INTRODUCTION

Stem cells are the remarkable cells that have the unique potential to develop into many different cell types dur- ing embryonic and adult life, where they divide and replenish until the animal lives. Additionally stem cells play a signi"cant role in repair, by continuously divid- ing and replacing old cells as long as the animal remains viable. When a stem cell divides, each new cell has the potential either to remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell. Stem cells are also called as the “Pluripotent cells” or “Master cells” owing to their unique ability to make cells from all the three basic body layers, so they can potentially produce

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*Corresponding Author: Received 30th October, 2015

Accepted after revision 10th December, 2015 BBRC Print ISSN: 0974-6455

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any cells or tissue the body needs to repair. This property is known as “pluripotency”. Ever since their discovery in 1960, stem cells have furnished the myriad of pos- sibilities for treatment, regeneration, and indeed, served as the key to solve the mystery of life, (Schugar et al., 2008 ,Grskovic et al., 2011, Carpino et al., 2012 Ebert et al. 2015).

Stem cells are unique and can be distinguished from other cell types by two important characteristics. Firstly, they are unspecialized cells capable of renewing them- selves through cell division, sometimes after long periods of inactivity. Secondly, they can be induced to become tissue- or organ-speci"c cells with special functions under certain physiologic or experimental conditions. In some organs, such as the gut and bone marrow, stem cells

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regularly divide to repair and replace damaged tissues. In other organs, however, such as the pancreas and the heart, stem cells only divide under special conditions.

Stem cells were earlier classi"ed into two major cat- egories: Embryonic and Non- Embryonic “somatic” or “adult” stem cells. Embyonic cells were derived from mouse embryos and were studied in quite detail. Later human embryonic stem cells were derived from human embryos and were grown in laboratory. These cells are called human embryonic stem cells. In young embryos (3- to 5-days) called a blastocyst, the inner cells give rise to the entire body of the organism, including all of the many specialized cell types and organs such as the heart,

lungs, skin, sperm, eggs and other tissues (Eckman, 2014 and Ebert et al., 2015).

In some adult tissues, such as bone marrow, muscle, and brain, discrete populations of adult stem cells gener- ate replacements for cells that are lost through normal wear, injury, or disease. Adult stem cells typically gener- ate the cell types of the tissue in which they reside. For example, a blood-forming adult stem cell in the bone marrow normally gives rise to the many types of blood cells. It is generally accepted that a blood-forming cell in the bone marrow—which is called a hematopoietic stem cell—cannot give rise to the cells of a very different tissue, such as nerve cells in the brain.

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Recently, revolutionary advancement in stem cell research has reached a whole new level where scientist have created specialized adult cells that can be “repro- grammed” genetically to assume a stem cell-like state. This new type of stem cell, are called “induced pluripotent stem cells (iPSCs)”. Induced pluripotent stem cells (iPSCs) were "rst described in 2006 and have since emerged as a promising cell source for clinical applications. They were "rst developed in 2006 in mice by the Japanese scien- tist Shinya Yamanaka, followed by the demonstration of this technique in human cells, (Yamanaka and Takashi 2006 and Yamanaka 2012). Enormous efforts have been made to apply iPSC-based technology in the clinic, for drug screening approaches and cell replacement therapy. Moreover, disease modeling using patient-speci"c iPSCs continues to progress for possible treatment of rare dis- orders, (Sebastian et al., 2014).

Both human embryonic stem (hES) cells and induced pluripotent stem (iPS) cells are pluripotent: they can become any type of cell in the body. While hES cells are isolated from an embryo, iPS cells can be made from adult cells. In a nutshell stem cells are roughly catego- rized as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs). ESCs are derived from the inner cell mass of pre-implan-

tation embryos and demonstrate excellent pluripotency, but their use is confounded by ethical issues regarding the destruction of the blastocyst (Murray and Keller, 2008).

MSCs are obtained from adult adipose tissue, blood, bone marrow, and cord blood and are thus free from ethical concerns, but their use is still limited by low cell numbers and diminished pluripotency. However, the more recently introduced iPSCs show enormous promise for disease mod- eling and regenerative medicine because their pluripotency is similar to that of ESCs, while their utilization is without ethical controversy (Zaehres and Scholer, 2008).

THE STEM CELL POTENTIAL

As researchers continue to unfold the enormous poten- tial of stem cells, their use in cell based therapies to solve many boggling mysteries of disorders have begun to emerge. But can stem cells mend a broken heart, treat a gene defect or cure blindness? It is quite a fact that cardiovascular diseases have been one of the most detri- mental diseases, and a major area of concern accounting for the number one cause of deaths around the world. Nearly 2,600 Americans die of cardio vascular disease each day which is approximately one person every 34 seconds. An abnormal heart condition results due to

oxygen deprivation, thereby resulting into killing cardi- omyocytes that gives rise to a number of events leading to heart failure. Therefore restoring or regeneration of damaged heart tissues can serve as a promising method to rectify this condition.

Interestingly, stem cell therapy has furnished great hopes in treatment to numerous cardiac conditions. Embryonic and adult stem cells that are naturally present in heart, muscle, mesenchymal, endothelial, and umbili- cal cord cells have been investigated thoroughly as pos- sible sources for regenerating damaged heart tissues. All have been explored in mouse or rat models, and some have been tested in larger animal models, such as pigs.

Importantly, stem cells are already present in clinics especially HSCs (haematopoietic stem cells), which have been successfully used for more than 40 years in bone marrow transplantations to treat diverse blood disor- ders such as leukaemia (Burt et al., 2008) . Future clini- cal applications of stem cellsare focusing on a number of degenerative diseases (i.e. disease in which one cell type or part of an organ fails) which could potentially be treated using stem-cell-based therapy. This includes major metabolic diseases such as T1D (Type 1 diabetes), caused by the destruction of insulin-secreting -cells (Baetge, 2008), diverse brain and myelin disorders in which speci"c neural cells are targeted such as MS (mul- tiple sclerosis), PD (Parkinson’s disease) or HD (Hunting-

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ton’s disease), heart disease, where some cardiac cells need to be replaced upon myocardial infarction, and genetic diseases like myopathy, where a speci"c subtype of cells are not functional.

Recently, an area that has sparked great interest is the discovery of stem cells in the “biliary tree” – a network of drainage ducts that connect the liver and pancreas to the intestine. Stem cells hold tremendous potential as a source of insulin-producing cells, thereby posing hope to treat diabetes and possibly help save millions of lives (Carpino et al., 2012). Ongoing studies are aimed at establishing that these cells can be used to reverse diabetes in pre-clinical models.

Stem cells can be used to treat patients who have dam- aged corneas and are either blind or going blind. Stem cells that occur naturally in the eye are being extracted and grown in laboratory forming sheets of cells that are late implanted into the eye. The presence of stem cells on the cornea triggers the eye to repair itself resulting in restoration of eyesight in many patients (Morgan, 2012).

Furthermore, laboratory studies of stem cells have enabled scientists to learn about the cells’ essential properties and what makes them different from special- ized cell types. Scientists are already using stem cells in the laboratory to screen new drugs and to develop model systems to study normal growth and identify the causes of birth.

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THE STEM CELL CONTROVERSY!

Stem cell research faced a lot of heat and excitement when back in 1998; stem cells were "rst harvested from human embryos. Until recently, the only way to get pluripotent stem cells for research was to remove the inner cell mass of an embryo and put it in a dish. The idea of destroying a human embryo can be disturbing, even if it is only "ve days old.

Stem cell research thus raised dif"cult questions:

•Does life begins in mother’s womb or at the time of birth?

•Is a human embryo comparable to a human child? As the debaters often question, the destruction of human embryo to be an abortion, as it is unethi- cal to destroy the embryo which has a potential to develop into a human being.

•Does a human embryo have any rights or moral status at all?

•Might the destruction of a single embryo be justi- "ed if it provides a cure for a countless number of patients? Many supporters believe that the costs of diseases both in monetary and suffering are insuf- "cient to permit discontinuation of this promising therapy.

•Besides the ethical issues there have been certain limitations that result in causing traction in the easy usage of stem cell therapies. The multistep process that the scientists have developed using pluripotent stem cells is highly speci"c and holds great potential. However these highly specialized cells are not ideal for direct treatment as they require careful instruction to become speci"c cells and may result into causing tumors if injected into the patients.

IS THE DEBATE OVER?

Stem cell research has indeed answered many questions that were once beyond our intellect. However, there is still much to learn about how stem cells work in the body and their capacity for healing. Safe and effective treatments for most diseases, conditions and injuries are the future target of research. One of the crucial ele- ments in assessing stem cell safety is the question: once implanted into the patient do the cells act as they are intended? It is predicted that stem cells may begin to divide uncontrollably and differentiate into cancer cells, leading to tumor growth.

Addressing the ethical issues concerning the use of human embryos, the technique of creating induced pluripotent cells have somewhat calmed down the dis- cord. iPS cells provide a relatively easy and inexpen-

sive method for creation of ES-type cells directly from virtually any tissue source or individual. The original technique to reprogram a normal to become an iPS cell involves adding four genes directly to a human cell such as a skin "broblast cell, with the genes added using a viral vector. The iPS cells behave like ES cells, but the technique does not use embryos, eggs, or cloning, mak- ing it an ethical way to produce “pluripotent” stem cells (cells that potentially might form any body tissue). In contrast, the usual way to produce ES cells is by taking an embryo (produced by the normal process of fertiliza- tion, or by cloning, i.e. “somatic cell nuclear transfer”) and destroying the embryo to extract the ES cells.

With these breakthroughs stem cell research has been a focus for hope and promise. The cure for defected tis- sues and organs by one’s own cells, without the need for a matched donor was once risky owing to foreign cell rejection. Cell –based therapies have opened up fascinat- ing routes for treatment of diseases that were untreat- able. In addition embryonic stem cell research may lead to fast, reliable methods of screening novel drugs for ef"cacy and toxicity without performing these tests on humans. There is no doubt that stem cells have great potential for treating diseases but unfortunately there are doubts that still exists that accompany both ethi- cal and moral rami"cations of pursuing this potential. Embryonic stem cell research is one such operation that forces scientists, policy makers, and the larger society to construe what forms a human life and to ponder: Is it morally acceptable to violate the rights of a human life for the sake of medical progress? (Eckman, 2011).

Besides the political argument there exists a lot of sci- enti"c apprehension. Will stem cells help us unravel the path of cellular development and differentiation? Could we develop stem cells for transplants that will not trig- ger autoimmune response within new host? Some day in the future, could scientists use stem cells to eliminate the need for human subjects in drug tests? Despite the doubts and dilemma stem cell research has been a gleam of hope for treating medical conditions like Alzheimer’s disease, Parkinson’s disease, spinal cord injuries, birth defects, heart diseases, diabetes and many more. It may also help reduce risk of transplantation and provide bet- ter knowledge to replace damaged organs. These bene"- cial stem cell properties will almost assuredly encourage further research and applications for a future.

REFERENCES

Adrian K. K. Teo, Ludovic Vallier (2010). Emerging use of stem cells in regenerative medicine Biochemical Journal,428(1), 11-23.

Baetge E.E. (2008) Production of -cells from human embry- onic stem cells. Diabetes Obes. Metab.10(Suppl. 4):186–194.

Burt RK., Loh Y., Pearce W., Beohar N., Barr WG.(2008). Clinical applications of blood-derived and marrow-derived stem cells for nonmalignant diseases. JAMA, J. Am. Med. Assoc. 299:925–936.

Carpino G, Vincenzo Cardinale V, Onori P (2012) Biliary tree stem/progenitor cells in glands of extrahepatic and intraheptic bile ducts: an anatomical in situ study yielding evidence of maturational lineages. J Anat., 220(2): 186–199.

Eckman J (2011). Human Embryonic Stem Cell Research. Issues in Perspective. 2011. Web. 14 Apr.

Ebert AD, Sebastian Diecke, Ian Y Chen and Joseph C Wu (2015) Reprogramming and transdifferentiation for cardiovas- cular development and regenerative medicine: Where do we stand? EMBO Mol Med. 2015 Sep; 7(9): 1090–1103.

Grskovic M, Javaherian A, Strulovici B, Daley GQ (2011). Induced pluripotent stem cells: opportunities for disease mod- elling and drug discovery. Nat Rev Drug Discov 10:915–929.

Hirt MN, Hansen A, Eschenhagen T.(2014) Cardiac tissue engi- neering: state of the art. Circ Res.114:354–367

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Morgan S. (2012) Book Chapter: From Microscopes to Stem

Cell Research: Discovering Regenerative Medicine.

Murry CE, Keller G (2008). Differentiation of embryonic stem cells to clinically relevant populations: lessons from embry- onic development. Cell;132:661–680.

Schugar RC, Robbins PD, Deasy BM (2008) Small molecules in stem cell self-renewal and differentiation. Gene Ther;15:126–135.

Sebastian D, Seung MJ, Lee J, Ju JH (2014) Recent techno- logical updates and clinical applications of induced pluripotent stem cells. Korean J. Int. Med; 29:547-557.

Takahashi K and Yamanaka S (2006). Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cul- tures by De"ned Factors, Cell, 126, 663–676.

Yamanaka S. (2012 ) Induced Pluripotent Stem Cells: Past, Present, and Future Stem Cell Volume 10, Issue 6, p678–684, 14 June 2012

Zaehres H, Scholer HR (2007). Induction of pluripotency: from mouse to human. Cell;131:834–835.