cell biology, human embryonic stem cells, human therapeutics, regenerative medicine, stem cell alternatives, stem cell therapeutics
A Garg. Stem Cell Therapeutics: Exploring Newer Alternatives to Human Embryonic Stem Cells. The Internet Journal of Health. 2007 Volume 8 Number 1.
Stem cells therapeutics has come a long way since stem cells and their potential was discovered for the first time. Intense research into cellular biology of stem cells has revealed that they possess immense potential for curing many human diseases. Research done in last couple of decades revealed that a particular class of stem cells called, “Human embryonic stem cells (HESCs)” possessed exceptional self-renewal and pluripotency properties. There ability to differentiate into specialized cell lineages of all three embryonic germ layers contributed further towards their popularity. However, in recent times HESCs have come under the cross-hairs of critics, politicians and religious groups due to certain technical and ethical concerns related to them. Such problems with HESCs-research have forced stem cell researchers to start exploring the prospects of using alternatives to HESCs for regenerative medicine and therapeutics. In the present review, various sources of stem cells have been described, which in near future, have the potential to replace HESCs in regenerative medicine.
Stem cells have emerged as a revolution in the field of regenerative medicine. In last couple of decades, intense stem cell research has given us important insights into nature of these cells and their potential for organ formation as well as regeneration and repair after injuries (National-Academy-of-Sciences, 2002). Tissue repair systems in mammals are mostly based upon dedifferentiation-independent processes regulated and governed through pre-existing stem cells or progenitor cells, which is the reason why stem cells have been at the heart of regenerative medicine. Regenerative medicine deals with all the tissues in human body, which was the reason why stem cells having the capability of differentiating into any type of human tissue cell with considerable capacity were required. Human embryonic stem cells (HESCs) were found to live up to this requirement, since they exhibited the properties of indefinite self-renewal and pluripotency (National-Academy-of-Sciences, 2002). Over a period of time, it has been proved that HESCs can differentiate into specialized cell lineages of all three embryonic germ layers in relatively simplified cultures, thereby contributing further towards their popularity. However, even though HESCs hold tremendous promise there are certain major ‘technical' obstacles in the successful and safe clinical application of these cells (National-Academy-of-Sciences, 2002). Firstly, the cell differentiation factors responsible for tissue-specific differentiation of HESCs are not fully characterized. Secondly, there is a good possibility of HESCs derived cells facing immune rejection from the recipient's body. Moreover there is also a risk of these cells driving the production of teratoma or teratocarcinomas. Lastly, the use of HESCs has received severe ethical criticism since cultivation of HESCs involves destruction of an embryo, which is religiously considered to be a potential human-being (Reichhardt
Pluripotent Aminotic Epithelium Cells (AECs)
Pluripotent amniotic epithelium cells are kind of stem cells derived from the amniotic membrane. Such stem cell-like cells, have found important application in tissue repair as these cells lack HLA-molecules on their surface, thereby making them non-immunogenic and ideal for regenerative purpose (Strom and Miki, 2003). In fact, amniotic membrane material has found good application in treatment of human corneal injuries (Shimmura and Tsubota, 2002). These amniotic membrane cells have also been reported to exhibit neural characteristics e.g. expression of nestin, BDNF and dopamine (Kakishita
Trophoblast-derived Stem Cells (TSC)
Trophoblast's portion that is in contact with inner-cell mass (ICM) of the blastocyst has been found to form extraembryonic ectoderm (ExE) and ectoplacental cone (EPC). Research has found existence of certain stem cells termed as Trophoblast-derived Stem Cell (TSCs) in the ExE (Tanaka
Endometrial Regenerative Cells (ERC)
Endometrial Regenerative Stem Cells (ERCs) are small population of stem-cell-like cells in the menstrual blood, which have been hypothesized to play role in angiogenesis phase of the menstrual cycle in the endometrium (Bulletin-Board, 2008). Research on the differentiation potential of these cells has shown that they are capable of differentiating into endodermal (pancreatic, hepatic, respiratory epithelium), mesodermal (osteocyte, endothelium, adipocyte, myocyte, cardiomyocyte) as well as ectodermal (neuronal) lineages (Meng
Placental-derived Stem Cells (PDSC)
Placenta has been reported to contain an important population of multipotent stem cells called Placental-derived Stem Cells (PDSCs), exhibiting characteristics of HESCs including expression of markers like OCT-4, SOX-2, SSEA1 as well as c-Kit (Matikainen and Laine, 2005). These cells have been shown to resemble mesenchymal stem cells and differentiate into various lineages like hepatocyte, vascular-endothelial, pancreatic and neuronal (Strom and Miki, 2003). PDSCs have also been isolated from amniotic membrane. PDSCs seem to be promising for regenerative medicine as they are easy to obtain as well as store yet PDSCs haven't been yet tested in published clinical studies. Moreover, their actual number in a single placenta hasn't been confirmed. To make matters worse, PDSCs have been found to possess unusual property of invasiveness (naturally required during embryo-implantation in placenta), which could increase the threat of teratomas during clinical therapeutic usage. Thus, there is need for extensive research so as to harness the potential of these stem cells.
Umbilical Cord Blood Stem Cells (UCB-SC)
Umbilical Cord Blood (UCB) has been recognized as a prime source of haematopoietic stem cells for a long time (Matikainen and Laine, 2005). Biggest advantage of UCB is that, it can be easily collected from the umbilical vein of the placenta which would be otherwise discarded after the birth. UCB has been routinely used in treatment of haematopoietic malignancies as an alternative for bone-marrow transplantation (Grewal
Amniotic Fluid Stem Cells (AFSCs)
Amniotic Fluid Stem Cells (AFSC), as the name suggests are novel cells derived from the amniotic fluid. Research has revealed that AFSCs could differentiate into at least 6 cellular lineages representing all three germ layers (De Coppi
Adult Stem Cells (ASCs)
Adult Stem Cells (ASCs) are tissue-resident cells found in all mammalian organisms. ASCs carry out a critical function of maintaining homeostasis in many human-tissues by assisting in wear and tear of the body and constantly acting as source of newer mature cells, which take place of old cells. ASCs have been at the top of the list as alternatives for HESCs in the field of regenerative medicine (Mimeault
ASCs are definitely less controversial than HESCs. Moreover, there have been 1,373 publicly available human clinical trials related to ASCs (As of April 2, 2007) while there have been no such trials for HESCs (Domestic-Policy-Council, 2007, Apr 2), which further adds upto the importance of ASCs. However only disadvantage of ASCs is that they are scarce and hence hard to isolate and culture. This actually increases the overall cost and time for the treatment. In next couple of decades, it's expected that the regenerative-therapy based on ASCs would improve several folds.
Induced Pluripotent Stem Cells (iPS)
Induced Pluripotent Stem Cells (iPS) are by far the most exciting alternatives proposed for HESCs in the field of regenerative medicine (Cibelli, 2007). The initiative for the production of these cells was taken solely with the purpose of circumventing the ethical issues associated with the HESCs (Takahashi
Human Embryonic Stem Cells have enormous potential yet the research relating to them has been crippled largely due to the ethical debate against them. These ethical concerns have been the reason behind recent initiative to find alternatives for HESCs in regenerative medicine. Of all the alternatives proposed for HESCs most impressive ones have been, induced Pluripotent Stem-Cells, Amniotic Fluid Stem-Cells, Umbilical Cord Blood Stem-Cells and Adult Stem Cells. For a particular alternative to replace HESCs in regenerative medicine, it ought to have almost all properties of HESCs along with other properties like non-immunogenic and non-teratomic nature. These cells have tremendous potential as well as power and they need to be handled carefully. Present trends have proved to be encouraging and it's expected that in coming years there would be more such breakthroughs, which would allow researchers to replace HESCs with other alternative stem cells. Such breakthroughs may revolutionarize the field of regenerative medicine and provide relief to millions of patients who are currently in need of stem cell based treatments.
Abhishek D. Garg MSc Biosci. Hum. Genet. (Leeds) Post-graduate Student and Commonwealth Scholar 2007-08” under Faculty of Biological Sciences, University of Leeds, UK. Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT (Yorkshire) United Kingdom. e-mail – firstname.lastname@example.org