The Cell, 5e

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Stem Cells
General Concepts
By Syed Tahir Abbas Shah
Outline

Introduction

History

Types of Stem Cells

Regulation of Stem Cells

Application of Stem Cells

Ethical Issues

Conclusion
Introduction-Definition
Stem cells— Cells with the ability to divide
for indefinite periods in culture and to give
rise to specialized cells.
Introduction-Properties

Capable of dividing
and renewing
themselves for long
periods

Unspecialized

Can give rise to
specialized cell types
Introduction-Stem cell strategies
Formation of blood cells from Stem Cell
Stem Cell Research History
1956-First successful bone marrow
transplant between relatives is completed
1968-In vitro fertilization begins
1973-First bone marrow transplant between
unrelated people is successful
1978-Blood (adult) stem cells are discovered in
umbilical cord blood
1981-Mouse embryonic stem cells are first
isolated
http://www.stemcellresearchformichigan.com/faq-history.php
Stem Cell Research History
1995-University of Wisconsin
isolates embryonic stem cells in primates
1998-University of Wisconsin researchers, led
by Dr. James Thomson, isolate first
human embryonic stem cells
2002-Pancreatic cells derived from
mouse embryonic stem cells cure diabetes in
mice
http://www.stemcellresearchformichigan.com/faq-history.php
Stem Cell Research History
2004-South Korean researchers claim to
have cloned human embryo. Research is later
discredited as untrue.

Nerve cells lost in Parkinson’s disease are
produced from human embryonic stem cells

California becomes first state to provide own
funding for embryonic stem cell research
2005-Human neural cells injected into mice help
reverse paralysis
http://www.stemcellresearchformichigan.com/faq-history.php
Stem Cell Research History
2006-Embryonic stem cells first grown without
animal products in the feeder layer of the
culture
2007-Teams of researchers in Wisconsin and
Japan modify adult skin cells into induced
Pluripotent Stem (iPS) cells which behave
like embryonic stem cells by using viruses to
introduce four genetic factors that cause the
change
http://www.stemcellresearchformichigan.com/faq-history.php
Stem Cell Research History
2008-Various researchers announce success
with creating iPS cells using fewer viruses and
genes
2009-FDA approves world's first clinical trial
using human embryonic stem cell-based
therapies for California company to test a
treatment for spinal cord injury

NIH guidelines
http://www.stemcellresearchformichigan.com/faq-history.php
Stem Cell Types (Sources)

Embryonic Stem Cells

Fetal Stem Cells

Adult Stem Cells

Amniotic Stem Cells

Induced pluripotent Stem Cells
Embryonic vs Adult Stem Cells
Induced Pluripotent Stem Cells
Stem Cell Types (Potency)
Totipotent(omnipotent)- can differentiate into embryonic and
extraembryonic cell types
Pluripotent- can differentiate into nearly all cells i.e. cells
derived from any of the three germ layers.
Multipotent- can differentiate into a number of cells, but only
those of a closely related family of cells.
Oligopotent- stem cells can differentiate into only a few cells,
such as lymphoid or myeloid stem cells.
Unipotent- cells can produce only one cell type, their own, but
have the property of self-renewal (e.g. muscle stem cells)
Origin of Human Pluripotent Cells
Stem Cell Types (Potency/Source)
Stem Cell Regulation- Niche
Stem Cell Regulation- Niche
Stem Cell Regulation- Epigenetic
Regulation of long-term self renewal
Mouse ESCs
LIF (Smith et al., Nature, 1988)
BMP (or serum) (Ying et al, Cell, 2003)
3i (Ying et al, Nature, 2008)
(Buehr et al, Cell, 2008)
LIF and BMP act on downstream differentiation
signals of MAPK
He S et al. 2009. Annu Rev Cell Dev Biol;
Dr. Fei Wang
Stem Cell Regulation- MicroRNAs
Cancer Stem Cells
Application of Stem Cells
Differentiation of embryonic stem cells
Strategies to repair heart muscle with adult stem cells
Embryonic Stem Cells and Therapeutic Cloning

In therapeutic cloning, a nucleus from
an adult human cell would be
transferred to an enucleated egg.

The resulting embryo could produce
differentiated cells for transplantation
therapy.

This would bypass the problem of
tissue rejection.
Embryonic Stem Cells and Therapeutic Cloning
Ethical Issues
Summary

Properties- Self renewal, unspecialized,
give rise to specialized cells.

Types- Totipotent, pluripotent, unipotent

Regulation- Niche, miRNA, epigenetic

Application- Therapeutic cloning, treatment
of a variety of diseases.

Ethical Issues- Donation of biological
material, hESC, Clinical Trails
References
Donovan, P. J., & Gearhart, J. (2001). The end of the beginning for pluripotent
stem cells. Nature, 414(6859), 92-97. doi:10.1038/35102154
Engler, A. J., Sen, S., Sweeney, H. L., & Discher, D. E. (2006). Matrix elasticity
directs stem cell lineage
specification. Cell, 126(4), 677-689.
doi:10.1016/j.cell.2006.06.044
Jones, D. L., & Wagers, A. J. (2008). No place like home: Anatomy and function
of the stem cell niche. Nature Reviews.Molecular Cell Biology, 9(1), 11-21.
doi:10.1038/nrm2319
Gangaraju, V. K., & Lin, H. (2009). MicroRNAs: Key regulators of stem
cells. Nature Reviews.Molecular
Cell Biology, 10(2), 116-125.
doi:10.1038/nrm2621
http://www.stemcellresearchformichigan.com/faq-history.php
http://stemcells.nih.gov/info/
http://en.wikipedia.org/wiki/File:Stem_cell_treatments.svg
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