All across the medical world, stem cells are igniting fresh hope and exciting new possibilities in the treatment of serious diseases. In this post, GIN’s Chief Neurosurgeon, Dr N K Venkataramana talks about different types of stem cells and their role in neuro regenerative medicine.
Stem cells are sometimes referred to as mother cells. This is because in the body or in the right laboratory conditions these cells divide and sire ‘daughter cells’. These offspring either become new stem cells (self-renewal) or specialized cells (differentiation) with more specific functions, such as blood, heart, bone or brain cells. No other cell in the body has this natural ability.
Where do stem cells come from?
Embryonic stem cells: These come from three- to five-day old embryos, known as blastocysts. These stem cells can divide into more stem cells or morph into any type of cell in the body. Such versatility means that embryonic stem cells can be used to regenerate or repair any diseased tissue and organ.
Adult stem cells: Found in small numbers in most adult tissues, such as bone marrow or fat, adult stem cells are relatively less versatile; that is, their ability to turn into various other types of body cells is limited. However, contrary to earlier belief there is now sufficient evidence to show that adult stem cells can create unrelated types of cells. For instance, bone marrow stem cells may be able to create bone or brain cells
Being a highly active functional organ the brain is prone to many diseases caused by developmental flaws, injuries, trauma, tumors, ischemic insults and a host of degenerative diseases leading to different levels of disability.
Although recent research has re-written a long-standing theory that brain cells cannot regenerate and, therefore, support a repair mechanism the fact remains that their regenerative capacity is not enough to combat diseases in many clinical situations.
This means that many crippling neurological disorders continue to remain incurable. Even as researchers deepen their understanding of the mechanics of disease in search of newer medicines, advances in the direction of enhancing the repair process have led to the use of stem cells.
Found in embryos during development, stem cells are primitive cells capable of building different human organs. Because of their ability to multiply and transform into neuronal cells they have been transplanted on adult brains afflicted by various diseases. However, research into embryonic stem cells is mired in controversy due to ethical and safety issues, the availability of embryos and the risk of transmitting infections.
Adult stem cell treatment has been used successfully for years to treat leukemia and related bone/blood cancers through bone marrow transplants. It has also been used in veterinary medicine to treat tendon and ligament injuries in horses. The use of adult stem cells for research or therapy is relatively less controversial because their production does not involve the destruction of embryos.
The discovery of stem cells in certain specified locations of an adult brain like the sub-ependymal areas has fuelled a great deal of excitement. Since bone marrow is the pipeline for a variety of blood cells, scientists looked into this area and isolated the stemcells. Over time bone marrow transplants have become an established treatment.
The isolation of bone marrow-derived mesenchymal stem cells is every exciting as they are characterized by their ability to differentiate into various connective tissue cell lineages and also produce cytokines, chemokines and many other adhesion molecules
A gamut of research in this direction has shown that these cells modulate immune cell functions. Accordingly they have been successfully used in conditions like osteogenesis imperfecta and graft-versus-host disease. Subsequent research has shown that when injected into the brain these stem cells adopt the characteristics of neural cells and have the ability to form neuronal cells, migrate to different locations, establish synaptic connections and produce neuro transmitter activity.
It has been further demonstrated that such anatomical correlations could result in functional implications leading to clinical benefits. Many clinical trials conducted to establish the safety of mesenchymal stem cells have proved that they are plura potent (capable of becoming any type of differentiated cell), genetically stable and immunologically inert, capable of multiplying rapidly. This has helped us to safely transplant these cells into brains. There is no risk of tumor formation and since it is autologus (derived from the same person) ethical issues do not arise.
With their safety established, mesenchymal stem cells are being tried as an option in the treatment of neurological diseases for which there is no viable alternative available or where patients are left with no other hope. Though the exact mechanism by which the cells act is still under debate, it appears that they reactivate existing cells, replace existing cells or rekindle the functionality of the nervous system. Also, they appear to work through many immune mediated mechanisms. We have the opportunity to create state-of-the-art infrastructure in Bangalore to harvest and culture these cells.
We have tried this method for treating spinal cord injury cases in which all other medical and surgical treatments have failed. Similarly, stem cell research is opening new windows of hope for patients of Parkinson’s and Alzheimer’s disease, stroke, multiple sclerosis and brain damage secondary to injury. There are several studies pointing to their effectiveness in cases of many severe metabolic and genetic disorders of the brain particularly among children. Long-term follow-up and a large number of trials will definitely help us to go further and validate the efficacy of stem cell-based therapies.
The process of treatment involves the aspiration of 50-70ml of bone marrow under anaesthesia. The isolated stem cells are cultured and once their sustained stable growth is confirmed a variety of immunological markers are used followed by a series of quality control processes to assure qualitative genetically stable stem cells devoid of infections.
Following this 3-4-week process, the cells are injected into the brain at a dose of 1.2 million per kg body weight. The site of injection varies from disease to disease. Stereotaxy or navigation methods are used to identify the right locations. Based on the clinical condition this can be performed either under local or general anaesthesia. Post-transplantation patients are kept in hospitals for 2-3 days for observation. In our experience except for mild fever no major side effects have been noted.
Patients are clinically evaluated once in 3 months for a full year. Though mesenchymal stem cell therapy comes with its challenges and many mechanisms still need to be understood in greater depth, the fact is that it has emerged as a breakthrough for many neurological diseases for which there was no hope in the past. We look forward to furthering this research with more and more innovations with tailor-made applications in specified disease.