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

1956-First successful bone marrow transplant between relatives is completed 1968-In vitro fertilization begins First bone marrow transplant between unrelated people is successful Blood (adult) stem cells are discovered in umbilical cord blood Mouse embryonic stem cells are first isolated 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 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 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 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 Stem Cell Research History

 Embryonic Stem Cells  Fetal Stem Cells  Adult Stem Cells  Amniotic Stem Cells  Induced pluripotent Stem Cells Stem Cell Types (Sources)

Embryonic vs Adult Stem Cells

Induced Pluripotent Stem Cells

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) Stem Cell Types (Potency)

Origin of Human Pluripotent Cells

Stem Cell Types (Potency/Source)

Stem Cell Regulation- Niche

Stem Cell Regulation- Epigenetic

He S et al Annu Rev Cell Dev Biol; Mouse ESCs LIF (Smith et al., Nature, 1988) BMP (or serum) (Ying et al, Cell, 2003) 3i (Ying et al, Nature, 2008) LIF and BMP act on downstream differentiation signals of MAPK (Buehr et al, Cell, 2008) Regulation of long-term self renewal 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

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