In september 2006 India’s first stem cell transplant center was opened in Chennai, Tamil Nadu, by a private company called LifeCell, in collaboration with United States-based Cryo-Cell Inc. This center marks another milestone in Indian efforts to stay on top of this burgeoning medical trend without getting entangled in ethical controversies.
The medical and economic potential of stem cell research has long been recognized, and measures are slowly being put in place to establish India as a reliable supplier of stem cell-related resources. Guidelines regulating stem cell therapy and research have been set in place, and efforts have begun toward establishing a national network of stem cell researchers and research centers.
Indian research in stem cells includes work in both embryonic and adult stem cells and basic science, as well as clinical research. This differs from policies in some other countries that permit the use of only adult stem cells. In addition, it is legal for human stem cells to be obtained from aborted fetuses and in vitro fertilization clinics, as well as from adult tissues, after obtaining informed consent and institutional review board approval. However, the creation of embryos for the sole purpose of harvesting stem cells is forbidden.
Work with stem cells has been continuing for over 20 years in certain medical centers in the country, including cord blood and bone marrow-derived hematopoietic stem cells in hospitals in New Delhi, Mumbai, and Vellore. Worldwide, old techniques have been refined and new ones developed, and new uses have been discovered for these cells. This advent of new technology and ideas has had an effect on Indian stem cell research as well. Projects involving the use of limbal, hematopoietic, embryonic, neural, islet, liver, and bone marrow-derived stem cells and involving preservative agents for stem cells have been awarded grants by various government agencies over the past few years.
The principal funding agencies have been the Indian Council of Medical Research and the Department of Biotechnology of India’s Ministry of Science and Technology. These agencies have also been instrumental in the establishment of guidelines and regulations for the use of stem cells in practice and research and in charting the course of future stem cell research in the country.
NATIONAL INITIATIVE
One of the main difficulties faced by stem cell researchers in India has been the lack of resources for large-scale studies, as most research groups were fragmented. Plans for a nationwide stem cell research initiative were put forward in 2005 by the Department of Biotechnology. One of the initiative’s primary aims is to bring together privately and publicly funded stem cell research groups in and around a city to form stem cell city clusters. These clusters were envisioned with the expectation that they would permit a pooling of resources from both privately and publicly funded stem cell research institutes, as well as encourage interactions between basic science researchers and clinicians.
Another effort toward promoting stem cell research in India involves the establishment of specialized centers for research and therapy using stem cells. The chief objective of these centers is to promote multidisciplinary research to address clinical issues. In 2005 the Department of Biotechnology announced that it would support medical schools or institutions interested in establishing specialized centers for cell-based therapy. These centers will be provided a grant for a maximum of 10 years—an initial period of five years that can later be renewed for a further five.
During the first two years, the centers are expected to concentrate on preclinical research such as standardization of laboratory methods, the formulation of standard operating procedures, safety monitoring, data monitoring, and so on. They are also expected to conduct preclinical studies to help obtain clearance from the Drug Controller General of India (DCGI; the body that regulates the testing and marketing of new drugs or procedures in India) for future clinical trials. By the third year, all preclinical studies should be completed and clinical studies started.
The formulation of standard operating procedures, evaluation of study proposals for research projects, and evaluation of data are to be carried out by a Task Force for Stem Cell Research and the subcommittees constituted by it. Because the driving force of this program is benefit to the patient, all applicants for the grant are required to conduct research that can provide a translation of basic science research to clinically applicable studies. They must provide detailed descriptions of safety monitoring and data monitoring programs along with their research proposals. These centers are also required to organize annual meetings between the investigators involved to facilitate a regular exchange of information.
ETHICAL CONTROVERSIES
Certain controversies in the past raised the issue of a lack of ethical oversight. In one instance, Indian researchers in the Institute of Immunohematology, a center of the Indian Council of Medical Research (ICMR), were accused by other researchers in the country of violating India’s policy of rejecting the conduct of clinical trials of unproven procedures or treatments developed outside India when they are conducted exclusively on Indian patients.
In another instance, a Delhi-based fertility specialist created a furor when she claimed to have used embryonic stem cells for the treatment of different diseases and injuries in around 100 patients. Although several of her patients claimed that her therapy had caused dramatic improvements, the lack of any preliminary studies (to determine possible adverse effects or to prove efficacy) and of a standard operating procedure ignited several protests against what was viewed as indiscriminate use of an as yet inadequately researched technique. Other researchers feared that the legislato-rial backlash would be so severe as to cripple stem cell research in the country.
Unlike in the United States, embryonic stem cell research is legal in India. There are no or few public debates about abortion, which is also legal across the country, raising the issue of India being a source of stem cells. In an effort to avoid exploitation and unethical behavior, the country is tightening regulations on embryonic stem cell research. Until the advent of these enforceable rules (based on the Indian Council of Medical Research’s guidelines), stem cell research in India was a rapidly burgeoning but uncontrollable trend. With these rules, it is envisaged that research may be more effectively regulated.
GUIDELINES
The ICMR published, in 2006, the National Guidelines for Stem Cell Research and Therapy. These guidelines deal with the following topics: the mechanisms for review and monitoring; classifications and definitions of stem cell lines; classification of areas of stem cell research into permissible, restricted, and prohibited; clinical uses of umbilical cord blood and research using fetal cells or placenta; derivation of human embryonic stem cell lines, the procurement of materials for their generation, and their banking and distribution; the responsibility and accountability of the researcher; the use of stem cells for therapeutic purposes; rules governing international collaboration; and the commercialization of stem cell research and patent issues arising from it.
These guidelines also express the need for two regulatory committees for stem cell research: a National Apex Committee for Stem Cell Research and Therapy (NAC-SCRT) and an Institution Committee for Stem Cell Research and Therapy (IC-SCRT). These committees require that the autonomy of donors of material for research purposes be preserved by such methods as a prohibition of financial or other enticements for the donation of human oocytes, sperm or embryos, or human somatic cells.
In the case of women seeking infertility treatment, the attending physician and the investigator intending to use the human embryonic stem cells should not be the same person, to avoid coercion; the consent of donors of supernumerary embryos should be procured at least 24 hours in advance and not at the time of donation; and the donors should be informed of their right to withdraw consent up until the time the blastocyst is actually used in the derivation of cell lines. The guidelines also stipulate that any profit made from the commercialization of intellectual property rights be shared with the community that contributed, directly or indirectly, to it.
RESTRICTIONS
ICMR’s National Guidelines for Stem Cell Research and Therapy categorize stem cell research and therapeutic procedures into three categories: permissible, restricted, and prohibited. The permissible areas of research and therapy, all carried out with the prior approval of the IC-SCRT or the DCGI, include in-vitro and in-vivo studies on established cell lines from any type of stem cell; in-vivo studies on any non-primate experimental animals using fetal/adult somatic stem cells from any organ provided appropriate consent is obtained from the donor; establishment of new human embryonic stem cell lines from spare embryos after obtaining prior donor consent; establishment of umbilical cord stem cell banks; processing of cells for clinical trials.
The restricted areas of research include creation of a human zygote with the specific aim of deriving a human embryonic stem cell line for any purpose; clinical trials sponsored by multinationals involving stem cell products imported from abroad (they will require prior approval of the NAC-SCRT); research involving the introduction of human embryonic stem cells, human embryonic germ cells or human somatic cells into animals at an embryonic or fetal stage of development; studies on chimeras; research in which the identity of the donors of the cells from which the human embryonic stem cells were derived may become known to the investigator.
The prohibited areas of research include any research related to human germ line genetic engineering or reproductive cloning; any in-vitro culture of an intact human embryo beyond fourteen days; transfer of human blastocysts generated in the laboratory into a human or non-human uterus; any research involving implantation in-utero of a human embryo after in-vitro manipulation.
The guidelines also prohibit breeding of animals into which human stem cells have been introduced and the nonautologous donation of stem cells.
