Stem cells.pdf

Stem cells Stem cells Stem Cell Unspecialized cell with the capacity for: Self Renewal (finite in-vivo) Asymmetric division Transformation into other mature cell types (potency) Classifications of stem cells/Source Embryonic stem cells are pluripotent and can give rise to...

Stem cells Stem cells Stem Cell Unspecialized cell with the capacity for: Self Renewal (finite in-vivo) Asymmetric division Transformation into other mature cell types (potency) Classifications of stem cells/Source Embryonic stem cells are pluripotent and can give rise to all types of cells in the body Adult stem cells are only multipotent and are more limited in the types of cells that they can give rise to. Stem Cell Potency Progenitor Cell Step between Stem Cell and specialized cell Capable of differentiation but not self-renewal Pluripotent Stem Cell Capable of differentiating into all Adult Stem Cell types Able to form cells of all 3 germ layers: mesoderm, ectoderm and endoderm Unable to give rise to placental or embryo cells. Embryonic Stem Cells Derived from the inner cell mass of developing blastocysts They are Pluripotent stem cells Self-renewal in-vivo and in-vitro Pluripotency stem cell (PSC) Markers: OCT3/4, Nanog, Sox2, SSEA4, TRA1-81 and TRA1-60 Gives rise to cells from all 3 germ layers; ectoderm, endoderm and mesoderm. Teratoma formation: the capability to differentiate into all three germ layers spontaneously in vivo. Immortal in vitro: they can divide unlimitedly. First isolated by Thomson and Jones in 1998 Over 400 ESC lines developed. Comparison : Pluripotent vs Multipotent Multipotent Stem Cell Capable of differentiating into multiple but limited number of cell lines. Most adult stem cells are multipotent Examples: HSC, MSC, Neural Stem Cells Unipotent Stem Cell Capable of differentiating along one cell line only. Example: Adult Stem Cell in differentiated tissue Induced Pluripotent Stem Cells (iPSCs) Genetically modified adult cells to resemble embryonic-like SCs May substitute for ESCs Discovered in 2006 by Prof. Yamanaka and Takahashi, Nobel Prize Potential for mutagenesis Induced Pluripotent Stem Cells (iPSCs) Yamanaka Factors Oct4, Sox2, Klf4, c-Myc Oct4 and Sox2 are Core Factors Klf4 enhances core factor developmental regulation C-Myc regulates metabolism Highly expressed in ESCs Developmental signaling network of ESCs Determinant of ESC pluripotency Adult Stem Cells 1. Non-Embryonic Stem Cell 2. Also referred to as “Somatic Stem Cell” 3. Not “adult”, rather “post- embryonic” Stem cell 1. Fetal Stem Cells are Adult Stem Cells 4. Mostly multipotent, rather than pluripotent 1. Limited differentiation potential 2. Capacity for self-renewal 5. Examples HSC MSC Fibroblast SC Hematopoietic Stem Cell (HSC) Derived from Mesoderm Multipotent Able to give rise to all Blood Cells (lymphoid, myeloid) Location Adult Bone Marrow Peripheral Blood Umbilical Cord Blood Mesenchymal Stem Cell Multipotent Traditionally found in red bone marrow (Stromal MSC) Other locations Adipose Tissue Peripheral Blood Umbilical cord blood( UCB) Dental tissues Differentiation potential: Adipocytes Chondrocytes Tenocytes Osteocytes Myocytes Mesenchymal Stem Cells 1. Multipotent 2. Stromal (BM) origin 3. Can be isolated from almost all tissue 4. Perivascular niche locations 5. Trophic support (helper molecules, essential for growth and development) 6. Immune regulation 7. In Vitro Differentiation potential: Adipocytes Chondrocytes Osteocyte Myocytes Tenocytes Mesenchymal Stem Cells 1. Surface Antigens according to the international society of celullar transplant( ISCT) : ≥ 95% Positive: CD105, CD73, CD90 and ≤ 2% Negative: CD45, CD34, CD14, CD19, HLA-DR. 2. Affinity for plastic adherence (isolation technique) 3. Easy in-vitro expansion 4. High plasticity 5. Immune privileged 6. Immunomodulatory effects via cytokine secretion 7. Can be isolated from any vascular tissue. Hematopoietic Stem Cells(HSCs) 1. Multipotent (moderate plasticity) 2. Derived from Mesoderm 3. Able to give rise to all Blood Cells (lymphoid, myeloid) Hematopoietic Stem and Progenitor Cell (HSPC) Limited transdifferentiation potential (muscle, liver, bone) Located in Adult Bone Marrow Peripheral Blood Umbilical Cord Blood  Adipose-Derived Stem Cells Meet majority of ISCT criteria for MSCs CD31- CD34+ CD45- CD90+ CD105- CD146- Reside in the capillary and adventitia of blood vessels Coexist with pericytes and endothelial cells In large blood vessels, ADSCs exist as specialized fibroblasts  Umbilical Cord Blood Umbilical Cord Blood (UCB) vs Adult Peripheral Blood (APB) UCB Cell Populations Primary cell population: lymphocytes, monocytes High Natural killer (NK ) population Lower T-lymphocyte population Higher proportion of immature T-lymphocytes Lower absolute numbers of Cytokines. Presumption: Higher ratio of Anti- vs. Pro-Inflammatory Early in embryogenesis, HSCs and MSCs migrate from the Cytokines yolk sac and aorta-gonad-mesonephros to the placenta and then back to the fetal liver and bone marrow through the Low immunogenic cells. umbilical cord. During these two migration waves, some cells are trapped in Wharton's jelly and are retained therein throughout the whole period of gestation. Umbilical Cord Blood (MSCs): 1. First isolated from Wharton’s jelly 1. Substance of UC 2. Mesodermal origin 2. High telomerase activity 3. Lower number than BM-MSCs 4. Higher proliferative potential than BM-MSCs 5. High differentiation potential 6. Lack of apparent tumorigenicity 7. High immunomodulatory activity Amniotic Fluid Stem Cells Likely released from fetal amniotic membrane, embryonic skin, digestive tract, and the respiratory and urogenital systems Heterogeneous population 1. Some pluripotent markers (OCT4 and SSEA4) 2. Some somatic markers: CD29, CD44, CD73, CD90, and CD105 3. Differentiation into all 3 germ layers 4. MSC features 5. Potent Paracrine effects 6. High proliferation rate 7. Non-tumorigenic Stem Cells of Dental Origin Dental Mesenchymal Stem Cells: Locations 3rd molar Incisors Deciduous Origin Ectomesenchyme. Neural Crest High neural regenerative potential Neurotrophic factor secretion  Dental stem cells 1. Dental Pulp Stem Cells (DPSC) 2. Stem Cells from Human Exfoliated Deciduous Teeth (SHED) 3. Stem Cells from Apical Papilla (SCAP) 4. Dental follicle stem cells (DFSCs). 5. Periodontal ligament stem cells (PDLSCs). 6. Gingival fibroblast stem cells (GFSCs). 7. Alveolar bone marrow –derived stem cells (ABMSCs). Uses of dental stem cells in dental tissue regeneration  Cancer Stem Cells 1. Tumorigenic 2. Tumor fraction 3. Component of non-solid and solid tumors 1. Solid tumor CSC discovery in glioma (2002) 4. Similar characteristics to normal Stem Cells 1. Self Renewal 2. Differentiation (Mutagenesis) 5. Limited tumor regression 6. Metastasis Tumor hierarchy model