Dr. Alka Sharma.

The potential of stem cell technology to develop therapy for many untreatable diseases through cellular replacement or tissue engineering is widely recognized. Any disease where there is tissue degeneration is the potential candidate for stem cell therapy such as burns, spinal cord injury, cardiac, Parkinson’s and Alzheimer’s, retinal, hair cell regeneration, etc. However, clinical research is based on the well established foundation of basic research. Therefore, extensive research is essential to understand the fundamental processes of cell development, relationship between stem cells and tumour formation, interaction between stem cells and microenvironment, creation of good animal models to understand disease patterns, evaluation of new drugs, etc.

This is a highly interactive field of life sciences and it requires close interaction of basic researchers, clinicians and the industry for the overall growth and development. Keeping in view its potential therapeutic applications, the need was felt to initiate programmes on stem cell science in the country. After a wide consultation with the national and international experts, priority areas in this area have been categorized into basic research, translational research, institutional development, creation of facilities/infrastructure and human resource development.

Research and Development

Basic research
In the country, both basic and clinical research are being promoted by several science agencies of the Government in various institutions and hospitals. The programmes have been identified and implemented on various aspects of both embryonic and adult stem cells such as limbal, haematopoietic, embryonic, pancreatic, neural, cardiac stem cells, generation of human embryonic stem cell lines, use of banana lectins for stem cell preservation, haematopoietic stem cells (HSC) for haplo-identical HSC transplantation, use of limbal stem cells for ocular surface disorders, isolation and characterization of mesenchymal & liver stem cells, in vitro differentiation of human embryonic stem cells to neural and non- neural lineages, etc. City cluster programmes have been implemented at Pune and Vellore by involving basic researchers and clinicians. This includes sharing of information, explore collaboration with clinicians and discuss emerging policy issues in this area, etc. In 2003, a separate Task Force on “Stem Cell Biology and Regenerative Medicine” was constituted to consider new projects, monitor the progress of ongoing projects, discuss the priority areas and others issues related to stem cells.

Major research leads

a)      Use of limbal stem cells to repair corneal surface disorders caused by limbal stem cell deficiencies. So far, more than 300 patients have been treated at LV Prasad Eye Institute (LVPEI), Hyderabad,

b)     A technology has been established at Christian Medical College (CMC), Vellore for collection, isolation and purification of HSCs for haplo-identical haematopoietic stem cell transplantation.

c)      Banana lectins have been isolated and purified showing stem cell preservation activities.

d)     Indigenous human embryonic stem cell lines are being generated at few institutions in the country.

Clinical research system established
Clinical research is an integral part of stem cell science. The ultimate outcome of the research in this field is for the welfare of the human kind. Thorough clinical research for determining the safety and efficacy of stem cells initially in animal and then in human is essential. A system to consider the clinical research proposal has been established by constituting four separate committees. They are:

(i)     “Human Studies Committee” for evaluation and guidance for clinical research particularly for development of clinical research protocols;

(ii)    “National Bioethics Committee” to ascertain rigid ethical guidelines being followed while conducting research on human beings;

(iii)  “Task Force on Stem Cells and Regenerative Medicine” to evaluate basic research and also recommend funding for clinical research based on the evaluation of the above committees and

(iv)  “Programme Advisory Committee” to consider the proposals of Centre of Excellence and infrastructure.

Clinical research
Following this system and based on the thorough review of literature, multi-centric phase-I clinical study has been implemented at five hospitals to determine the safety and efficacy of bone marrow mononuclear cells in acute myocardial infarction. The pilot study on acute stroke using bone marrow mononuclear cells has also been implemented initially at one centre and based on the results of the pilot study, the main study would be designed. The multi-centric phase-I proposal on limb ischemia is under active consideration. Efforts are being made to generate more proposals on clinical research based on the well established animal data in the field.

Stem Cell Centre and Institute
The science of stem cell is complex and extensive research is required to understand how these cells work and how the potential of these cells may be harnessed for therapeutic applications. Keeping in view major consensus, it was felt that there should be a dedicated research centre completely focused on stem cells and cell developmental science. Therefore, concerted efforts were made to establish “CMC-DBT Centre for Stem Cell Research” at CMC, Vellore to carry out basic and translational stem cell research. This centre is under construction and will be functional soon. It was further realized that only a “Centre” may not be sufficient for stem cell research in the country like India. It was felt that there is a need for a full fledged institution for stem cell research in the country. In this regard, a proposal to establish an “Institute for Stem Cells and Regenerative Medicine” is under consideration.

Facilities to handle stem cells
Though some of the institutions in the country initiated stem cell research few years ago, facilities were limited and were not adequate for taking up challenges coming continuously in this area as this is a comparatively new field of life sciences. Realizing the need to establish clean room facilities to handle stem cells and also carry out research in this field, a number of facilities have been created. These facilities have been established mainly in hospital set up because hospitals are the main source for providing these cells and no facilities were available to handle stem cells in their set up. Therefore the facilities have been created at Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh; Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow; LVPEI, Hyderabad and KEM Hospital, Mumbai.

Efforts made for Human Resource Development
Creation of human resource of desired expertise is the most critical component of stem cell research. In order to train young researchers in both embryonic as well as adult stem cells, a training proposal has been implemented jointly at NCBS and JNCASR, Bangalore. Efforts have also been made to bring clinicians and basic researchers together for close interaction by organizing a number of clinical research workshops, extensive training programmes, brainstorming sessions, etc. In addition, the training programmes have been formulated to support long and short-term overseas training in niche areas of biotechnology including stem cell research. The need was also felt for a regular discussion on the subject among the researchers in the country especially the new developments that are taking place globally in this area. In order to provide an opportunity for close interaction to the researchers, a “Stem Cell Research Forum of India” has been created. The “Forum” will provide a platform to the scientists and clinicians for close interaction for discussion and to share the achievements of their efforts. Annual conference is also being organized by this “Forum” during January 29 – February 1, 2007 in Bangalore in order to discuss various aspects of embryonic and adult stem cells with the international experts.

Draft guidelines for stem cell research
Draft guidelines for stem cell research in the country have been formulated jointly by the Department of Biotechnology under Ministry of Science and Indian Council for Medical research. Draft document was discussed jointly by both the Committees to finalize this document. The guidelines will be placed for public debate soon. As per the guidelines, stem cell research has been classified under permissible, restricted and prohibited categories. The research pertaining to adult and umbilical cord blood stem cells would be classified as permissible. It would require approval from Institutional committee. However, embryonic stem cells research falls under restricted category. It can be carried out with the approval of Institutional Committees and National Apex Committee. Research pertaining to reproductive cloning, introducing animal embryos in human, etc. has been categorized as prohibited.

Conclusion
In the country, there is an enhanced awareness among the scientists, clinicians and the industry about stem cell research. The process has gained momentum to explore the potential applications of these cells for therapeutic applications. The programme has entered into a critical phase and now faster pace of progress is envisaged.



Dr. Alka Sharma is Principal Scientific Officer, Department of Biotechnology, Ministry of Science & Technology, Government of India, New Delhi, INDIA.