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

2. 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)

3. 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.

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

5. 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, ; 1960

6. 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.

7. 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

8. 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.

9. 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

10. 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

11. Hematopoiesis: Stem Cell Hierarchy

12. 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.