Adult Stem Cells Stem Cells, Bone Marrow and Blood Potent Biology: Stem Cells, Cloning and Regeneration July 10-13, 2007

Stem Cells Embryonic – undifferentiated cells from the embryo that have the potential to become a wide variety of specialized cell types Zygote (totipotent) Morula (totipotent-pluripotent) Blastocyst (pluripotent) Inner Cell Mass (ICM) (pluripotent) Gastrula (multipotent)

Adult Stem Cells What are adult stem cells? Somatic cells that are unspecialized Depending on the tissue, the cells have different properties. What is the role of adult stem cells? Maintain and repair the bodies tissue Stem cells share 2 characteristics Proliferate - capable of long-term self-renewal Differentiate into mature cells Progenitor cells Precursor cells Adult stem cells are capable of self-renewal and give rise to daughter cells that are specialized to form the cell types found in the original body part.

Stem Cells Where are they found? Infants Adults Bone marrow (BM)

Bone Marrow, Stem Cells and Blood Hiroshima and Nagasaki 1943 Radiation Compromised hematopoietic system Couldn’t produce white blood cells (WBC’s) Couldn’t produce platelets Mouse studies Irradiation to whole body resulted in death of the mice BM cells from normal mouse injected into lethally irradiated mice Prevented death from bone marrow failure McColloch and Till; Radiation Research 13, 115-125; 1960

Why Did This Bone Marrow Transplant Work? Bone Marrow is the site of blood cell (red blood cells, white blood cells, and platelets) production… Hematopoiesis.

Hematopoiesis: Stem Cell Hierarchy Process begins with Hematopoietic Stem Cells (HSCs) capable of Proliferation Differentiation Differentiation of HSCs follows 2 cell lines. Myeloid Lymphoid Hematopoietic Stem Cell

Hematopoiesis: Stem Cell Hierarchy Cells in either line differentiate along an irreversible succession or hierarchy of precursor cells Each descendent cell has progressively limited potential.

Hematopoiesis: Stem Cell Hierarchy How do HSC’s know which pathway to follow or which cell to become? Differentiation is directed by signal molecules (growth factors known as cytokines and interleukins) Bone marrow stromal cells are the major source of these growth factors. Bm CONTains 3 sc POPULATions HSCs, StROMAL CELLS, AND ENDOThelial progenitOR CELLS

Hematopoiesis: Stem Cell Hierarchy Cytokines are a family of proteins that direct differentiation of a particular lineage. Combinations of cytokines can stimulate Proliferation and/or Differentiation

Hematopoiesis: Stem Cell Hierarchy http://www.biocarta.com/pathfiles/h_stemPathway.asp

Summary The development of different blood cell types from bone marrow stem cells is an example of how the body uses adult stem cells. Different types of blood cells (RBC, WBC, platelets) have very different functions. All types of human blood cells differentiate from bone marrow stem cells. The differentiation of human blood cells is hierarchical and irreversible. An early division in the differentiation of human blood cells is along two (myeloid and lymphoid) precursor stem cell lines. Differentiation is directed by signaling molecules The signaling molecule(s) to which a stem cell is exposed determines which blood cell it becomes.