Stem Cells Lecture Notes PDF

Stem cells Prepared by Histology & Cell Biology department 1 What are stem cells? Why are they important? 2  Learning outcomes 1. Define stem cells. 2. Describe the characteristics of stem cells. 3. Classify stem cells 4. List Sources of stem c...

Stem cells Prepared by Histology & Cell Biology department 1 What are stem cells? Why are they important? 2  Learning outcomes 1. Define stem cells. 2. Describe the characteristics of stem cells. 3. Classify stem cells 4. List Sources of stem cells. 5. Distinguish points of similarities and differences between the types of stem cells. 6. Mention the medical applications of stem cells. 3 What are stem cells? ❑Stem cells are undifferentiated (unspecialized) cells that continuously divide. Nice to know ❑Their progenitors will: -Be stem cells or -Differentiate to a more specialized cell ❑So, stem cell can be defined as a cell that has dual ability of self-renewal and differentiation (production of different types of specialized cells). 4  Stem cells characteristics Self-Renewal Potency Ability of the cell to go through numerous It is the ability of stem cycles of cell divisions cells to differentiate while maintaining the into specialized cells undifferentiated state.  Other characters of the stem cells The nucleus of a stem cell Contains mainly euchromatin (active genes) and minimal heterochromatin. The cytoplasm contains Numerous polyribosomes mitochondria The number of stem cells in our body decreases with age Nice to know  Stem cells Where are they located? In stem cell niche It is an area in the tissue which provides a special microenvironment where stem cells are present in an undifferentiated and self-renewable state. Nice to know  Division of stem cells Symmetrical division Asymmetric division Stem cells give rise to Give rise to one daughter stem cell identical daughter stem and one progenitor cell (which cells. differentiates after division) It occurs mainly in early Occurs in later developmental stage embryonic life to and in adult. maintain stem cell population 9 Nice to know  Potency of Stem Cells Nice to know Totipotent Stem Cells Differentiate into embryonic & extraembryonic tissues. Pluripotent Stem Cells Differentiate into all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm Multipotent Stem Cells Differentiate into cell types that are of closely related family (e.g. C.T.) Stem cell ❑ In some organs (such as gut, bone marrow) stem cells regularly divide to repair and replace damaged tissues. ❑ In other organs (such as pancreas, liver) stem cells only divide under special conditions. 11 Normal differentiation pathways of adult stem cells ❑Epithelial stem cells in the lining of the gastrointestinal tract are located in deep crypts and give rise to enterocytes, goblet cells, Paneth cells and entero-endocrine cells. ❑Skin stem cells occur in the basal layer of the epidermis and at the base of hair follicles. Nice to know 12  Normal differentiation pathways of adult stem cells ❑Mesenchymal stem cells give rise to connective tissue cells such as bone cells (osteocytes), cartilage cells (chondrocytes), fat cells (adipocytes) Nice to know 13  Trans-differentiation Stem cells can shift from one line of differentiation to another line according to the surrounding microenvironment Nice to know  What are the main characters of all stem cells? 15 Stem cells characteristics: They are non-differentiated (unspecialized) cells. They have the ability to divide and renew themselves by cell division for long periods (long term self- renewal) Under certain physiological or experimental conditions they can be induced to become specialized cell types.  Types of stem cells 1- Embryonic stem cells 2- Adult stem cells. 3- Induced pluripotent stem cells 17  Types of stem cells Embryonic stem cells ▪ Human embryos (inner cell mass of Blastocyst) Nice to know 18 Embryonic stem cells are: 1) Pluripotent (they are able to differentiate into all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm) 2) Replicate indefinitely. However, their clinical use is limited because of ethical considerations and liability to form tumors (teratomas). 19 Embryonic stem cells Nice to know 20  Adult stem cells (Somatic): They are undifferentiated cells, found among differentiated cells in tissues or organs. They can divide and then differentiate (multipotent) to yield a specialized cells to maintain and repair the tissues in which they are found. 21  Adult Stem Cells Embryonic Stem Cells Origin Found among the differentiated cells Inner cell mass of embryo Differentiation Less undifferentiated Highly undifferentiated Renewal capacity Limited Unlimited Potency Multipotent Pluripotent Cells produced Produce limited number of cell types Produce all cell types Function Maintain tissues size Give rise to all cells of the body  Induced pluripotent stem cells (iPSCs) Are adult cells that have been genetically reprogrammed to become stem cell–like. Using genetic manipulation (viral transfection) expression of just four genes is sufficient to convert adult skin fibroblasts into iPSCs. Nice to know 23 Nice to know 24  Sources & Sites of stem cells Adult stem cells A) Bone marrow B) Umbilical cord blood C) Placental tissue D) Gastrointestinal tract E) Adipose tissue F) Skin G) Blood vessels (pericytes) H) Liver Nice to know 25  Bone marrow adult stem cells Two categories: Hematopoietic and Mesenchymal stem cells. - Hematopoietic stem cells differentiate into the different blood cells and are mainly found in the bone marrow. - Mesenchymal stem cells (MSCs) they can differentiate into fat cells, cartilage cells, bone cells, etc.) 26 Nice to know 27 Sources of MSCs Nice to know 28  Nice to know Growth in tissue culture: Adult stem cells are few in an adult tissue so their isolation, growth and multiplication in tissue culture is challenging. Embryonic stem cells can be grown relatively easily in tissue culture. 29 How are MSCs used in disease? Nice to know 30  Isolation of BM-MSCs Nice to know Cut away epiphyses of femurs & tibias. Flush out BM by syringe needle filled with medium. Centrifuge Wash with DMEM. Dissociate cells Count cells by hemocytometer. Culture in dish Stem cells in culture 32  Advantage of using MSCs in the therapeutic treatment 1- They are less immunogenic so they can be transplanted without graft rejection. 2- They cause no inflammation. 3-There is less evidence for malignant transformation. 33 True or False questions with the correction of false statement: 1- Embryonic stem cells are pluripotent and can differentiate into any cell type. ( T ) 2- Adult stem cells can become virtually any cell type in the body. ( F ) They are multipotent (several cell types) or unipotent. 3- Mesenchymal stem cells are immunogenic. ( F ) not immunogenic and so they can be transplanted without graft rejection 34  Medical applications of stem cells 1) They have the ability to replace damaged cells and treat diseases (cell-based therapies): Spinal cord injury burns ischemic heart diseases diabetes bone defects osteoarthritis Alzheimer disease Nice to know 35 Adding the right factors to get the needed cell type Nice to know 36 2) They could provide a resource for testing new medical treatments : New medications could be tested for safety on specialized cells generated in large numbers from stem cell lines – reducing the need for animal testing. 37 3) They could be used to study diseases: In many cases it is difficult to obtain the cells that are damaged in a disease, and to study them in detail. Scientists could use stem cells to model disease processes in the laboratory, and better understand what goes wrong. 38 What is meant by Cloning of human cells ? Cloning of human cells is a technology that holds the potential to cure many diseases and provide a source of exactly matched transplant tissues and organs. Nice to know 39  What is meant by Cloning of human cells ? By transferring adult cell DNA into an embryonic stem cell, it is possible to create a line of immortal embryonic cells that are able to develop into any type of adult cell, genetically identical to the donor. Nice to know 40  What are Cancer Stem Cells (CSCs)? They have the characteristics of other stem cells including self- renewal, proliferation, and differentiation to form the bulk of the tumor. They are believed to play a critical role in cancer initiation, maintenance, progression, drug resistance, and cancer recurrence or metastasis. Nice to know 41  References Oxford hand book of medical sciences 2 nd edition chapter 15 42 Thank you