1. Stem Cells and the Maintenance of Adult Tissues
Chapt Stem cells have great potential
Adult stem cells
Embryonic stem cells
In early development, cells proliferate rapidly, then differentiate to form specialized cells of adult tissues
Most differentiated cells in adult animals are no longer capable of proliferation.
If cells are lost, replace by proliferation of cells derived from self-renewing stem cells.

2. Stem Cells,Maintenance of Adult Tissues
1. Some differentiated cells can
proliferate to repair damaged tissues
Fibroblasts in connective tissue
proliferate in response to platelet-derived
growth factor (PDGF) released at wound
Endothelial cells lining blood vessels
proliferate to form new blood vessels
(repair and regrowth of damaged tissue)
Triggered by vascular endothelial growth
factor (VEGF), from cells that lack oxygen
Fig ,14, 15

3. Stem Cells and the Maintenance of Adult Tissues
2. Adult Stem cells:
Less differentiated, self-renewing cells in most adult tissues.
Retain capacity to proliferate, replace differentiated cells throughout lifetime of animal.
** Divide to produce one daughter cell that remains stem cell and one that divides, differentiates
Ex. blood cells, sperm,
epithelial cells skin, intestine
Fig

4. specialized functions
Fig Formation of blood cells
Hematopoietic (blood-forming) stem cells were the first identified (1961):
distinct types
specialized functions
Short life span
from bone marrow

5. Stem Cells and Maintenance of Adult Tissues
Epithelial cells that line intestines live only a few days before they die
Fig

6. Stem Cells and the Maintenance of Adult Tissues
Adult stem cells potential utility in medicine.
Hematopoietic stem cell transplantation
(or bone marrow transplantation)
important role in treatment of cancers.
Fig
Cord blood is source of hematopoietic stem cells
Epithelial stem cells - skin grafts for burns, wounds, and ulcers.

7. Embryonic Stem Cells and Therapeutic Cloning
Embryonic stem cells (ES)
Grow indefinitely as pure stem cell populations
Pluripotency — capacity to develop into all of different types of cells in adult tissues.
Enormous interest -
basic science and clinical applications.
Distinction cloning cells versus cloning organisms

8. Embryonic Stem Cells and Therapeutic Cloning
ES cells first cultured from mouse embryos in 1981.
Mouse ES cells important experimental tool:
Can introduce altered genes into mice.
Model system to study molecular basis of cell differentiation
Fig ES cells can differentiate:
Martin Expt: neuron-like, endodermal, cartilage

9. Embryonic Stem Cells and Therapeutic Cloning
Mouse ES cells need growth factor LIF, to maintain undifferentiated state (leukemia inhibitory factor)
LIF signals through JAK/STAT path
If LIF is removed, cells
aggregate and differentiate.
Different growth factors direct
differentiation along specific paths
Model for future human therapeutics:
Diseases like Parkinson’s, diabetes
Human ES cell lines exist
Fig

10. Embryonic Stem Cells and Therapeutic Cloning
1997 Dolly the sheep cloned:
Somatic cell nuclear transfer process
This cloning in mammals is difficult and inefficient
Possible therapeutic cloning
Fig

11. Embryonic Stem Cells and Therapeutic Cloning
Nucleus from adult human cell transferred to enucleated egg
Resulting embryo cells used to produce differentiated cells for transplantation therapy.
Bypasses problem of tissue rejection
Problems with therapeutic cloning:
Low efficiency of generating embryos by somatic cell nuclear transfer.
Ethical concerns:
Possible cloning of humans (reproductive cloning),
destruction of embryos
Fig therapeutic cloning for personalized tissue transplants

12. Embryonic Stem Cells and Therapeutic Cloning
Induced pluripotent stem cells:
Very recent procedures
may overcome technical,
ethical difficulties
Reprogram somatic cells to
resemble embryonic stem cells.
Only 4 key transcription factors
reprogram adult mouse somatic cells
Oct4, Sox2, Klf4, c-Myc)
Also adult human fibroblasts
Fig