Considering the health needs of the country marked by sharp growth of non-communicable diseases such as diabetes, cardiovascular diseases and cancer, the still emerging field of regenerative medicines in general and stem cell research in particular have high potential and India is holding an advantage in many ways. But, that apart, stem cell research in the country is in a decisive stage, needing a right direction.
Stem cell research, although in its infancy, has emerged as a cutting edge science discipline hoping to make medical breakthroughs for meeting health needs. It has been identified as one of the promising areas of biotechnology for “regenerative medicine” in providing tools to repair or replace tissues or cells damaged by injuries or diseases, like heart diseases, stroke, spinal injuries, diabetes mellitus, retinal degeneration and muscular dystrophy and Parkinson’s, Alzheimer’s diseases. And it is taking deeper roots in the country, becoming an important tool for basic and applied science.
Globally, the regenerative medicine and stem cell technologies are estimated to become a US$ 500 billion market over the next 20 years. To establish India in an advantageous position in the fast developing global stem cell market, we need to have a strategy in place. It takes 10–12 years for a new drug discovery, whereas it takes just three to five years in stem cell research. The pre-launch cost of development for a new drug is US$ 500 million against the US $200 million in stem cell research. And the success rate of a new drug is 5–10 per cent against 50 per cent or better in stem cell research, according to different studies. Stem cell technology can reduce pharmaceutical R&D by 25 per cent each year, with savings of up to US $25 million in each drug market.
India's potential
Dhritarashtra, the Kaurava king, and his wife Gandhari in the Indian mythology might be credited for conducting the first cloning in the world, if stories are to be believed. According to one version about their 100 sons, Gandhari was unable to have any children for a long time, though Vyasa granted her the boon to have 100 sons. She eventually became pregnant, but did not deliver for two years, after which she gave birth to a lump of flesh. Vyasa cut this lump into a hundred and one pieces, and these eventually developed into a hundred boys and one girl.
Even if we don't heed to the mythological theories that can prove India to be a fertile land for stem cell research, some analysts believe that stem cell research has a rich relation to the Indian traditional medicine system of Ayurveda. Stem cell principles can go with basic ayurvedic principles of purging and rejuvenating the body through therapies.
So, mythologicaly, historically and now technically, India is placed as one of the best bets for taking the advancements of stem cell research and therapy further.
Current status
Recently, Chennai - based Lifecell International was in the news for its efforts to cure thalassemia of a girl through cord blood stem cells. In March 2009, the stem cells transplantation was done at the Apollo Hospital and it helped the eight-year-old Thamirabharuni get rid of Thalassemia. The stem cells that were transplanted came from her brother Pugazhendhi’s cord blood and his bone marrow.
But there was also another news. The AIIMS, which has been doing some commendable job on the stem cell research front, had to drop two ongoing trials because of poor response from the patients. The trials were being carried out on those suffering from muscular dystrophy and Motor Neuron Disease (MND). The advanced research has also failed to work on patients with cardio-vascular diseases or those who suffered strokes. Initial results had indicated the doctors were on the right track, but that was it. Apart from the two trials, doctors are at present working on stem cell research in strokes, cerebral palsy, injuries of the spinal cord and Parkinson’s disease. Most trials are assisted by the Department of Science and Technology. Both these instances sum up the current story of stem cell research in the country, giving lots of points for pondering.
There are more than 35 research institutes, hospitals, and firms involved in stem cell research. These sites include large public hospitals such as the AIIMS, dedicated private companies such as LifeCell in Chennai, and research institutes such as the National Centre for Cell Sciences (NCCS) in Pune. Their activities are varied and include basic research, clinical trials, treatments, and service provision.
Some institutes focus primarily on basic research. Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Bangalore studies ESC differentiation into cardiovascular cells. Other institutes balance basic research with applied activities such as animal modelling, clinical trials or pilot treatments. NCCS has conducted animal and preclinical analyses of bone marrow stem cell injections for pancreatic regeneration. Research efforts from this institute succeeded in rescuing mice with experimentally induced diabetes after a 30 day follow up sometime back. The scientists at NCCS hope to extend this work to an autologous clinical trial in human diabetic patients. The institute is working to establish a team of clinicians, scientists, and patients to act as a platform for the trial, a process they estimate will take 3–4 years. Others, such as the Central Leather Research Institute (CLRI), hope to transfer their current stem cell research to the private sector.
Christian Medical College and Hospital (CMC) in Vellore has a centre for stem cell research in collaboration with DBT to promote translational research with stem cells. Sankara Nethralaya has also built a research building in which stem cell research is a key area, with projects covering diverse areas such as corneal stem cells, cancer stem cells, and the use of stem cells in tissue engineering.
Stempeutics, in Bangalore, is the research arm of Manipal Education and Medical Group (MEMG). Its efforts are designed to divide resources between basic and clinical research. Areas of basic research include mesenchymal stem cells, cancer biology and cardiovascular research, while clinical trials are underway for myocardial infarction, critical limb ischemia, cerebral stroke and multiple sclerosis.
Most Indian companies in the field of stem cells are primarily involved in umbilical cord blood banking, an established practice that provides the industry with a commercial base. Some of these companies are beginning to develop stem cell-based treatments as well, often linked to Indian health needs. The Indian firms LifeCell (in Chennai), CryoStemCell (in Bangalore), and Reliance Life Sciences (in Mumbai) have all established umbilical cord blood banking facilities. Many of these firms also have international links. Some Indian companies have also begun to develop treatments for various diseases.
At Reliance Life Sciences, the embryonic stem cell group is engaged in developing cell-based therapies to address neural, cardiac and metabolic disorders. Further, they are trying to delineate the intricate signal transduction mechanisms governing stem cell differentiation by proteomic studies. The group has also focused on identifying candidate biomarkers to predict or measure pharmacological efficacy and toxic response by employing the hES cell metabolome.
Regulatory front
Notwithstanding all negative factors, India is still one of the few countries to have a clear set of guidelines. Indian Council of Medical Research and Department of Biotechnology jointly have formulated guidelines for stem cell research and therapy in the year 2007. The guideline document covers the requirements for banking and registry of human embryonic stem cell lines only. In view of the recent field developments and public opinion on emerging issues in the area of stem cell research, these guidelines are being debated in four regions of the country, according to official sources.
The Centre has recently constituted the much awaited National Apex Committee for Stem Cell Research and Therapy (NAC-SCRT) for effectively reviewing and monitoring the stem cell research in the country. Dr Mammen Chandy of Christian Medical College (CMC), Vellore will be the chairman of the committee. The NAC will set up standards for safety and quality, quality control, procedures for collection and its schedule, processing or preparation, expansion, differentiation, preservation for storage, removal from storage to assure quality and/or sterility of human tissue, prevention of infectious contamination or cross contamination during processing, carcinogenicity and xenotransplantation.
A few issues
Along with all the positive strides made so far, Indian scenario also is vibrant with the challenges ahead, especially as the sector has reached a critical stage of growth. No separate regulatory framework for stem cell banking has been established. Till date stem cell banking is only referred to as cord blood banking. The cord blood or cord blood stem cell banking is considered under the same regulatory requirements as for blood banking for which license from Drug Controller General of India is required.
There are also concerns about the private stem cell banks for yet-to-be-developed therapies. Even if therapies are developed, stem cells derived with today’s methods and medical approaches may be inappropriate for future applications, according to experts. As a translational research field, stem cell development requires a high degree of linkage between basic and clinical expertise. And that is another grey area.
India’s guidelines are relatively permissive when compared to other countries, some feel. Regarding hESC research, one study surveyed 50 countries and found that hESC research was allowed under strict conditions in 23 countries and banned in five, while the rest had no explicit policy. The Indian guidelines are not legally binding. Going by the track record, imposing guidelines is not easy task in the country.
With hospitals and clinics already initiating stem cell-based trials and experimental procedures, the Indian government needs to proactively enforce its new guidelines. If it fails to do so, a poor stem cell regulatory framework may become a significant hindrance to the field’s development, particularly as related to international collaborations and commercial links.
It is time for framing a national agenda and clear cut policy that can help in therapeutics. India is capable of leading from the front given its early success, potential and the proactive, favourable regulations of government agencies.