Adult Stem Cells as Regenerative Medicine Kanika Varma1, Parul Rewari1, Jayanti Tokas1, Rubina Begum1, Shalini Jain2 and Hariom Yadav2 1Department of Biotechnology, JMIT, Radaur, Haryana, India 2NIDDK, National Institutes of Health, Bethesda, MD 20892, USA Email: yadavhariom@gmail.com

Adult Stem Cell Undifferentiated Cells Found throughout the body after embryonic development Multiply by cell division to replenish dying cells Regenerate Damaged Tissues.

Types of Adult Stem Cells Hematopoietic Mammary Mesenchymal Neural Endothelial Olfactory Neural crest Testicular

Properties Defining properties- self-renewal & potency Lineage Signaling pathways Multidrug resistance Plasticity / Transdifferentiation Properties of adult stem cells 2.1.1 Defining properties Self-renewal which is the ability to go through numerous cycles of cell division while maintaining the undifferentiated state. Multipotency or multidifferentiative potential which is the ability to generate progeny of several distinct cell types, (for example glial cells and neurons) as opposed to unipotency which is the term for cells that are restricted to producing a single-cell type. These properties can be shown with relative ease in vitro using methods such as clonogenic assays, where the progeny of a single cell is characterized, however, it is known that in vitro cell culture conditions can alter the behavior of cells. Proving that a particular subpopulation of cells possesses stem cell properties in vivo is challenging. 2.1.2 Lineage To ensure self-renewal, stem cells undergo two types of cell division,one is Symmetric division gives rise to two identical daughter cells, both endowed with stem cell properties, whereas asymmetric division produces only one stem cell and a progenitor cells with limited self-renewal potential. Asymmetric division is the process of a cell splitting into another cell and an essential cell fat, or a lipid , this lipid will bond to a free cell and reproduce. Progenitors can go through several rounds of cell division before finally differentiating into a mature cell. The molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as receptors) between the daughter cells. 2.1.3 Signaling pathways Adult stem cell research has been focused on uncovering the general molecular mechanisms that control their self-renewal and differentiation. Eg: Bmi-1 , Notch , Wnt. These developmental pathways are also strongly implicated as stem cell regulators.(Beachy et al,2004). 2.1.4 Multidrug resistance Adult stem cells express transporters of the ATP-binding cassette family that actively pump a diversity of organic molecules out of the cell.(Chaudhary and Roninson,1991). Many pharmaceuticals are exported by these transporters conferring multidrug resistance onto the cell. This complicates the design of drugs, for instance neural stem cells targeted therapies for the treatment of clinical depression. 2.1.5 Plasticity Under special conditions tissue-specific adult stem cells can generate a whole spectrum of cell types of other tissues, even crossing germ layers.(Filip et al,2004). This phenomenon is referred to as stem cell transdifferentiation or plasticity. It can be induced by modifying the growth medium when stem cells are cultured in vitro or transplanting them to an organ of the body different from the one they were originally isolated from.

Location of Adult Stem Cell Identified in many organs and tissues - Brain, Bone marrow , Peripheral blood, Blood vessels, Skeletal muscle, Skin, Teeth, Heart, Gut, Liver, Ovarian epithelium and Testis Thought to reside in a specific area of each tissue - a ‘stem cell niche’

Plasticity Basis for generating tissue for transplantation Differentiate into cell types in organs / tissues other than those expected from the cells predicted lineage

Stem Cells in the Bone Marrow and Blood Three types of stem cell originate in bone marrow: Hematopoietic Stem Cell Stromal Cells Endothelial Progenitor Cells

In Other Tissues Endothelial Progenitor Cells Skeletal Muscle Stem Cells Epithelial Cell Precursors in the Skin and Digestive System Stem Cells in the Pancreas and Liver

Hematopoietic and Stromal Adult Stem Cell Differentiation Hematopoietic stem cells give rise to all the types of blood cells: red blood cells, B lymphocytes, T lymphocytes, natural killer cells, neutrophils, basophils, eosinophils, monocytes, and macrophages. Mesenchymal stem cells give rise to a variety of cell types: bone cells (osteocytes), cartilage cells (chondrocytes), fat cells (adipocytes), and other kinds of connective tissue cells such as those in tendons. Neural stem cells in the brain give rise to its three major cell types: nerve cells (neurons) and two categories of non-neuronal cells—astrocytes and oligodendrocytes. Epithelial stem cells in the lining of the digestive tract occur in deep crypts and give rise to several cell types: absorptive cells, goblet cells, paneth cells, and enteroendocrine cells. Skin stem cells occur in the basal layer of the epidermis and at the base of hair follicles. The epidermal stem cells give rise to keratinocytes, which migrate to the surface of the skin and form a protective layer. The follicular stem cells can give rise to both the hair follicle and to the epidermis. stemcells.nih.gov/.../images/figure2_lg.jpg

Adult Stem Cell Therapies The therapies require a stem cell source of the specific lineage and harvesting or culturing them up to the numbers required is a challenge.

Regenerative Medicine Process of creating living, functional tissues to repair or replace tissue or organ function lost due to age, disease, damage, or congenital defects It helps to produce extended healthy longevity,

Potential of Adult Stem Cells

Treating Leukemia Leukemia results when white blood cells made in bone marrow begin to grow and function abnormally One way to do this is through chemotherapy When chemotherapy cannot solve the problem, doctors turn to bone marrow transplants.

Another Stem Cell Victory - Parkinson's Disease A degenerative disorder of the central nervous system Sufferers lack a sufficient amount of a brain chemical called dopamine The cure of this disease is to multiply cells that release dopamine

Insulin Independence There is insulin independence for Type 1 diabetes patients A study showed patients receiving injections with adult stem cells were able to go as long as four years without having to rely on insulin shots.

Heeling of Heart by Adult Stem Cells Cardiologists and heart surgeons worldwide currently use VesCell™ adult stem cell therapy to treat patients suffering from coronary artery disease, cardiomyopathy, and congestive heart failure.

Process of stem cells for spinal cord injury Bone Marrow taken from the hip 6 weeks of cultivating the adult stem cells to increase total to 100 million. Adult Stem Cells injected at injury site (C3-C4) in a surgical procedure

Thalesemia The genetic defect results in reduced rate of synthesis of one of the globin chains that make up hemoglobin Hematopoietic stem cell transplantation (HSCT) is the only curative approach

Curing cancer Cancer stem cells (CSCs) are cancer cells (found within tumors or hematological cancers) that possess characteristics associated with normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer sample Lisa Ray to undergo stem cell transplant for blood cancer Knoxville Times – Wednesday 18th November, 2009   – (IANS) Indo-Canadian actress Lisa Ray will undergo a stem cell transplant to treat her multiple myeloma, an incurable form of blood cancer.  The 37-year-old star was diagnosed with the cancer of the bone marrow in June and has been undergoing chemotherapy since July. Toronto-born Lisa made this announcement Tuesday while visiting the Marshall McLuhan Catholic Secondary School where her film ‘Water’, directed by Deepa Mehta, was screened. Ray, who was born to a Polish mother and Bengali father, said the process for a stem cell transplant would begin next week in a city hospital.  The procedure would begin by releasing her own stem cells into her blood, then collecting them and later freezing them, she said.  Calling it a ‘reboot’ of her system, she said the process would take up to two weeks to complete.  After this, she would put on a waiting list for a stem cell transplant.

Benefits of Adult Stem Cell Research Easy to obtain Potentially limitless in supply Patients can use their own stem cells for treatment and therapy Adult stem cells are politically neutral Not offensive to any major interest group nor do they generate controversy.

Limitations of adult stem cell The isolation of some types of ASC, for example the isolation of neural cells from a patient's brain, would be impractical Where a person suffers from a genetic disorder or some types of cancers, ASC isolated from that individual will retain the damaging genetic alterations underlying the disease and so be of little therapeutic value Unambiguous identification is difficult Maintenance in culture is difficult

Conclusion Adult stem cell research is complicated and rapidly changing .Today’s medicine generally tries to support or treat injured tissues and organs, but stem cells may someday simply replace them.

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