Ministry of Science and Technology – January 2012 Update

Department of Biotechnology, Ministry of Science & Technology, Government of India, New Delhi, IndiaIndia

 

The Department of Biotechnology (DBT) was setup under the Ministry of Science and Technology in 1986 to give a new impetus to the development of the field of modern biology and biotechnology in India. In more than two decade of its existence, the Department has promoted and accelerated the pace of development of biotechnology in the country. Through several R&D projects, demonstrations and creation of infrastructural facilities a clear visible impact of this field has been seen. The Department has made significant achievements in the growth and application of biotechnology in the broad areas of medical biotechnology, agriculture, health care, animal sciences, environment, and industry.

The Department has deep involvement of the scientific community of the country through a number of technical Task Forces, Advisory Committees and individual experts in identification, formulation, implementation and monitoring of various research programmes and activities.

DBT’s Initiative on Stem Cell Research

The DBT is promoting stem cell research in the country with other Government agencies.  In India, over

40 institutions, hospitals and industries are involved in stem cell research. After a wide consultation with the national and international experts, priority areas have been identified and categorized into basic research, translational research, institutional development, human resource

development, creation of facilities and infrastructure. Several programmes have been implemented by the DBT various aspects of both embryonic and adult stem cells.

The programmes on embryonic stem cells include: generation of human embryonic stem cell (hESC) lines without mouse feeder layer, in-vitro differentiation of hESCs into neural and non-neural lineages and understanding the underlying genetic basis; genome-wide transcriptional profiling and pathway analysis in ESC and the vasculature; in-vitro targeting and functional characterization of ES cell derived dopaminergic neurons and exploration of their therapeutic potential; development of a cell therapy strategy to treat glaucoma using retinal ganglion cells generated from ES cells; in-vitro differentiation of hESCs and mesenchymal stem cells into cardiomyocytes, development of assays for toxicity testing and drug discovery using cardiomyocytes differentiated from hESCs, etc.

 

The programmes on adult stem cell research include: creation of a novel, genetically defined stem cell model of carcinogenesis; ex-vivo expansion of corneal stem cells from limbal biopsies using human amniotic membrane as a substrate and its applications in treating ocular surface disorders caused by limbal stem cell deficiencies; in-vitro differentiation of mesenchymal stem cells into cardiomyocytes; identification and characterization of lectins having haematopoietic stem cells (HSCs) preservation activity; identification of biochemical pathways involved in the HSCs regulation; characterization and differentiation of pancreatic progenitor cells/stem cells to insulin secreting cells from adult mice pancreatic tissue; isolation of multipotent adult progenitor cells from human bone marrow and their clonal expansion and differentiation into cardiomyocytes, hepatocytes and b-islet cells; stem cell therapy for stroke in rat model; analysis of the role of Notch ligands as modulators of bone marrow stem cells expansion and function; phenotypic and genotypic characterization of limbal stem cells, cultivated limbal epithelial cells and persistence of these characteristics after clinical transplantation; protein profiling of human ovarian tumor stem cells; basic biology of neural stem cells; biology of cancer stem cells; characterization of cultivated oral mucosal epithelial cells and its application for reconstructing the ocular surface in patients with severe ocular surface disease; mesenchymal stem cell therapy in induced mice skin and burn wounds; immunobiology of mesenchymal stem cells, etc.

 

Clinical research

Clinical research is an integral part of stem cell science. A system has been created to consider clinical research proposals for determining the safety and efficacy of stem cells initially in animal and then in human by constituting four separate Committees (i) “Human Studies Committee” for evaluation and guidance for clinical research particularly for development of clinical research protocols; (ii) “Ethical Committee for Stem Cell Research” 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. Following this system and based on the thorough review of literature, a multi-centric phase-I clinical study with sample size of 250 patients has been implemented at five hospitals in the country to determine the safety and efficacy of bone marrow mononuclear cells in acute myocardial infarction. Similarly, a pilot study on acute ischemic stroke was implemented initially at one center to determine the safety of bone marrow mononuclear cells. Based on the results of the pilot study, the main study with the sample size of 120 patients has been designed and implemented at five hospitals in the country. A multi-centric phase-I clinical study on limb ischemia has also implemented at few hospitals in the country.

Other DBT’s stem cell activities with the institutions and places in India

 

Stem cell Centre/Institute and Programmes

Institutes and places

CMC-DBT Centre for Stem Cell ResearchEstablishment  of cGMP facility Christian Medical College (CMC), Vellore
Institute for Stem Cell Biology and Regenerative Medicines Bangalore, Karnataka
Network programmes CMC, Vellore; Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow; Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh; All India Institute of Medical Sciences (AIIMS),  New Delhi; R&R New Delhi; National Centre for Cell Science (NCCS), Pune and National Brain Research Centre (NBRC),  Manesar
Embryonic stem cell research National Institute for Research in Reproductive Health, Mumbai; National Centre for Biological Sciences (NCBS), Bangalore; NCCS, Pune; NBRC, Manesar and Jawaharlal  Nehru  Centre  for Advanced Scientific Research (JNCASR), Bangalore; Manipal University, Bangalore and Rajiv Gandhi Centre for Biotechnology (RGCB), Kerala
Limbal stem cells LVPEI,   Hyderabad; R. P. Centre, AIIMS, New Delhi and Regional Institute of Ophthalmology, Kolkata
Neural stem cells NBRC, Manesar; National Institute of Mental Health and Neurosciences (NIMHANS),  Bangalore; NCCS,  Pune and University  of Hyderabad, Hyderabad
Mesenchymal stem cells CMC, Vellore; SGPGIMS,  Lucknow and Manipal University, Bangalore
Pancreatic progenitor cells National Institute of Nutrition (NIN), Hyderabad and NCCS, Pune
Cardiac stem cells Sree Chitra Tirunal Institute for Medical Sciences & Technology, Thiruvananthapuram and  AIIMS, New Delhi
     Cancer stem cells Indian Institute of Science, Bangalore and NCCS,  Pune
Stem cell research facilities PGIMER,  Chandigarh; SGPGIMS, Lucknow; KEM Hospital, Mumbai; LVPEI, Hyderabad; CMC, Vellore and AIIMS, New Delhi

 

Facility created for stem cell research

Clean room facilities have been created to handle stem cells at few hospitals such as Post Graduate Institute of Medical Education & Research,   Chandigarh; Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow; LVPEI, Hyderabad and KEM Hospital, Mumbai.

Training is being provided jointly by JNCSAR and NCBS, Bangalore to the students and young faculties for both embryonic and adult stem cells. Efforts have also 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. “Stem Cell Research Forum of India” has been created to provide a platform to the scientists and clinicians for close interaction and discussion on new developments and also facilitate sharing of the achievements.

Centre for stem cell research

A “CMC-DBT Centre for Stem Cell Research” has been established at Christian Medical College (CMC), Vellore to carry out basic and translational stem cell research. The center will facilitate research on basic biology of stem cells, pre-clinical and clinical research to explore full potential of human bone marrow stem cells including mesenchymal stem cells (MSCs). The infrastructure will be used to assess the role of stem cells in the area of haematology, cardiology, nephrology, neurological  and gastrointestinal  sciences.

 

Institute for Stem Cell Research and Regenerative Medicines

An “Institute for Stem Cells and Regenerative Medicines”  has been approved by the Government of India at Bangalore with CMC-DBT Centre for stem cell research as its one of the translational wings. The primary objective of the institute is to create an organizational structure that promotes growth of expertise in stem cell research, fosters interactions among basic scientists and clinicians in ways that support innovative research to address barriers to progress in the therapeutic use of human stem cells. Specific areas of research will be: basic research with interdisciplinary inputs; fundamental mechanisms of stem cell specification; stem cell niche and signaling; stem cell reprogramming; stem cell differentiation; cell cycle and quiescence in stem cells; stem cell isolation, markers, purification; stem cell genomics, epigenomics and proteomics; developmental potential of adult stem cells; isolating new human stem cell lines (ES, adult, iPS) and molecular genetic strategies. Application oriented/Translational research will include: creation of animal models of degenerative diseases and stem cell strategies; modeling of stem cell networks-systems biology approach; tissue engineering studies-scaffolds, tissue architecture, co-cultures; stem cell immunology and transplantation biology and Human physiology–stem cell perspective. The training courses will also be conducted by the institute in this area.

Salient Achievements

  • Two new hESC lines from discarded grade III blastocysts have been generated at JNCASR, Bangalore in the programmes implemented by the DBT. These cells have been characterized for pluripotency by expression of various markers and by in vitro differentiation assays. The cell lines are stable and have been cultured for many passages. These cell lines have been deposited in UK Stem Cell Bank and being used by the national and international researchers.
  • Three hESC lines have been generated on human fibroblast feeder layers at NIRRH, Mumbai. Currently these lines are being cryopreserved and assessed for genetic stability under long term culture conditions.
  • A malignant, rapidly proliferating, anchorage independent, highly tumorigenic and invasive cell-line Human Neural Glial Cell-line (HNGC-2) has been established from a glioma patient at National Centre for Cell Science (NCCS), Pune.
  • Limbal stem cells are being used to repair corneal surface disorders caused by limbal stem cell deficiencies. So far, more than 600 patients have been treated at L.V Prasad Eye Institute, Hyderabad.
  • Banana lectins have been isolated and purified showing HSCs  preservation activities by the scientists of NCCS, Pune and Indian Institute of Sciences (IISc.), Bangalore.
  • Three multi-centric clinical trials using autologous adult stem cells have been designed and implemented by the DBT on myocardial infarction, acute ischemic stroke and Critical limb ischemia.

 

Guidelines for Stem Cell Research and Stem Cell Therapy in India

 

Guidelines for stem cell research have been formulated jointly by the Department of Biotechnology, Ministry of Science & Technology and Indian Council for Medical Research (ICMR) New Delhi. The guidelines address derivation, propagation, differentiation, characterization, banking and use of human stem cells for research and therapy. The guidelines provide a mechanism to ensure that a stem cell research is conducted in a responsible and ethically sensitive manner and complies with all regulatory requirements. Summary of the guidelines for stem cell research is as follows:

Monitoring mechanism

As per this document, a separate mechanism for review and monitoring is essential for research and therapy in the field of human stem cells, one at the National level called as National Apex Committee for Stem Cell Research and Therapy (NAC-SCRT) and the other at the institutional level called Institutional Committee for Stem Cell Research and Therapy (IC-SCRT). All institutions and investigators carrying out research on human stem cells should be registered with NAC-SCRT through IC-SCRT.

 

Categorization of stem cell research

According to the source of stem cells and nature of experiments, the research on human stem cells is categorized into three areas.

1.         Permissible areas of research 

  • In-vitro studies on established cell lines from any type of stem cell viz. hES, hEG, hSS or fetal/adult stem cells may be carried out with notification to IC-SCRT, provided the cell line is registered with the IC-SCRT/NAC-SCRT and GLP is followed.
  • In-vivo studies with established cell lines from any type of stem cells viz., hES, hEG, hSS, including differentiated derivatives of these cells, on animals with prior approval of IC-SCRT, provided such animals are not allowed to breed. This includes pre-clinical evaluation of efficacy and safety of human stem cell lines.
  • In-vivo studies on experimental animals (other than primates) using fetal/adult somatic stem cells from bone marrow, peripheral blood, umbilical cord blood, skin, limbal cells, dental cells, bone cells, cartilage cells or any other organ (including placenta), with prior approval of the IC-SCRT/IEC provided appropriate consent is obtained from the donor.
  • Establishment of new hES cell lines from spare, supernumerary embryos with prior approval of the IC-SCRT/ Institutional Ethical Committee (IEC) provided appropriate consent is obtained from the donor as per guidelines. Once the cell line is established, it shall be registered with the IC-SCRT and NAC-SCRT.

2.         Restricted areas of research

  • Creation of a human zygote by IVF, SCNT or any other method with the specific aim of deriving a hES cell line for any purpose.
    • Specific justification would be required to consider the request for approval by the NAC-SCRT through IC-SCRT /IEC.
    • It would be required to establish that creation of zygote is critical and essential for the proposed research
    • Informed consent procedure for donation of ova, sperm, somatic cell or other cell types as detailed in these guidelines would need to be followed.
    • Clinical trials sponsored by multinationals involving stem cell products imported from abroad shall require prior approval of the NAC-SCRT through IC-SCRT/IEC, Drug Controller General of India (DCGI) and respective funding agency as per its procedure/Health Ministry’s Screening Committee. The process of this consideration must be completed within 3 months of the receipt of the proposal.
    • Research involving introduction of hES/hEG/hSS cells into animals including primates, at embryonic or fetal stage of development for studies on pattern of differentiation and integration of human cells into non- human animal tissues.
      • If there is a possibility that human cells could contribute in a major way to the development of brain or gonads of the recipient animal, the scientific justification for the experiments must be strong. The animals derived from these experiments shall not be allowed to breed.
      • Such proposals would need approval of the NAC-SCRT through Institutional Animal Ethics Committee (IAEC) and IC-SCRT/IEC.
    • Studies on chimeras where stem cells from two or more species are mixed and introduced into animals including primates, at any stage of development viz., embryonic, fetal or postnatal, for studies on pattern of development and differentiation.
    • Research in which the identity of the donors of blastocysts, gametes, or somatic cells from which the hES cells were derived is readily ascertainable or might become known to the investigator.

 

3.         Prohibited areas of research

  • Any research related to human germ line genetic engineering or reproductive cloning.
  • Any in-vitro culture of intact human embryo, regardless of the method of its derivation, beyond 14 days or formation of primitive streak, whichever is earlier.
  • Transfer of human blastocysts generated by SCNT or parthenogenetic or androgenetic techniques into a human or non-human uterus.
  • Any research involving implantation of human embryo into uterus after in-vitro manipulation, at any stage of development in humans or primates.
  • Animals in which any of the human stem cells have been introduced at any stage of development should not be allowed to breed.
  • Research involving directed non-autologous donation of any stem cells to a particular individual is also prohibited.

 

The details are available on the websites of Department of Biotechnology www.dbtindia.nic.in and Indian Council of Medical Research www.icmr.nic.in.

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