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Questions and Answers
What role do T-cells primarily play in the immune system?
What role do T-cells primarily play in the immune system?
Which organ is primarily responsible for the maturation of T-lymphocytes?
Which organ is primarily responsible for the maturation of T-lymphocytes?
Which of the following statements about endothelial growth factors is true?
Which of the following statements about endothelial growth factors is true?
In the dermis layer of the skin, which type of cells are primarily responsible for immune response?
In the dermis layer of the skin, which type of cells are primarily responsible for immune response?
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What is the main function of iPSC cells in research?
What is the main function of iPSC cells in research?
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Which cells are produced in the bone marrow?
Which cells are produced in the bone marrow?
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Thymus is responsible for producing erythrocytes.
Thymus is responsible for producing erythrocytes.
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What is the main function of lymphocytes?
What is the main function of lymphocytes?
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The ______ is primarily involved in the maturation of T-cells.
The ______ is primarily involved in the maturation of T-cells.
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What are iPS cells?
What are iPS cells?
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What is a primary function of iPSC cells?
What is a primary function of iPSC cells?
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Which of the following correctly describes T-lymphocytes?
Which of the following correctly describes T-lymphocytes?
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Which layer of skin is primarily involved in immune response?
Which layer of skin is primarily involved in immune response?
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What factor contributes to the function of endothelial cells in blood vessels?
What factor contributes to the function of endothelial cells in blood vessels?
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Which statement about bone marrow is correct?
Which statement about bone marrow is correct?
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Study Notes
Learning Objectives
- Students should be able to discuss stem cell function
- Students should be able to identify different types of stem cells
- Students should understand the medical applications of stem cells
Introduction
- Cell proliferation and death are balanced throughout the life of multicellular organisms.
- Homeostasis is the balance between cell death and proliferation.
- Apoptosis and necrosis are forms of cell death.
- Development begins with rapid proliferation of embryonic cells.
- Cells differentiate to form tissues and organs.
- The human body comprises 1014 cells with 200 differentiated cell types.
- All cells originate from a single cell.
Introduction: Different Cells
- As cells differentiate the rate of proliferation decreases.
- Cells arrest in the G0 phase of the cell cycle.
- Cells are lost due to injury or programmed cell death.
- Tissues contain cells able to proliferate to replace cells lost.
- Some tissues have high rates of turnover.
- Some differentiated cells retain the ability to divide and re-enter the cell cycle.
- Most differentiated cells are unable to proliferate.
- The proliferation of less differentiated cells, such as stem cells accounts for the replacement of cells.
Proliferation of Differentiated Cells
- Fibroblasts, skin fibroblasts, and endothelial cells are examples of cells that retain the ability to divide.
- Some internal organs like the liver can also regenerate.
Proliferation of Differentiated Cells : Fibroblasts
- Skin fibroblasts normally arrest in G0.
- Fibroblasts rapidly proliferate in response to repair of injury (like cuts or wounds).
- Blood clotting releases platelet-derived growth factor (PDGF)
- PDGF stimulates the proliferation and migration of fibroblasts.
- Fibroblasts repair and regrow damaged tissues.
Proliferation of Differentiated Cells : Endothelial Cells
- Endothelial cells remain capable of proliferation.
- Endothelial cells form new blood vessels for repair and regrowth of damaged tissue.
- Release of vascular endothelial growth factor (VEGF) stimulates cell proliferation and outgrowth of new capillaries in response to low oxygen levels.
Proliferation of Differentiated Cells: Liver Regeneration
- Liver cells are in G0.
- Removing a portion of the liver stimulates remaining cells to proliferate and regenerate the liver.
Proliferation of Differentiated Cells: Endothelial Cells
- Various cell types are capable of resuming cell proliferation.
- Smooth muscle cells make up the walls of large blood vessels.
- Some internal organs (e.g. liver) also have the capability to proliferate.
- Differentiated skeletal muscle and cardiac muscle cells are unable to divide.
Proliferation of Differentiated Cells
- Some differentiated cells retain the ability to divide and re-enter the cell cycle.
- Most differentiated cells are unable to divide.
- Less differentiated cells and self-renewing stem cells proliferate to replace cells.
Stem Cells
- Most fully differentiated cells are unable to divide (terminally differentiated).
- Stem cells replace cells though the proliferation of less differentiated self-renewing cells.
- Stem cells play a crucial role in the maintenance of most tissues and organs.
- Stem cells have the capacity to proliferate and replace differentiated cells throughout the lifetime of an animal.
- Key property of stem cells: one stem cell divides to produce one stem cell and one that divides and differentiates
Stem Cells
- Stem cells are self-renewing populations, acting as a source of differentiated cells throughout life.
- Stem cells play a critical role in tissues with short-lived cells, such as blood, skin, and the epithelial lining of the digestive tract.
Hematopoietic Stem Cells (HSCs)
- HSCs were first identified in 1961 by McCulloch and Till.
- HSCs are found in the blood-forming system and in the bone marrow of mice.
- HSCs proliferate and differentiate into multiple blood cells.
- A single HSC originates multiple blood cell types.
- HSCs are well characterised.
- All blood cells have limited life spans (less than a day to a few months).
- Over 100 billion blood cells are lost and replaced daily in humans.
Hematopoietic Stem Cells (HSCs)
- HSC descendants continue to proliferate.
- HSCs are committed to specific differentiation pathways.
- HSCs are influenced by factors and fully differentiated cells lose the capacity to proliferate.
Hematopoietic Stem Cells (HSCs)
- Early differentiation separates stem cells (e.g. myeloid and lymphatic).
- Multipotent stem cells divide to produce diverse stem cells.
Intestinal Stem Cells
- Intestinal stem cells are an example of self-renewal of epithelial tissue.
- The intestine is lined with a single layer of epithelial cells.
- Intestinal epithelial cells are exposed to harsh environments and only survive a few days before shedding into the digestive tract.
- Renewal of intestinal epithelium is a continual process throughout life.
- Stem cells (SCs) at the bottom of intestinal crypts produce new cells continuously.
- SCs give rise to transit-amplifying cells that divide rapidly.
- Transit-amplifying cells differentiate into various cell types.
- Each crypt has approximately six self-renewing SCs.
Skin Stem Cells
- Stem cells continuously renew skin and hair throughout life.
- Skin and hair are exposed to harsh environments, such as UV radiation.
- Each cell line is maintained by its own stem cells.
- The epidermis is a multilayered epithelium with a turnover every 2 weeks
- Epidermal stem cells in the single basal layer replace epidermal cells.
- Stem cells produce transit-amplifying cells, which divide and differentiate, forming the hair shaft.
- Sebaceous gland cells are derived from stem cells at the base of sebaceous glands.
Skeletal Muscle Stem Cells
- Skeletal muscle normally has low cell turnover.
- Skeletal muscle regenerates quickly in response to injury or exercise.
- Regeneration occurs from muscle stem cells (satellite cells).
- Satellite cells are located in the basal lamina of muscle fibers.
- Satellite cells are typically arrested in G0.
- Activated satellite cells proliferate in response to injury or exercise.
- Satellite cells produce progeny cells, divide several times, and differentiate/fuse to form new muscle fibers.
Medical Applications of Adult Stem Cells
- Ability to repair damaged tissue has potential clinical uses for replacing injured tissue and treating disorders.
- Established clinical applications like bone marrow transplantation that treat diabetes, muscular dystrophy, Parkinson's, and Alzheimer's disease.
Types of Stem Cells
- Adult stem cells: multipotent
- Embryonic stem cells: pluripotent
- Induced pluripotent stem cells (iPS cells): pluripotent
- Zygote stem cells: totipotent
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