Basic biology of stem cells

A brief biology of stem cell , it's potency and sources

1. BASIC BIOLOGY OF STEM CELLS

2. STEM CELL – DEFINITION Stem cells are undifferentiated mass of cells that has the ability to continuously divide and differentiate (develop) into various other kind(s) of cells/tissues. The human body has a variety of 220 different cells types. Stem cells are master cells that act as foundation cells for every organ, tissue and cell in the body.. They are considered as a blank microchip that can be programmed to perform particular tasks. They serve as a repair machine for the body.

3. Stem Cell Characteristics ‘Blank cells’ (unspecialized) Capable of dividing and renewing themselves for long periods of time (proliferation and renewal) Have the potential to give rise to specialized cell types (differentiation)

4. CLASSIFICATION OF STEM CELLS based on potency Stem cells can be classified into four broad categories, based on their ability to differentiate Totipotent stem cells are found only in early embryos. Each cell can form a complete organism (1-3 days) . Pluripotent stem cells exist in the undifferentiated inner cell mass of the blastocyst (5 to 14 days) and can form any of the over 200 different cell types found in the body. stem cells can form most or all cell types in the adult Multipotent stem cells are derived from fetal tissue, cord blood, and adult stem cells. These cells are differentiated, but can form a number of other tissues. stem cells can form multiple types of cells and tissue types Unipotent are able to contribute to only one mature cell type but have the property of self-renewal which distinguishes them from non-stem cells

5. A life story… TOTIPOTENCY

6. Pluripotent stem cells – more potential to become any type of cell

7. Multipotent stem cells – limited in what the cells can become

8. The classical definition of a stem cell requires that it possess two properties: Self-renewal: the ability to go through numerous cycles of cell division while maintaining the undifferentiated state. Potency: the capacity to differentiate into specialized cell types. In the strictest sense, this requires stem cells to be either totipotent or pluripotent—to be able to give rise to any mature cell type, although multipotent or unipotent progenitor cells are sometimes referred to as stem cells. Apart from this it is said that stem cell function is regulated in a feed back mechanism.

9. SELF-RENEWAL Two mechanisms exist to ensure that a stem cell population is maintained: Obligatory asymmetric replication : a stem cell divides into one mother cell that is identical to the original stem cell, and another daughter cell that is differentiated Stochastic differentiation: when one stem cell develops into two differentiated daughter cells, another stem cell undergoes mitosis and produces two stem cells identical to the original. Potency definitions

10. Stem cell differentiation and proliferation 1 : symmetric stem cell division; 2 : asymmetric stem cell division; 3 : progenitor division; 4 : terminal differentiation A: stem cell; B: progenitor cell; C: differentiated cell;

11. Difference between stem cell and progenitor cell

12. Embryonic stem cells •five to six-day-old embryo •Tabula rasa Embryonic germ cells •derived from the part of a human embryo or fetus that will ultimately produce eggs or sperm (gametes). Adult stem cells •undifferentiated cells found among specialized or differentiated cells in a tissue or organ after birth •appear to have a more restricted ability to produce different cell types and to self-renew. Further classification

13. Embryonic stem cells Cells found early (less than 2 wks.) in the development of an embryo Embryonic stem cells are the most versatile because they can become any cell in the body including fetal stem cells and adult stem cells. Embryonic stem (ES) cells are taken from inside the blastocyst, a very early stage embryo. The blastocyst is a ball of about 50-100 cells and it is not yet implanted in the womb. It is made up of an outer layer of cells, a fluid-filled space and a group of cells called the inner cell mass. ES cells are found in the inner cell mass.

14. Isolation of Human Embryonic Stem Cells

15. In vitro fertilization technique

16. Cleavage 8 cell stage Blastocyst Blastocyst inner cell mass Stages of embryogenesis

17. Embryonic germ cells Human embryonic germ cell (EG cells) normally develop into eggs and sperm. They are derived from a specific part of the embryo called the gonad ridge, and are isolated from fetuses older than 8 weeks of development. One advantage of embryonic germ cells cells is that they do not appear to generate tumors when transferred into the body, as embryonic stem cells do.  One of the greatest issues facing researchers is that the derivation of EG cells results from the destruction of a foetus . EG cells are isolated from terminated pregnancies and no embryos or foetuses are created for research purposes.

18. ADULT STEM CELLS Adult stem cells are found in the human body and in umbilical cord blood. The most well known source of adult stem cells in the body is bone marrow but they are also found in many organs and tissues; even in the blood. Adult stem cells are more specialized since they are assigned to a specific cell family such as blood cells, nerve cells, etc. Recently, it was discovered that an adult stem cell from one tissue may act as a stem cell for another tissue, i.e. blood to neural

19. Adult Stem Cells An undifferentiated cells found among specialized or differentiated cells in a tissue or organ after birth

20. Also Known as Wharton‟s Jelly Adult stem cells of infant origin Less invasive than bone marrow Greater compatibility Less expensive Umbilical cord stem cells

21. Umbilical cord stem cells Three important functions: 1. Plasticity : Potential to change into other cell types like nerve cells 2. Homing : To travel to the site of tissue damage 3. Engraftment : To unite with other tissues

22. HEMATOPOIETIC STEM CELLS Hematopoietic stem cells are those cells from where all blood cells originate. Discovery of hematopoietic stem cells in cord blood was made in the year 1974. In the year 1982 Broxmeyer suggested umbilical cord blood contained significant amount of hematopoietic stem cells suitable for transplantation Pluripotent :- red cells, white cells and platelets High proliferative capacity : 1 cell in a million

23. Sources of hematopoietic stem cells in human Umbilical Cord blood. Peripheral blood. Bone marrow

24. Mesenchymal Stem Cells Mesenchymal stem cells (MSCs) , also called bone marrow stromal cells , are multipotent stem cells that differentiate into a variety of cell types, including: − osteoblasts (bone cells) − chondrocytes (cartilage cells) − adipocytes (fat cells).

25. Human MSCs are of interest in clinical applications due to: −Capacity for homing and engraftment −Wide-range differentiation potential −Immunosuppressive attributes Potential MSC Therapies: −Graft versus Host Disease − Crohn’s Disease −Bone Defects/ Genetic Disease −HSC Transplantation −Cardiac repair −Trachea repair

26. Induced pluripotent stem cells ( iPSCs ) adult cells that have been genetically reprogrammed to an embryonic stem cell–like state by being forced to express genes and factors important for maintaining the defining properties of embryonic stem cells

27. Why the Controversy Over Stem cells? •Embryonic Stem cells are derived from extra blastocysts that would otherwise be discarded following IVF. •Extracting stem cells destroys the developing blastocyst (embryo). - Questions for Consideration- •Is an embryo a person? •Is it morally acceptable to use embryos for research? •When do we become “human beings?”

28. Reference “STEM CELLS” by C.S.Potten