Stem Cell Biology PDF

Stem Cell Biology Cell Biology MED105 Prof A. Stephanou  Objectives: Understand the different type of stem cells and their characteristic's How stem cells are derived Problems associated with Stem cell therapy Stem cells for treatment of cardiac hematopoietic & diabetic disea...

Stem Cell Biology Cell Biology MED105 Prof A. Stephanou  Objectives: Understand the different type of stem cells and their characteristic's How stem cells are derived Problems associated with Stem cell therapy Stem cells for treatment of cardiac hematopoietic & diabetic diseases.  Stem Cell History 1998 - Researchers first extract stem cells from human embryos 1999 - First Successful human transplant of insulin- making cells 2002 - Juvenile Diabetes Research Foundation International creates $20 million fund-raising effort to support stem-cell research 2004 - Harvard researchers grow stem cells from embryos using private funding Stem cell scientists share 2012 Nobel Prize for medicine: Sir John Gurdon, UK and Shinya Yamanaka (Japan)  Stem Cell – Definition ⚫ A cell that has the ability to continuously divide and differentiate (develop) into various other kind(s) of cells/tissues 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)  Kinds of Stem Cells Stem cell type Description Examples Cells from early Each cell can develop Totipotent (1-3 days) into a new individual embryos Some cells of Cells can form any (over Pluripotent blastocyst (5 to 14 200) cell types days) Cells differentiated, but Fetal tissue, cord Multipotent can form a number of blood, and adult other tissues stem cells  This cell Can form the Embryo and placenta This cell Can just form the embryo Fully mature  Kinds of Stem Cells Embryonic stem cells five to six-day-old embryo Embryonic germ cells derived from the part of a human embryo or fetus. Adult stem cells undifferentiated cells found among specialized or differentiated cells in a tissue or organ after birth  Multipotent stem cells ⚫ Multipotent stem cells – limited in what the cells can become Blastocyst  Adult Stem Cells Skin Fat Cells Bone marrow Brain Many other organs & tissues  Bone Marrow ⚫ Found in spongy bone where blood cells form ⚫ Used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. ⚫ treat patients diagnosed with leukemia, aplastic anemia, and lymphomas ⚫ Need a greater histological immuno-compatibility  Blood Cell Formation Hemangioblasts are the multipotent precursor cells that can differentiate into hematopoietic cells Hemangioblasts  Hemangioblasts The overall scheme for hematopoiesis The embryonic stem cell, the hemangioblast, gives rise to angioblasts that make both vessels and universal blood stem cells. The universal stem cells renew and also form the myeloid and lymphoid precursors. Precursor stem cells for muscle Mesoangioblasts can differentiate in distinct lineages in the muscle. Satellite cells are precursors to skeletal muscle cells and are responsible for the ability of muscle tissue to regenerate  Genetic control of muscle cell differentiation Myo D is a master regulator of muscle cell differentiation from myogenic precursor cells (Myogenin, Myf-5, and MRF-4). These are transcription factors (basic helix-loop-helix) and activate genes that are needed for muscle cell differentiation.  Stem Cell Applications Tissue repair - nerve, heart, muscle, organ, skin Cancers Autoimmune diseases - diabetes, rheumatoid arthritis, MS  Medical importance The ability of stem cells to multiply and produce a wide range of differentiated cell types is potentially of great medical importance. When signals that direct stem cell differentiation become better understood, it may be possible to use the cells to replace damaged or diseased tissue. Examples include Alzheimer’s disease, Parkinson’s disease, loss of brain tissue after stroke or injury, inducing b cells to treat diabetes, and restoring cartilage that is damaged by arthritis. Human embryonic stem cells are particularly interesting. They are found in the inner cell mass of the early blastula. They divide infinitely and produce many types of differentiated cells. In the future, it may be possible to clone the cell of a patient who has suffered a heart attack. This could be used to create a blastocyst by nuclear transfer to an oocyte. Stem cells from the inner cell mass could be harvested and induced to form cardiac muscle. These could be transplanted into the patient’s heart muscle to repopulate the scar. Currently, research with embryonic stem cells is not funded by the US government, and political issues prevent rapid progress in this area by US scientists.  New research – Reprogramming Cells  Challenges to Stem Cell/Cloning Research ◼ Stem cell development or proliferation must be controlled once placed into patients. ◼ Possibility of rejection of stem cell transplants as foreign tissues is very high. ◼ Contamination by viruses, bacteria, fungi, and Mycoplasma possible.  Technical Challenges ⚫ Source - Cell lines may have mutations. ⚫ Delivery to target areas ⚫ Prevention of rejection ⚫ Suppressing tumors Problems with Adult Stem Cells Mutations can lead to leukemia  Why is Stem Cell Research So Important to All of Us? ◆ Stem cells can replace diseased or damaged cells ◆ Stem cells allow us to study development and genetics ◆ Stem cells can be used to test different substances (drugs and chemicals) Mechanism of Cardiac Diseases and Cardiac Stem Cell Therapy Tissue Regeneration  Cardiac Regeneration ⚫ Cardiomyocytes initiate DNA synthesis and re-enter the cell cycle- division of existing cardiomyocytes ? ⚫ Dedifferentiation of cardiomyocytes near the injured zone occurs before their proliferation and loss of expression of cardiac contractile proteins (a-MHC). ⚫ Initiated predominantly by undifferentiated stem or progenitor cells from the heart. ⚫ In fact, in mammalian hearts, cardiomyocytes bordering a myocardial infarction rarely divide after injury. Cardiac Regeneration Stem cells Used for cardiac repair  Cardiac Tissue Engineering Adult heart, like the brain, is mainly composed of terminally differentiated cells, but is not a terminally differentiated organ because it contains stem cells supporting its regeneration. The existence of these cells opens new opportunities for myocardial repair Yaakov Nahmias created the first heart model grown from stem cells with all the key structures, including ventricles, atria, an epicardium (outer shell), endocardium (inner lining), and natural pacemakers. Clinical Trials of Hematopoietic Cell Transplantation  Stem Cells and Diabetes ◼ b cells are not generated from adult stem cells in the pancreas. ◼ It is unlikely that a cure for diabetes will come from adult stem cells. ◼ Embryonic stem cells have been shown to generate insulin-producing b cells. Germ Layer Differentiation  Forming Specialized Cells (Inner Cell Mass) ◼ Growth factors and other signals tell a stem cell when to differentiate and what type of cell to become. ◼ The same growth factors and signals could be used to direct the differentiation of human embryonic stem cells grown in culture.  Early endoderm cells receive specific signals at critical times. Signals include transcription factors, cytoplasmic factors, and growth factors. Signals also include physical contact with other cells. The specific combination and timing of signals direct which cell types these cells will differentiate to form. Thus, the first pancreatic bud cells form. Some of these cells form the endocrine pancreas. By following the normal progression of events, researchers know that signals from adjacent blood vessels are needed for β cells to differentiate from those of the endocrine pancreas. If there is not direct contact between future β cells and blood vessels, β cells will not form.  The Future Task: ◼ Guiding cultured embryonic stem cells to become insulin-producing b cells.  Cancer Stem Cells Normal stem cells Rare cells within organs with the ability to self- renew and give rise to all types of cells within the organ to drive organogenesis Cancer stem cells Rare cells within tumors with the ability to self- renew and give rise to the phenotypically diverse tumor cell population to drive tumorigenesis  Cancer Stem Cell Therapy Cancer stem cells have been discovered in breast, prostate, skin, blood, brain and other tumors. Cancer stem cells are capable of persistent self renewal and differentiating into other cells of limited proliferation potential in the tumor. Recent evidence suggests that specific subsets of genes are abnormally expressed in cancer stem cells. Aim of cancer stem cell therapy is to kill, stop the proliferation of, or cause differentiation of cancer stem cells. Therapeutic implications of Cancer Stem Cells Most therapies fail to consider the difference in drug sensitivities of cancer stem cells compared to their non-tumorigenic progeny. Most therapies target rapidly proliferating non-tumorigenic cells and spare the relatively quiescent cancer stem cells. Summary of stem cell source Summary of stem cell source