Degenerative diseases are diseases remaining after the antibiotic victory over infectious diseases. The other important cause of injury and death is road accidents. The degenerative diseases are the result of cell death. Specialized cells meant to carry out special functions such as muscle or nerve die due to several reasons and are not replaced and this results in loss of function. The loss of function leads to the degenerative disease. A good example would be Parkinson’s disease. This disease is caused by death and degeneration of dopamine secreting neurons in the brain. Loss of dopamine secreting cells results in decreased levels of dopamine. Dopamine is needed for co-ordinated muscle movement. Parkinson patients show a characteristic tremor and inability to move their limbs and body in a coordinated manner. The present way to treat these patients is by giving -Dopa ,a precursor of Dopamine through an oral route. This is a very ineffective way of treating this disease and it invariably results in slow and painful death.

Though it was known that diseases involving the blood forming tissue, the bone marrow could be treated successfully by transplanting healthy bone marrow which was tissue matched , it was not known whether it could be extended to other tissues viz. brain. Bone marrow transplantations also showed that the successful cures were due to a special type of cell called stem cell which had the property of self renewal as well as differentiation into all the blood cell types.

It was in the last part of the 20th.century that Dr.Thompson from the University of Wisconsin, U,S.A. showed that the inner mass cells from the developing human embryo could be induced to act as stem cells with the potential to develop into each and every cell in the human body. He was not first to show this because it had already been shown in a mouse model. This discovery literally gave birth to regenerative medicine, since the stem cells could be used to regenerate cells lost due to death or decay. There was great hope for patients of Parkinson and other degenerative diseases. However, the hope was short-lived, since further research showed that the embryonic stem cell as they were called, had a great potential also to form tumors.

At this point, good news appeared in the bone marrow stem cell research. Patients who had undergone bone marrow transplantation for blood cell diseases showed that some of the stem cells had also given rise to tissues other than those of blood cell origin. This observation went against a well established dogma of developmental biology which stated that differentiation was a one way street and there was no going back i.e. stem cell from bone marrow had to give rise to blood cells and not to nerve or muscle.

Thus due to the dogma, adult tissue specific stem cells could not be used for regeneration of neurons, muscle or cartilage, even though experimental results showed otherwise. In the last ten years overwhelming evidence from clinical trials all over the world, including India have shown that tissue specific viz. bone marrow, adipose tissue and mesenchymal stem cells can and do regenerate muscle, cartilage, bone and neurons. The stem cell task force of the Indian Council of Medical Research the Government body which has to O.K ,the use of bone marrow for regeneration of cartilage etc.is still adamantly refusing to permit it except as an experimental therapy. Since the stem cells cannot be patented and only the process of enriching or cultivation is patentable resulting in very porous IPR which can easily be broken, no pharmaceutical or biotechnology company is willing to finance such trials. This has resulted in several doctors carrying out stem cell therapy without any documentation and validated SOPs. The nett result is fleecing of desperate patients. However, there are a few law abiding doctors and biotechnology companies who have carried out clinical trials and shown conclusively that regeneration of adult tissue is possible using adult tissue specific stem cells such as bone marrow. A large number of trials carried out in Japan, U.S.A and Europe also show the same results.

One of the first trials using autologous bone marrow enriched stem cells was for re-establishment of blood capillaries in Critical Limb Ischemia or Burger’s disease. Burger’s disease is a disease of tobacco smokers mainly India, Japan and south east Asia. Sufferers show loss of circulation in their lower limb due to narrowing of vessels and blood clotting. Loss of blood supply leads to cell death and resultant gangrene. The only way save these patients is amputation of the lower limb making these patients unable to make a living since, the patients are mostly laborers. In some cases a by-pass can be done to re-establish circulation and save the limbs. The trial conducted by Dr.K.R.Suresh, an eminent vascular surgeon at Sri Bhagwan Mahaveer Hospital, Bangalore, conclusively showed that revascularization was achieved in all most all patient’s of Burger Disease, when their own bone marrow enriched stem cells were injected into the muscles of their lower limb. The results were published in the Journal of Vascular Surgery. These results were substantiated by another similar study by another vascular surgeon Dr.Vijaya Raghavan from Chennai. Several other studies in Japan also support these findings.

Another trial conducted in Delhi by Dr.A. Suri, concerns treatment of diabetic foot ulcers using patient’s own bone marrow derived stem cells. Diabetic foot ulcer is very difficult to heal. This is because the blood vessels supplying blood to the ulcer area are destroyed and are not regenerated due to diabetes. No conventional treatment exists to treat these ulcers, which turn gangrenous, leading to amputation of the limb. In this study it was clearly shown that bone marrow stem cells can restore circulation and heal the ulcer. Several studies done abroad also support this finding.

A most promising trial to show that bone marrow / adipose tissue derived mesenchymal stem cells can regenerate the cartilage in the knee joint was conducted by Dr.Pradeep KIran,Columbia Asia Hospital, Bengaluru, in a sports injury. The results were very promising. This trial was followed by another trial by Dr.Rudraprasad and Dr. Deepak Rudrappa who showed that cartilage damage in Osteoarthritis could be reversed by bone marrow/adipose tissue derived mesenchymal cells in a large number of patients. These studies have been confirmed by laboratory studies which conclusively showed that mesenchymal stem cells from bone marrow/ adipose tissue could be differentiated into chondrocytes.

Mesenchymal stemcells are known to have immunomodulatory properties

Several studies in the United States of America has shown that these cells can be used to immunomodulate in clinical trials. A trial in New Delhi showed that mesenchymal stem cells could be successfully used to treat septic shock syndrome.A trial at Bangalore showed that mesenchymal stem cells can bring about decrease of RA factor in rheumatoid arthritis patients.

It is time now to convince the Government of India that Cellular Therapy is now ready to standard of care for several degenerative diseases listed above. There are several more such a Parkinson’s,stroke,multiple sclerosis ,alcohol induced liver damage and myocardial infarct where evidence is mounting from well trials abroad that bone marrow/adipose tissue derived stemcells can be a reliable tool for regenerative medicine. Unfortunately several other degenerative diseases cannot be treated as of now viz. Muscular Dystrophy, Chronic Kidney disease, Spinal cord injuries, since in these, degeneration is followed by SOS repair which makes it necessary to clear this scarification before stemcell implantation. Tissue Engineering approach is needed in treating some of the above listed diseases. Government funded institutions alone can carry out research and develop novel treatments involving the use of stemcells from bonemarrow/adipose tissue/umbilical cord /cord blood.

In conclusion, regeneration of lost or damaged adult tissues with specialized function such as muscle or neuron is possible with tissue specific stem cells viz. bone marrow/adipose tissue/cord blood. Conclusive evidence is available from well conducted clinical trials for Burger’s disease, diabetic foot ulcer, osteoarthritis and rheumatoid arthritis. Success in other degenerative diseases will soon follow.

Dr.S.G.A.Rao, Founder Chairman
Society for Regenerative Medicine &Tissue Engineering Trustee, STEM FOUNDATION

References :

1. Motukuru, Suresh K.R. et al, Therapeutic angiogenesis in Buerger’s disease, patients with critical limb Ischemia by autologus transplantation of bone marrow mononuclear cells. Journal of Vascular Surgery 48515-605-2008

2. Dr. Amarpal Suri,

3. Dr. Pradeep Kiran,

4. Dr. Rudrappa