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Dr Aparna Khanna Dean School of Science, NMIMS Mumbai
where damaged or diseases cells can be replaced with the cell types derived from stem cells. The first hESC line established in the world was in 1998, by Dr James Thomson and co-workers at the University of Wisconsin1. The other commonly reported sources of stem cells are bone marrow, umbilical cord blood, umbilical cord and adipose tissue/lipoaspirates. These sources are termed as “multipotent”, unlike the hESC which are termed as “pluripotent”, because of the restricted differentiation potential associated with adult stem cells. Adult stem cells are not as versatile as embryonic stem cells. More recently, another source of stem cells were discovered through a breakthrough research. These are
eases, to name a few. Fig 1 depicts a schematic representation of the use of stem cells in regenerative medicine.
Stem cell therapies: Where are we? The therapeutic potential of stem cells is immense. Two modes of stem cell transplantation exists- patient specific (autologous), and not patient specific, i.e. from one individual to another (allogenic). One of the earliest examples of stem cell transplantation has been bone marrow transplantation, following which was the cord blood stem cell transplantation. Here, the haematopoietic stem cells (HSC) from an HLA matched individual is injected intravenously, and is widely used in haematological disorders or malignancies like acute
and provided a cell therapy paradigm for neuronal repair in the human brain. This was one of the first published reports and the concept that stem cells could help in neuronal repair emerged. However, some of the limitations included; donor dependent variation, scarcity of foetal tissue, number of cells required and ethical concerns. Additionally, a fraction of patients suffered from dyskinesia (jerky movements) after transplantation, either due to the stem cells or the procedure (sterotactic surgery). Further, a recent report wherein foetal stem cells were injected into a patient’s brain, who suffered from a rare genetic disorder, ataxia telangiectasia, triggered tumours5. A word of caution is to be aware of the
Institute of Health (NIH). ClinicalTrials.gov currently lists 4196 ongoing clinical trials using stem cells, with approximately 90 per cent of the studies using adult stem cells. Similarly, in India all clinical trials being carried out using human participants have to be registered at the Clinical Registry-India, a site maintained by the Indian Council of Medical Research (ICMR). According to the registry, currently there are 29 ongoing studies registered using stem cells. The details are given in www.ctri.nic.in. Despite, the promising clinical data, a number of unanswered questions with respect to the bio-distribution of stem cells in the human body, homing or movement of the injected stem cells into
Fig 2
the induced pluripotent stem cells (iPSC)2. Here, normal skin cells can be transformed (reprogrammed) into pluripotent stem cells using genetic manipulation. This implies, that if this concept works in a clinical setting, the need for embryos would be eventually removed, and patient-specific stem cells could be made, thus enabling customised therapy. For their pioneering research on reprogramming, this year, the 2012 Noble prize in Physiology and Medicine was fittingly won by Sir John Gurdon, University of Oxford and Dr Shinya Yamanka, Kyoto University, Japan. The goal of stem cell research is to obtain functional cells which can replace damaged cells in a variety of degenerative or debilitating disorders like Parkinson’s disease, type I diabetes, spinal cord injuries, liver disJanuary 16-31, 2013
and chronic myeloid and lymphoid leukaemia, myelodysplasias, bone marrow failure syndromes, haemoglobinopathies and immune deficiencies. Since the first cord blood transplant was performed in 1988, stem cells derived from umbilical blood have been used in more than 30,000 transplants worldwide to treat a wide range of blood diseases, genetic and metabolic disorders (US Cord Blood Banking Industry Report, 2012). Cell transplantation has emerged as a potential therapy for Parkinson’s disease and has been under rigorous experimentation, both in animal models and human patients. In two well-defined double blind trials, carried out in the US, in the 1990s, the possibility of using stem cells from aborted foetuses (foetal embryonic transplantation) was investigated3,4 www.expresspharmaonline.com
adverse reaction and associated problems. Adult stem cells, the mesenchymal stem/stromal cells (MSC) are another population of stem cells found in bone marrow and in a number of other tissues, and have used for stem cell therapy. The plethora of diseases that can be cured using MSCs are graft versus host disease (GVHD), Crohn’s disease multiple sclerosis (MS), motor neuron disease (MND) and ALS, Parkinson’s disease (PD), diabetes mellitus (DM), chronic obstructive pulmonary disorder (COPD), acute myocardial Infarction (MI), dilated cardiomyopathy (DCM), osteogenesis imperfecta, osteodysplasia and liver failure to mention a few. The details of the ongoing/completed clinical trials can be obtained from www.clinicaltrial.gov, a registry of the US National
desired organs and their long term effects need to be addressed. These issues can be overcome by developing sensitive non-invasive imaging modalities, which will prove valuable in optimising cell based therapies. The treating physician should be able to address questions with respect to number of cells to be injected, viability of cells after injection and the migration pattern to the targeted organ.
Nanotechnology and biomedical applications Nanoparticles, as the word suggests, are particles with size in the “nanó” range that is 1-100 nm. The advantages of these very small sized particles are that they can traverse through blood vessels, can be administered either intravenously, oral route or inhalation. They can also be targeted to reach speEXPRESS PHARMA
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