Original Article Stem : Basics, Classification and Applications

K. Kalra* and P.C. Tomar

Assistant Professor, Department of Engineering, Faculty of Engineering and Technology, Manav Rachna International University, Sector –43, Aravalli Hills, Delhi-Surajkund road, Faridabad, Haryana-121004, India

ABSTRACT

Stem cells are unspecialized cells that develop into the specialized cells that make up the different types of tissue in the .They are characterized by the ability to renew themselves through mitotic and differentiating into a diverse range Address for of specialized cell types. They are vital to the development, growth, Correspondence maintenance, and repair of our , , muscles, , blood, , and other organs .Stem cells are found in all of us, from the Assistant Professor, early stages of human development to the end of life. Department of research holds tremendous promise for the development of novel Biotechnology for many serious diseases and injuries. While stem cell- Engineering, Faculty of based treatments have been established as a clinical standard of care Engineering and for some conditions, such as transplants for Technology, Manav leukemia and epithelial stem cell-based treatments for burns and Rachna International corneal disorders, the scope of potential stem cell-based therapies has University, Sector –43, expanded in recent years due to advances in stem cell research. It has Aravalli Hills, Delhi- been only recently that scientists have understood stem cells well Surajkund road, enough to consider the possibilities of growing them outside the body Faridabad, Haryana- for long periods of time. With that advance, rigorous experiments can 121004, India. be conducted, and the possibility of manipulating these cells in such a E-mail: way that specific tissues can be grown is real. [email protected] Keywords : Stem cell, Treatment, , Research.

INTRODUCTION Stem cells are defined as cells that having the potency to differentiate into wide have clonogenic and self-renewing range of adult cells 1. Self renewal and capabilities and differentiate into multiple totipotency are characteristic of stem cell. cell lineages. Stem cells are found in all of Though totipotency is shown by very early us, from the early stages of human embryonic stem cells, the adult stem cells development to the end of life. Stem cells possess multipotency and differential are basic cells of all multicellular organisms plasticity which can be exploited for future

American Journal of Phytomedicine and Clinical Therapeutics www.ajpct.org Kalra et al______ISSN 2321 – 2748 generation of therapeutic options 2. All stem 1800's with the discovery that some cells cells may prove useful for medical research, could generate other cells. In the early but each of the different types has both 1900's the first real stem cells were promise and limitations 3. discovered when it was found that some For decades, researchers have been cells generate blood cells. The term "stem studying the of stem cells to figure cell" was proposed for scientific use by the out how development works and to find new Russian histologist Alexander Maksimov in ways of treating health problems 4. The 1908. marrow transplant between two scientific researchers and medical doctors of siblings successfully treated SCID in 1968. today hope to make the legendary concept of Haemopoietic stem cells were discovered in into reality by developing human in 1978 8. therapies to restore lost, damaged, or aging James Thomson and coworkers cells and tissues in the human body 5. This derived the first human research has opened new horizons for stem line at the University of Wisconsin–Madison cell research. in 1998 8. More recently, in 2005, scientists Stem cell research holds tremendous at Kingston University in England were promise for the development of novel purported to have found another category of therapies for many serious diseases and stem cells. These were named cord blood injuries. While stem cell-based treatments embryonic-like stem cells, which originate have been established as a clinical standard in blood. Korean researcher of care for some conditions, such as Hwang Woo-Suk (2004–2005) claimed to hematopoietic stem cell transplants for have created several human embryonic stem leukemia and epithelial stem cell-based cell lines from unfertilised human oocytes 9. treatments for burns and corneal disorders, Scientists at Newcastle University in the scope of potential stem cell-based England create the first ever artificial therapies has expanded in recent years due cells using umbilical cord blood stem cells to advances in stem cell research 6. It is in October 2006 10,11 . It is suggested that impossible to project when actual treatments these stem cells have the ability to or cures might emerge from such research, differentiate into more cell types than adult but the paths this research might take and stem cells, opening up greater possibilities potential applications have been much for cell-based therapies. Then, in early 2007, discussed 7. Stem cells can now be grown researchers led by Dr. and transformed into specialized cells with claimed that a new type of stem cell had characteristics consistent with cells of been isolated in 12 . This various tissues such as muscles or nerves finding is particularly important because through . Highly plastic adult these stem cells could prove to be a viable stem cells from a variety of sources, alternative to the controversial use of including umbilical cord blood and bone embryonic stem cells 13 . Mario Capecchi, marrow, are routinely used in medical , and Oliver Smithies won the therapies. This review focuses on types of 2007 Nobel Prize for Physiology or stem cells, their sources, stem cell research Medicine for their work on embryonic stem and future aspects 7. cells from mice using targeting strategies producing genetically engineered Historical perspectives mice (known as knockout mice) for gene The history of stem cell research had research 14 . a benign, embryonic beginning in the mid

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The first published study of bones, muscles, nerves, blood, skin, and successful regeneration in the other organs 3. human knee using autologous adult Laboratory studies of stem cells mesenchymal stem cells is published by enable scientists to learn about the cells’ clinicians from Regenerative Sciences in essential properties and what makes them 2008 15 . Embryonic stem cell isolated from a different from specialized cell types. single human was reported in 2008 16 . Scientists are already using stem cells in the Australian scientists (2009) found a way to laboratory to screen new drugs and to improve of mouse muscle develop model systems to study normal stem cells 17 . Kim et al . 2009 18 . Announced growth and identify the causes of birth that they had devised a way to manipulate defects 20 . Research on stem cells continues skin cells to create patient specific "induced to advance knowledge about how an pluripotent stem cells" (iPS), claiming it to organism develops from a single cell and be the 'ultimate stem cell solution’. For the how healthy cells replace damaged cells in first time, human embryonic stem cells have adult organisms. Stem cell research is one of been cultured under chemically controlled the most fascinating areas of contemporary conditions without the use of animal biology, but, as with many expanding fields substances, which is essential for future of scientific inquiry, research on stem cells clinical uses in 2010 19 . raises scientific questions as rapidly as it Over the last few years, national generates new discoveries 21 . Over the past policies and debate amongst the public as year, adult stem cells have been used either well as religious groups, government exclusively or in combination with other officials and scientists have led to various treatments to achieve significant "healthcare laws and procedures regarding stem cell benefits" for sufferers of the every tissue of harvesting, development and treatment for human body (Fig.-2) 22,23 . research or disease purposes. The goals of such policies are to safeguard the public Classification of stem cells on the basis of from unethical stem cell research and use potency while still supporting new advancements in Stem cells can be classified by the the field. extent to which they can differentiate into different cell types. These four main Stem cell classifications are totipotent, pluripotent, A stem cell is a non-specialized, multipotent, or unipotent. generic cell which can make exact copies of itself indefinitely and can differentiate and Totipotent produce specialized cells for the various The ability to differentiate into all tissues of the body 2 .Stem cells are cells possible cell types (Fig-3). Examples are the found in most, if not all, multi-cellular formed at egg fertilization and the organisms. They are characterized by self- first few cells that result from the division of renewal and potency i.e. - the ability to the zygote. renew themselves through mitotic cell division and differentiating into a diverse Pluripotent range of specialized cell types 2 (Fig. 1). The ability to differentiate into They are vital to the development, growth, almost all cell types. Examples include maintenance, and repair of our brains, embryonic stem cells and cells that are derived from the , , and

AJPCT[2][7][2014]919-930 Kalra et al______ISSN 2321 – 2748 germ layers that are formed in the Adult stem cells beginning stages of embryonic stem cell Adult stem cells are undifferentiated differentiation. totipotent or multipotent cells, found throughout the body after embryonic Multipotent development, that multiply by cell division The ability to differentiate into a to replenish dying cells and regenerate closely related family of cells. Examples damaged tissues. (Fig.-4). The primary roles include hematopoietic (adult) stem cells that of adult stem cells in a living organism are can become red and white blood cells or to maintain and repair the tissue in which platelets. they are found. Unlike embryonic stem cells, which are defined by their origin (the inner Oligopotent cell mass of the ), the origin of The ability to differentiate into a few adult stem cells in some mature tissues is cells. Examples include (adult) lymphoid or still under investigation 28 . myeloid stem cells. Pluripotent stem cells i Unipotent Recently, a third type of stem cell, The ability to only produce cells of with properties similar to embryonic stem their own type, but have the property of self- cells, has emerged. Scientists have renewal required to be labeled a stem cell. engineered these induced pluripotent stem Examples include (adult) muscle stem cells i (iPS cells) by manipulating the cells 24 . expression of certain - '' cells back to a Classification of stem cells on the basis of pluripotent state 29-31 . their sources The easiest way to categorize stem Stem cell culture cells is by dividing them into two types: Growing cells in the laboratory is Early or embryonic and mature or adult. known as cell culture. Human embryonic Early stem cells, often called embryonic stem cells (hESCs) are generated by stem cells, are found in the transferring cells from a preimplantation- of a blastocyst after approximately five days stage into a plastic laboratory of development. Mature stem cells are found culture dish that contains a nutrient broth in specific mature body tissues as well as the known as culture medium. The cells divide umbilical cord and after birth 25 . and spread over the surface of the dish. However, if the plated cells survive, divide Embryonic stem cells and multiply enough to crowd the dish, they Embryonic stem cells are self- are removed gently and plated into several replicating pluripotent cells that are fresh culture dishes. The process of re- potentially immortal 26 . They are derived plating or sub culturing the cells is repeated from at a developmental stage many times and for many months. Each before the time of implantation would cycle of subculturing the cells is referred to normally occur in the uterus 2. The embryos as a passage. Once the cell line is from which human embryonic stem cells are established, the original cells yield millions derived are typically four or five days old of embryonic stem cells (Fig. 5). Embryonic and are a hollow microscopic ball of cells stem cells that have proliferated in cell called the blastocyst 27 . culture for six or more months without

AJPCT[2][7][2014]919-930 Kalra et al______ISSN 2321 – 2748 differentiating, are pluripotent, and appear Celiac Disease, cardiac failure, muscle genetically normal are referred to as an damage and neurological disorders, and embryonic stem cell line. At any stage in the many others 34 . They have suggested that process, batches of cells can be frozen and before stem cell therapeutics can be applied shipped to other laboratories for further in the clinical setting, more research is culture and experimentation 32 . necessary to understand stem cell behavior upon transplantation as well as the Stem cell lines mechanisms of stem cell interaction with the A stem cell line is a family of diseased/injured microenvironment. constantly dividing cells, the product of a transplants (BMT) are single parent group of stem cells. They are a well known clinical application of stem obtained from human or animal tissues and cell transplantation. BMT can repopulate the can replicate for long periods of time marrow and restore all the different cell ("within glass"; or, commonly, "in the lab", types of the blood after high doses of in an artificial environment). They are chemotherapy and/or radiotherapy, our main frequently used for research relating to defense used to eliminate endogenous embryonic stem cells or entire cells. The isolation of additional stem organism (Fig. 5). Once stem cells have and progenitors cells is now being been allowed to divide and propagate in a developed for many other clinical controlled culture, the collection of healthy, applications. Several are described below. dividing, and undifferentiated cells is called a stem cell line 33 . Skin replacement The knowledge of stem cells has Applications of stem cells made it possible for scientists to grow skin The goal of any stem cell therapy is from a patient’s plucked hair. Skin to repair a damaged tissue that can't heal () stem cells reside in the hair itself. Ongoing research on stem cell follicle and can be removed when a hair is therapies gives hope to patients who would plucked 35 . These cells can be cultured to normally not receive treatment to cure their form an epidermal equivalent of the patients disease but just to alleviate the symptoms of own skin and provides tissue for an their chronic illness. Stem cell therapies autologous graft, bypassing the problem of involve more than simply transplanting cells rejection. into the body and directing them to grow new, healthy tissue. It may also be possible cell transplantation to coax stem cells already in the body to Stem cells can provide dopamine - a work overtime and produce new tissue. chemical lacking in victims of Parkinson’s disease. It involves the loss of cells which Possible treatments by stem cells produce the neurotransmitter dopamine. The A number of stem cell therapeutics first double-blind study of fetal cell exist, but most are at experimental stages transplants for Parkinson’s disease reported and/or costly, with the notable exception of survival and release of dopamine from the bone marrow transplantation (Fig. 6). transplanted cells and a functional Medical researchers anticipate that adult and improvement of clinical symptoms 36 . embryonic stem cells will soon be able to However, some patients developed side treat cancer, Type 1 mellitus, effects, which suggested that there was an Parkinson's disease, Huntington's disease, over sensitization to or too much dopamine.

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Figure 1. Characters of stem cell: replication and differentiation

Figure 2. Healthcare benefits for every tissue of human body

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Figure 3. Classification of stem cell on basis of potency

Figure 4. Sources of adult stem cells

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Figure 5. Stem cell culture and stem cell lines

Figure 6. Possible treatments by stem cells

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