Elsevier

Blood Reviews

Volume 19, Issue 1, January 2005, Pages 29-38
Blood Reviews

REVIEW
Stem cell plasticity

https://doi.org/10.1016/j.blre.2004.03.001Get rights and content

Abstract

The central dogma in stem cell biology has been that cells isolated from a particular tissue can renew and differentiate into lineages of the tissue it resides in. Several studies have challenged this idea by demonstrating that tissue specific cell have considerable plasticity and can cross-lineage restriction boundary and give rise to cell types of other lineages. However, the lack of a clear definition for plasticity has led to confusion with several reports failing to demonstrate that a single cell can indeed differentiate into multiple lineages at significant levels. Further, differences between results obtained in different labs has cast doubt on some results and several studies still await independent confirmation. In this review, we critically evaluate studies that report stem cell plasticity using three rigid criteria to define stem cell plasticity; differentiation of a single cell into multiple cell lineages, functionality of differentiated cells in vitro and in vivo, robust and persistent engraft of transplanted cells.

Introduction

A stem cell is defined by three main criteria: self-renewal, ability to differentiate into multiple cell types, and ability of in vivo reconstitution of a given tissue. A fertilized egg is capable of not only forming cells of the mesoderm, endoderm and ectoderm layer, and germ cells, but also the supporting trophoblast required for the survival of the developing embryo. These cells are therefore at the top of the hierarchy of stem cells and termed `totipotent'. Embryonic stem (ES) cells and embryonic germ (EG) cells, isolated from the inner cell mass of the blastocyst or from primordial germ cells of an early embryo, give rise to mesoderm, endoderm, ectoderm and germ cells but not extra-embryonic tissues, and are therefore termed `pluripotent'. Stem cells isolated from various adult organs self-renew and differentiate into multiple organ specific cell types are termed `multipotent stem cells'. Committed cells that have limited or no self-renewal ability and differentiate into only one defined cell type are termed `progenitor cells' or `precursor cells'.

Section snippets

Adult stem cells and plasticity

Traditionally, adult stem cells have been viewed as committed to a particular cell fate to produce cells from the tissue of origin but not cells of non-related tissues. For example, neural stem cells (NSCs) give rise to the three main types of nerve cells present in adult brain, hematopoietic stem cells (HSCs) produce blood, etc. Various reports over the last six years challenge this central dogma by demonstrating that adult stem cells, under certain microenvironmental conditions, give rise to

Mechanisms of stem cell plasticity

What mechanism underlies the apparent greater potency of adult stem cells, termed plasticity, is the subject of ongoing and very lively debates in the scientific community. Several possible mechanisms may underlie the apparent plasticity.

The most obvious explanation might be that, as a number of the reports were based on infusion of non-purified populations of cells, co-infusion of multiple different stem cells accounts for the engraftment in multiple tissues. Indeed, skeletal muscle contains

Conclusion

Irrespective of the mechanism underlying stem cell plasticity, many believe that adult stem cells hold considerable clinical potential. Some of the potentials and challenges of adult stem cell use in therapy are outlines in box 2.

Potential of adult stem cells

  • treatment of degenerative disorders of many organs

  • allows autologous transplantation thereby reducing immune rejection

  • ex vivo gene correction of autologous stem cells in case of genetic disorders

Challenges to overcome

  • confirm greater

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