicine. According to the conventional method, toxins collected in the body undergo detoxification before prescribing therapeutic medication. In contrast, the modern practice provides prescriptions to patients with no prior detoxification.

One of the best ways of detoxification is taking a sauna (thermal bath), especially one using far-infrared rays. In this method, toxic substances excrete through sweat. Yet, one should not take saunas more than three times a week.

Bloodletting (phlebotomy) is also an effective way of detoxification. A warning, which may seem obvious, but is critical anyway, is never to undertake phlebotomy on your own. Only trust experienced health professionals to carry out the process. Please have a look at this: https://en.drmakise.com/shaketsu/.

* Drink plenty of water: You should drink at least 1- 2 liters of water per day, preferably in the morning. Water detoxifies many toxic matters that intensify psoriasis. But if you have a kidney problem, please consult your doctor about the safe level of water intake.

Ultraviolet (UV) Light
Solar UV light stimulates the production of vitamin D, which is necessary for the cure of psoriasis. Vitamin D minimizes the scaling of the skin by decreasing the overproduction of skin cells. Still, sunbathing near the window is not an effective method. The best way is to stay under the natural rays of the sun. It may take several weeks to see an improvement in your psoriatic lesions. Some people even travel to a tropical zone, an approach worth trying.

UV blood irradiation therapy also uses UV light, today commonly known as photoluminescence. It is a modern technique to treat diseases, including psoriasis, and is safe from adverse side effects.

Go to bed early
Sleep is one of the overlooked aspects of maintaining good health. You should go to bed at least by 11 pm, and if you go to bed later than midnight, your psoriasis can never get cured.

The growth hormone secretes from the pituitary gland between 11 pm to 3 am (3 hours after you fall asleep). Late sleeping habits can hinder the release of the growth hormone and impact skin damage. You know well that the human growth hormone is flaunted very much as an anti-aging supplement. Some anti-aging clinics offer injections of growth hormones, but the best way is to go to bed earlier. Note that the growth hormone gets secreted even if you are 80 years old or more.

When the blood glucose level is high, the pituitary gland cannot secret growth hormones sufficiently. Thus, do not go to bed at least 2 hours after dinner.

Caution
If you feel joint pain, stiffness, or swelling along with the skin symptoms of psoriasis, please consult your doctor first. You might be suffering from Psoriatic Arthritis, and you may have to take immunosuppressants such as Methotrexate immediately to avoid deformation of joints.

Concluding remarks

I have treated many people in Japan with this approach for the treatment of psoriasis. Even though psoriasis is a chronic skin disease, its symptoms can be alleviated and even cured by proper care and supervision. Using ointments for psoriasis is one of the best ways to relieve the symptoms of psoriasis. The origin of this disease is due to viruses that infect skin cells and affects the immune system.

Hence, the inactivation of viruses with oral medications, use of ointments, and maintenance therapy of minerals and vitamins can treat psoriasis efficiently and effectively. If you practice proper care, guidance, medicines, and diet, you can even prevent relapse of this disease.

The post Supplements, Medicine and Ointment for Psoriasis: Effective and Unique Treatment From Japan appeared first on STG Makise Lifeup USA.

Stem Cell

CustomerTeam — Wed, 25 Mar 2020 06:06:42 +0000

What is Stem Cell?

A Stem cell is an undifferentiated cell that differentiates to become any type of cell and from there further sub-divides. Scientists have recently utilized stem cells in regenerative and rejuvenative medicine. Stem cells transplanted into damaged human bodies will eventually contribute to a “De-Hospitalized Society”. The society has less drugs and less hospitals than now.

Stem cell Types:

ES Cell (embryonic stem cell)
iPS Cell (induced pluripotent stem cell)
Adult Stem Cell

Let’s survey historical aspects of stem cells.

I. Epigenetic Landscape

Cells develop from only one fertilized egg — zygote. A “Totipotent Cell” with the ability to differentiate into more than 220 cell types. except placenta. But its Totipotency, (which represents the cell with the greatest differentiation potential) is not retained during all the various stages of cell sub-division.

The first sub-division provides 2 Totipotent cells. The second 4 cells, retain Totipotency But the following 8 cells no longer retain the ability to differentiate into all types of cells. Further sub-divisions differentiate into specialized cells such as fibroblasts, erythrocytes, nerve cells, intestinal mucosal epithelial cells and pancreatic islet cells, etc. but following 6 to 7 full further cell sub-divisions (about 5 days after fertilization), the embryo becomes a “Blastocyst” and possesses “Inner Cell Mass (ICM) “

ICM cells can differentiate into any cell type, except placenta — pluripotency. 3 weeks after fertilization, the cells of the inner cell mass differentiate into ectoderm, mesoderm, and endoderm. In the 1950s, this differentiation was thought to be irreversible, being described as a ball rolling down a hill and technically known as ” Epigenetic Landscape”.

This was until 1962 when John Gurdon created clone frogs and then in 1996, Ian Wilmut created “Dolly ” the cloned sheep. Scientists had previously thought stem cells could not have pluripotency once dispersed into a specialized cell. however, in nature, even once differentiated, some cells can again differentiate and this phenomenon is known to science.

II. Cells of Planaria

The stem cells of humans have a limited ability to differentiate. But for example, Planaria that is a small flatworm living in rivers has an amazing ability to differentiate into any organs, even into itself. When it is chopped into 3 fragments like a picture, each fragment regenerates to a perfect Planaria. There is a record that 1/279 fragment of one Planaria regenerated to perfect Planaria. When Planaria grows to a certain size, it divides itself to two fragments. And each fragment grows to a perfect Planaria. For Planaria, division and regeneration are mechanisms for reproduction. But under some circumstances, Planaria chooses sexual reproduction.

III. Cells of Plant

A Plant can regenerate itself from one already differentiated cell. An Enzyme mixture of Cellulase Onozuka R-10 and Macerozyme R-10 dissolves tobacco plant (Nicotiana tabacum) leaf cell walls, and cells become leaf protoplasts (= cell without cell walls). When protoplasts are cultivated under appropriate condition, the protoplasts grow to a seedling plant through plant callus (= mass of unorganized parenchyma cells). When the seedling plant is planted in soil, it grows to a perfect tobacco plant.

Two British scientists proved biological technique could change Epigenetic Landscape.

IV. Frog of John Gurdon

Gurdon created cloned frogs.

He destroyed the nucleus of Frog A ovum by ultraviolet rays.
He removed the intestinal cell “tadpole nucleus” of Frog B which was transplanted into Frog A’s ovum, the nucleus of which was already destroyed by ultraviolet rays. This new ovum became Clone Embryo B which grew into Frog B’s tadpole was later to become cloned adult Frog B.

V. Ian Wilmut’s “Dolly” The Cloned Sheep

Wilmut used a cell nucleus which had been differentiated in the mammary gland.

He took out the ovum from Sheep A, and removed its nucleus.
From Sheep B he removed the mammary gland cell nucleus.
Into the ovum of Sheep A, he transplanted the nucleus of Sheep B.
The Sheep A ovum was then electrically stimulated.
The stimulated cell divided to became the cloned embryo of Sheep B.
The cloned Sheep B embryo was transplanted into the uterus of Sheep C.
Sheep C gave birth to Cloned Sheep B. This sheep was named “Dolly”.

VI. ES Cells(embryonic stem cells)

Human embryos reach “Blastocyst” about 5 days’ post-fertilization. The Blastocyst possesses an “Inner Cell Mass (ICM) ” In 1981 Martin Evans succeeded in culturing mouse ICM cells. These cells are capable of propagating themselves indefinitely in an undifferentiated state, and they can differentiate into any type of cell except placenta. These cells are pluripotent and known as Embryonic Stem Cell (ES Cells).
James Thomson created ES Cells from Monkey embryo in 1995 and later in 1998 created ES Cells from a human embryo. However, research into ES Cell needs further study due to an ethical dilemma, that in order to isolate inner cells from the blastocyst, the blastocyst is destroyed, so is the embryo at the pre-implantation stage to be considered human? and even if not, do we have the right to destroy human potential growth.

VII. iPS Cells (Shinya Yamanaka)

The ethical issue of ES Cells can be by-passed by using Induced pluripotent stem cells. The iPS cell is a pluripotent stem cell which can be generated directly from adult cells, not from human embryos, and in 2006, Shinya Yamanaka and his team in Kyoto University created iPS cells from mouse fibroblasts.

He hypothesized that the genes playing a pivotal role in the function of ES Cells could induce an embryonic state in adult cells. But how many are the genes? The human has 20 – 25 thousand genes. Yamanaka researched and found 24 genes which were important for the characteristic protein of human ES Cells, and then used retroviruses to deliver all 24 genes into mouse fibroblasts, and the fibroblasts were able to propagate indefinitely. These iPS Cells were pluripotent like ES Cells.

Yamanaka removed one factor at a time from the 24 factors to identify the necessary genes for reprogramming and by this process he identified 4 factors — Oct3/4, Sox2m Klf4, and c-Myc – named the “Yamanaka Factors”, and Later he found c-Myc was not needed for reprogramming, but without c-Myc the process took longer and was inefficient.

A strong concern of the iPS researchers was if iPS Cell differentiation caused cancerous cells. But this issue has almost been resolved completely through rigorous study. And many clinical human applications are now carried out in Japan. For example, in 2014 retina transplantation by iPS Cells was successfully carried out for age-related macular degeneration. And cells did not differentiate into cancer cells. In my next page, I write more about these applications.

iPS Cells are useful not just for regenerative medicine but for drug discoveries or development. Because it is very easy for researchers to recreate special cells which cause special diseases, in a petri dish — Alzheimer’s disease, Parkinson’s disease, ALS (Amyotrophic Lateral Sclerosis), Schizophrenia.

For example, “Achondroplasia” which is caused by a mutation in fibroblast growth factor receptor 3. This is a common cause of dwarfism. Researchers made iPS Cells from skin fibroblasts of 3 patients with achondroplasia then allowed the iPS Cells to differentiate into chondrocytes over 2 to 3 weeks. Chondrocytes in the petri dish secreted about themselves an extracellular matrix which is characteristic of chondrocytes and made a mass.
Compared to the chondrocytes of healthy people, these patient’s chondrocytes grew slowly, and the researchers tried thousands of drugs one by one to cure the abnormal chondrocytes of the petri dish specimens. Then finally, and with much surprise, they found the “Statin drug” was effective and able to cure the abnormal chondrocytes of achondroplasia patients. Why surprise? Because Statin drugs are for lowering cholesterol, and nobody expected cholesterol-lowering drugs to be effective against achondroplasia.

In the next pages, I explain in more detail about practical and clinical uses of iPS Cells.

The researchers of iPS Cells were most afraid of differentiation of iPS Cells into cancer cells. But now this problem has been almost solved by rigorous studies. And many clinical applications for humans are being done in Japan. For example, in 2014 transplantation of iPS Cells of retina was successfully done for age-related macular degeneration in Japan. The cells have not differentiated into cancer cells. In the next page, I write more about the applications.

iPS Cell is very useful not only for regeneration medicine but also for drug discovery or drug development. Because it is very easy for researchers to make the special cells that cause the special diseases — Alzheimer’s disease, Parkinson’s disease, ALS (Amyotrophic Lateral Sclerosis), Schizophrenia — in petri dish.

VIII. Adult Stem Cell (Somatic Stem Cells or Tissue Stem Cell)

Adult Stem Cells are undifferentiated cells found throughout the body such as in bone marrow, and umbilical cord blood, and the mammary gland, and the surface of the small and large intestines, the adipose tissue, the lining of the nose, the testicles, and the hair follicle, between the basement membrane and the sarcolemma of muscle fibers (Satellite Cells), etc.

These cells are multipotent cells that have less ability to differentiate into specialized cells than pluripotent cells. The adult stem cell from the bone marrow, called Hematopoietic Stem Cell (HSC), was discovered in the 1960s by two Canadian biologists, James Till, and Ernest McCulloch, and has been used clinically to cure various blood diseases, such as leukemia, malignant lymphoma, multiple myeloma, etc. Clinically a very important cell. But for regenerative medicine, it needs much practical work to obtain stem cells from bone marrow and requires general anesthesia, however, scientists recently have found it easier to obtain these cells.

This is by ASC (adipose-derived stem cell) from our fat. The first scientific reports on ASC were made by an American scientist, Patricia Zuk (UCLA), in 2001. She reported the presence of mesenchymal stem cells in the fat tissues, and as they have a faster growth rate, these cells are expected to be advantageous for regenerative medicine.

ASC can differentiate into muscle, bone, cartilage, liver, adipose cell (lipid cell). And besides the advantages as stem cell, ASC secrets exsosome (nano-size particles) that contain enzymes which dissolve beta-amyloid of Alzheimer’s disease. The efficacy is 8 times more potent than the enzymes secreted by the exssome of the bone marrow.

ASC is now aggressively researched in Japan for practical uses. It will be used to treat many diseases such as Alzheimer’s, Parkinson’s, and diseases of the liver and kidneys, and periodontal disease, and more. For example, please see the video:

In Japan, Tottori University Medical School researchers have established the technique of breast reconstruction by ASC after mastectomy due to cancer. They operate and inject ASC into the patient’s depressed breast. The breast recovers to the original shape within three months. This is not silicon, but the patient’s own cells. Quite natural. No rejection. The cost of this treatment will be covered by health insurance within three years in Japan.

Doctors at the Nagoya University Medical School use ASC against urinary incontinence stress. The sphincter function of the urethra often weakens due to aging, delivery, and some bladder diseases. ASC is injected around the patient’s urethra to strengthen the smooth muscle.

However, some side effects may occur by use of ASC. For example, male prostate hyperplasia and female endometriosis. Issues not studied in depth. So for now until the side effects have been dealt with, we should wait for general anti-aging treatments.

IX. Direct Reprogramming. “A Newer Approach”

Recently it was found possible to induce, directly from somatic cells, not only iPS but nerve cells, hepatocyte cells, myocardium cells, cartilage cells, and many varied cells by introducing the specific key transcription factors in cell differentiation, which means that through by-passing of pluripotent stem cells it is possible to induce differentiated specific cells from somatic cells. This is called “Direct Reprogramming”, and the most exciting research for example is: myocardial reprogramming in vivo, where Doctors inject patient’s fibroblasts with transcription factors to the infarcted lesion of the heart.
There the fibroblasts differentiate into myocardium (heart muscle). So, simple and quick. And this regenerative medical technique is under development mainly in Japan and the United States and as this technique is established, lots of heart surgeries will become obsolete and this is also true of brain surgery. The numbers of hospitals will eventually reduce and cost of time-consuming surgeries will lower and this will lead on to a “De-Hospitalized Society”.

Conclusion

For a basic understanding of stem cell mechanisms: ES Cell is studied along with iPS Cell and ASC. But ES Cell has an ethical dilemma and this issue shall not be overcome by science. So, it cannot be used for the treatment of human diseases. Direct Reprogramming: Wonderful technology. But it may take 10 or 20 years more to accomplish it. Therefore, at this moment, iPS Cell and ASC are most realistic medical tools for those who are suffering from degenerative diseases and wish rejuvenation.

PRACTICAL APPLICATIONS OF IPS CELLS

Stem cells and induced pluripotent stem cells (iPS or iPSCs) have found their usage in a large number of human welfare such as drug development, toxicity tests, organ/ tissue regeneration, and repair etc. Induced pluripotent stem cells (iPSCs) could also be of great use in studying molecular mechanism of many diseases. Many diseases have been modeled by using iPSCs for better understanding of their etiology which may be further utilized for developing putative treatments for these diseases. The use of iPSCs may eliminate the chances of immune rejection as patient-specific cells may be used for transplantation in various engraftment processes. Moreover, iPS technology has been employed in various diseases for disease modeling and gene therapy. The technique offers benefits over other similar techniques such as animal models. Many toxic compounds (different chemical compounds, pharmaceutical drugs, other hazardous chemicals, or environmental conditions) which are encountered by humans and newly designed drugs may be evaluated for toxicity and effects by using iPSCs. The applications of stem cells and especially iPSCs in regenerative medicine, disease modeling, and drug discovery are enormous and should be explored in a more comprehensive manner.

In this web presentation you read 6 major applications of Stem cells and IPS cells:

Uses in Regenerative medicine (tissue/organ regeneration)
Uses in Disease modeling
Uses in Drug Discovery / Development
Uses in Drug testing/ Toxicity Testing
Uses in Tissue repair
Uses in Gene Therapy

Advantages of iPS technology over other conventional therapies:

The ethical issues are avoided by the use of iPSCs
iPSCs have solved the controversy over the destruction of embryos associated with the use of ES Cells (embryonic stem cells).
Reduced chances of immunorejection
iPSCs are generated from the somatic cells of one’s own body and hence there is no risk of immunorejection of these autologous cells.
Throughput screening for predicting toxicity/therapeutic responses of newly developed drugs
The concept of using iPSCs to predict toxicology and therapeutic responses of drugs in based on the property of iPSCs to continuously self- renew which make it possible to generate libraries and their ability to give rise to all types of body cells.
Lowering the overall cost and risk of clinical trials
The cost used for the clinical trials could be reduced by using iPSCs to provide the toxicity details of the drug by different cytotoxicity assays. The use of iPSCs for these tests may cut the cost associated with providing animal models which will ultimately decrease the overall costs of the clinical trials.
Development of a personalized approach for administration of drugs
As, iPSCs are derived from individual patients, these offer scientists an opportunity for modeling diseases on a patient-by-patient basis. This enables screening the genomic differences between individuals that may help in the progression of disease, and the screening of pharmacological agents to find the ideal one for each individual.
Gene targeting and correction technologies (gene therapy)
Reprogramming of somatic cells from any genetic background to iPSCs has allowed the generation of cell lines possessing disease-causing mutations.

USES IN REGENERATIVE MEDICINE

The application of iPSCs for generating tissues and organ grafts can solve many problems in organ transplants and improve the quality of life for millions of patients. iPSCs can be directed to generate specific cell types and can be used to replace ailing or degenerating tissues. The greatest advantage of this technique is that it overcomes graft-to-host incompatibility. It is for this reason that graft rejection by the hosts immune system decrease significantly. There are about 90,000 patients in the US transplant-waiting list, who need medical assistance, which can be addressed by stem cell technologies.

Kidney Regeneration

iPSCs technology can be used to transform terminally differentiated skin cells into kidney organoids which are functionally and structurally similar to those of kidney tissue in vivo. During kidneys healing process, a progenitor stem cell needs to become 20 types of cells, required for waste excretion, pH regulation, and restoration of water and electrolytic ions. The ex vivo kidney organoids are similar to fetal first-trimester kidneys for their structure and physiology. They can also be served as model for nephrotoxicity screening of drugs, disease modelling, and organ transplantation. However, there are many hurdles coming to the point of generation of fully functional kidney that can be dreamed for the near future.

Liver Regeneration

iPSC-Liver buds have been developed from a mixture of three different kinds of stem cells, i.e., hepatocytes (for liver function) coaxed from iPSCs; endothelial stem cells (to form lining of blood vessels) from umbilical cord blood; and mesenchymal stem cells (to form connective tissue). This approach is like mimicking the fetal development and formation of a complex organ. In one experiment, after growing in vitro for a few days, the liver buds were transplanted into mice where the ‘liver’ quickly connected with the host blood vessels and continued to grow. It also performed regular liver functions including metabolizing drugs and producing liver-specific proteins. Further studies will monitor the longevity of the transplanted organ in the host body (ability to integrate or avoid rejection) and whether it will transform into tumors. Using this method, cells from one mouse could be used to test 1,000 drug compounds to treat liver disease and reduce animal use by up to 50,000.

Visual acuity Regeneration

Loss of neurons in age-related macular degeneration (ARMD) is the common cause of blindness. At preclinical level, transplantation of iPSCs derived neuronal progenitor cells (NPCs) in rat limits progression of disease through generation of 5-6 layers of photoreceptor nuclei, restoring visual acuity.

Y. Tsai, B. Lu, B. Bakondi et al., “Human iPSC-derived neural progenitors preserve vision in an AMD-like model,” STEM CELLS, vol. 33, no. 8, pp. 2537–2549, 2015.

Neurons Regeneration

The high order brain functions, like emotions, anxiety, sleep, depression, appetite, breathing heartbeats, and so forth, are regulated by serotonin neurons. Generation of serotonin neurons occurs prior to birth, which is post-mitotic in their nature. Any sort of developmental defect and degeneration of serotonin neurons might lead to neuronal disorders like bipolar disorder, depression, and schizophrenia-like psychiatric conditions. Manipulation of signaling in human iPSCs in defined culture conditions leads to an in vitro differentiation of iPSCs to serotonin-like neurons. These iPSCs-neurons primarily localize to rhombomere 2-3 segment of rostral raphe nucleus, exhibit electrophysiological properties similar to serotonin neurons, express hydroxylase 2, the developmental marker, and release serotonin in dose and time dependent manner. Transplantation of these neurons might cure from schizophrenia, bipolar disorder, and other neuropathological conditions.

J. Lu, X. Zhong, H. Liu et al., “Generation of serotonin neurons from human pluripotent stem cells,” Nature Biotechnology, vol. 34, no. 1, pp. 89–94, 2016.

Placenta Regeneration

Placenta, the cordial connection between mother and developing fetus, gets degenerated in certain pathophysiological conditions. Nuclear programming of OCT4 knock-out (KO) and wild type (WT) mice fibroblast through transient expression of GATA3, EOMES, TFAP2C, and +/− cMYC generates transgene independent trophoblast stem-like cells (iTSCs), which are highly similar to blastocyst derived TSCs for DNA methylation, H3K7ac, nucleosome deposition of H2A.X, and other epigenetic markings. Chimeric differentiation of iTSCs specifically gives rise to hemorrhagic lineages and placental tissue, bypassing pluripotency phase, opening an avenue for generation of fully functional placenta for human.

H. Benchetrit, S. Herman, N. Van Wietmarschen et al., “Extensive nuclear reprogramming underlies lineage conversion into functional trophoblast stem-like cells,” Cell Stem Cell, vol. 17, no. 5, pp. 543–556, 2015.

Lungs Regeneration

Degeneration of other organs and tissues also has been reported, like degeneration of lungs which might occur due to tuberculosis infection, fibrosis, and cancer. The underlying etiology for lung degeneration can be explained through organoid culture. Coaxing of iPSC into inert biomaterial and defined culture leads to the formation of lung organoids that consisted of epithelial and mesenchymal cells, which can survive in culture for months. These organoids are miniature lung, resemble tissues of large airways and alveoli, and can be used for lung developmental studies and screening of antituberculotic and anticancer drugs.

B. R. Dye, D. R. Hill, M. A. Ferguson et al., “In vitro generation of human pluripotent stem cell derived lung organoids,” eLife, vol. 4, Article ID e05098, pp. 1–25, 2015.

Chronic Wound Healing

Chronic wounds are rarely seen in otherwise healthy individuals; they are often associated with diabetes, obesity or old age. It has been estimated that 1-2% of people in developed countries suffer from chronic wounds in their lifetime [i].Current methods of wound management are palliative, but their ineffectiveness for complex wounds is an ongoing clinical problem. Healthcare systems are in desperate need of alternative therapies. Stem cells/ iPSCs are known to tremendously influence normal cell and tissue repair/regeneration, which is why a large proportion of research focuses on stem cells as the answer to treating chronic wounds. Self-renewing characteristics and multipotent differentiation potential of stem cells make them ideal candidates for the treatment of chronic wounds. Stem cell-based therapies bring about their effectiveness via a number of mechanisms. Stem cells can differentiate into new cells, secrete trophic factors, promote angiogenesis, modulate the immune system, improve wound closure, and also help in the development of new extracellular matrix (ECM).

F. Gottrup. A specialized wound-healing center concept: the importance of a multidisciplinary department structure and surgical treatment facilities in the treatment of chronic wounds. The American Journal of Surgery, vol. 187, no. 5, pp. S38– S43,2004.
http://www.fiercebiotech.com/r-d/researchers-repair-retinas-mice-virus-free-stem-cells

DISEASE MODELLING

The use of stem cells especially iPSCs for disease modeling is based on the fact that these cells are capable of self-renewing and that these cells can differentiate into all types of cells of the human body which can be utilized for the preparation of different disease models to study those diseases. Moreover, a patient-specific iPSC could be of enormous use as far as development of specific therapeutics regimen/drug is concerned. By combining 3D culture with extracellular matrix proteins, in-vivo microenvironment can be mimicked. iPSCs have helped out in studying various mechanisms that play role in different diseases, a few have been described below.

The following findings from modeling different diseases help out in knowing the molecular mechanisms underlying the disease better, which ultimately carries the work forward to knowing the disease better for the development of a treatment.

Neurogenerative diseases

Parkinson’s Disease (PD) is a very common neurodegenerative disease, in which, dopaminergic neurons of substantia nigra (a structure in midbrain) get lost and formation of Lewy’s bodies (inclusions in the cytoplasm of neurons all over the body) occurs. Treatment of this disease had not been possible due to the reason that by the time, Parkinson Disease gets clinically manifested, the neurons have already lost, which makes it very difficult to study the underlying mechanisms of Parkinson disease so as to develop a treatment of it. In such a situation, iPSCs can be used and experiments have also been carried out in this aspect. Devine et al. developed iPSCs from fibroblasts taken from a Parkinson disease affected person possessing triplication of Synuclein gene by the transduction of four basic transcription factors. These iPSCs were then directed to differentiate into dopaminergic neurons in vitro for the study of Parkinson Disease. Another research by Professor Atsushi Takahashi of Kyoto University iPS cell research institute transplanted nerve cells made from human iPS cells to Parkinson’s disease monkey on August 30, 2017, claimed to alleviate the Parkinson disease symptom (hand tremor). The research results were published in English Science Journal, Nature (electronic version). The research team created nerve cells that emitted dopamine from iPS cells based of Parkinson’s disease patients. This was transplanted into the brain of cynomolgus monkeys reproducing the symptoms of Parkinson’s disease. Observing the one year course after transplantation, the symptoms of Parkinson ‘s disease such as trembling and reduced exercise ability were alleviated over time.

Devine, Michael J., et al. “Parkinson’s disease induced pluripotent stem cells with triplication of the α-synuclein locus.” Nature Communications 2 (2011): 440

Alzheimer’s Disease

Recent preclinical evidence suggests that stem cells can be used to treat or model Alzheimer’s Disease. The mechanisms of stem cell-based therapies for Alzheimer’s Disease include stem cell-mediated neuroprotection and trophic actions, anti-amyloidogenesis, beneficial immune modulation, and the replacement of the lost neurons. iPSCs have been recently used to model investigate sporadic and familial Alzheimer’s Disease pathogenesis, and screen for anti- Alzheimer’s Disease, drugs.

Fan, Xiaotang, et al. “Stem‐Cell Challenges in the Treatment of Alzheimer’s Disease: A Long Way from Bench to Bedside.” Medicinal research reviews 34.5 (2014): 957-978.

Down’s syndrome

Briggs et al. used iPSCs for the identification of molecular networks that drive the different aspects related to pathogenesis in Down’s Syndrome. iPSCs in combination with microarray and RNA sequencing technology, can be used to generate phenotype-genotype maps of complex diseases by linking various defects with phenotypes, like in Down’s Syndrome using Chromosome engineering of Down Syndrome-iPSCs

Briggs, James A., et al. “Integration‐free induced pluripotent stem cells model genetic and neural developmental features of down syndrome etiology.” Stem Cells 31.3 (2013): 467-478.

Study of Prostate and Urinary Tract diseases

Moad et al. used human prostate and urinary tract cells for the formation of iPSCs and further for studying the mechanisms that regulate the differentiation of prostate and urinary tract cells. With their study, they reported the first successful reprogramming of bladder, prostate and ureter stromal fibroblasts into a pluripotent state and concluded that iPSCs generated from prostate and urinary tract had better efficiency of differentiation to cells of prostate and urinary tract as compared to iPSCs derived from skin fibroblasts which showed that organ of origin plays an important role in terms of efficiency of differentiation.

Moad, Mohammad, et al. “A novel model of urinary tract differentiation, tissue regeneration, and disease: reprogramming human prostate and bladder cells into induced pluripotent stem cells.” European urology 64.5 (2013): 753-761.

Other deficiency diseases – Various types of diseases which are caused by some deficiency have been studied by using iPSCs. Park et al. used iPSCs from patients of various diseases like Adenosine Deaminase Deficiency-related Severe Combined ImmunoDeficiency (ADA-SCID), Shwachman-Bodian-Diamond syndrome (SBDS), Gaucher disease (GD) type III for the study of disease models and drug discovery.


Disease/Syndrome	Becker type muscular dystrophy (BMD)
Causes	Mutation in dystrophin gene
Features	Loss of walking ability, but progression slower than DMD
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	Downs syndrome/trisomy 21
Causes	Trisomy of chromosome 21
Features	Cardiac and cognitive defects, premature Alzheimers disease and aging, dysmorphic facial features
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	Familial dysautonomia (FD) or Riley-Day syndrome
Causes	Autosomal recessive disorder caused by a single mutation in exon 20 in I-K-B kinase complex associated protein (IKBKAP) gene
Features	Dysfunction of small fiber sensory neurons
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	Childhood cerebral adreno leuko dystrophy (CCALD)
Causes	Mutation in ABCD1 gene
Features	Adrenal cortex, nervous system and testes get affected, leading to rapid cerebral demyelination and adrenocortical atrophy.
Cells used for iPSC generation	Skin fibroblasts


Disease/Syndrome	Rett’s syndrome
Causes	Classic form caused by loss-of-function mutation in Methyl-CpG-binding protein 2 (MECP2) gene on the X – chromosome, variants caused by mutations in FOXG1 or CDKL1 on chromosome 14 and X-chromosome, respectively
Features	Neurocognitive regression and autistic behavior
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	Duchenne type muscular dystrophy (DMD)
Causes	Biochemical and genetic defects in Dystrophin-glycoprotein complex
Features	Loss of walking ability
Cells used for iPSC generation	Tail tip fibroblasts (mouse)


Disease/Syndrome	Alzheimer disease
Causes	Duplication of amyloid β precursor protein (APP)
Features	Presence of neurofibrillary tangles and amyloid plaques in the brain
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	LEOPARD syndrome
Causes	Mutation in protein tyrosine phosphatase non-receptor type 11 (PTPN11) gene
Features	Increased failure of bone marrow, pulmonary fibrosis and cancer, oral leykoplakia, abnormal skin pigmentation and nail dystrophy
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	α1-antitrypsin deficiency
Causes	Mutation in α1-antitrypsin (A1AT) gene
Features	misfolded α1-antitrypsin gets aggregated in the endoplasmic reticulum
Cells used for iPSC generation	Dermal fibroblasts


Disease/Syndrome	Parkinson’s Disease (PD)
Causes	Familial forms caused by α-synuclein, ubiquitin carboxy terminal hydroxylase L1, parkin, DJ-1, putative serine threonine kinase 1 and leucine rich repeat kinase 2
Features	Loss in nigrostriated dopaminergic neurons in substantia nigra; presence of Lewy bodies
Cells used for iPSC generation	Dermal fibroblasts of patient with idiopathic PD


Disease/Syndrome	Huntington disease (HD)
Causes	CAG repeats (36 or more) in the first exon of htt gene gets expanded abnormally
Features	Degeneration in striatum and cerebral cortex
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	ALS or Lou Gehrig’s disease
Causes	Autosomal dominant mutation in superoxide demutase (SOD1)
Features	Death of motor neurons of the motor cortex, brain stem and spinal cord
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	Friedreich’s ataxia (FRDA
Causes	GAA trinucleotide repeat in the first exon of the frataxin gene gets expanded
Features	Accumulation of mitochondrial iron, specific enzymes in mitochondria become defective, sensitivity to oxidative stress increases, cell death mediated by free radicals
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	Lesch-Nhyan syndrome (carrier state)
Causes	Deficiency of hypoxanthine guanine phospho ribosyl transferase (HPRT)
Features	Over-production of uric acid, low or medium level of mental retardation, megaloblastic anemia is frequent
Cells used for iPSC generation	Dermal fibroblasts


Disease/Syndrome	Shwachman-Bodian-Diamond syndrome (SBDS)
Causes	Mutations in the Shwachman-Bodian-Diamond syndrome (SBDS) gene
Features	Exocrine pancreatic insufficiency, predisposition to leukemia, hematopoietic dysfunction
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	Gaucher’s type III
Causes	Deficiency of acid hydrolase, β-glucocerebrosidase, or glucosylceramidase
Features	Myoclonal epilepsy, nerve deafness
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	Generation of human prostate and urinary tract cells
Causes	NA
Features	NA
Cells used for iPSC generation	Human prostate and urinary tract cells


Disease/Syndrome	Adenosine deaminase deficiency-related severe combined immunodeficiency (ADA-SCID)
Causes	Defects in Adenosine deaminase (AD) gene
Features	Impaired development and functioning of T, B, and NK cells; complete absence of humoral and cellular immunity; recurrence of infections.
Cells used for iPSC generation	Bone Marrow derived mesenchymal cells


Disease/Syndrome	Type 1 diabetes mellitus (DM)
Causes	Progressive β-cell destruction
Features	Long term micro and macro-vascular complications.
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	Hemophilia A
Causes	Deficiency of factor VIII
Features	Decreased protein production, inefficient clotting of blood
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	Familial hypercholestrolaemia
Causes	Mutation in low density lipoprotein receptor (LDLR) gene
Features	Deficiency of LDL-receptor mediated uptake of cholesterol
Cells used for iPSC generation	Dermal fibroblasts


Disease/Syndrome	Spinal muscular atrophy
Causes	Mutation in survival of motor neuron 1 (SMN1) gene
Features	Paralysis, muscle weakness and often death
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	Hutchinson-Gilford progeria syndrome
Causes	Point mutations in lamin A
Features	Premature atherosclerosis, vascular smooth muscles gets degraded
Cells used for iPSC generation	Fibroblasts

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