Elsevier

The Lancet

Volume 364, Issue 9429, 10–16 July 2004, Pages 193-199
The Lancet

Review
Adult stem cells—reprogramming neurological repair?

https://doi.org/10.1016/S0140-6736(04)16633-6Get rights and content

Summary

Much excitement has surrounded recent breakthroughs in embryonic stem-cell research. Of lower profile, but no less exciting, are the advances in the field of adult stem-cell research, and their implications for cell therapy. Clinical experience from use of adult haemopoietic stem cells in haematology will facilitate and hasten transition from laboratory to clinic—indeed, clinical trials using adult human stem cells are already in progress in some disease states, including myocardial ischaemia. Here, with particular reference to neurology, we review processes that might underlie apparent changes in adult cell phenotype. We discuss implications these processes might have for the development of new therapeutic strategies using adult stem cells.

Section snippets

Traditional stem-cell model

Pluripotent cells were first isolated from the embryonic inner cell mass.1 Ethical concerns, and the potential danger of teratoma formation, have contributed to the limited development of these cells as a therapeutic option: most scientists still talk in terms of “10–15 years”. However, adult stem cells have been used therapeutically for many years in malignant haematological disease and, more recently, for the treatment of inherited storage diseases. The haemopoietic stem cell has provided the

CNS stem cells

Neural stem cells have been identified in many species, including human beings.10, 11, 12, 13, 14 The discovery that progenitors attempt repair in human disease15, 16 has prompted the development of new theories to explain neurodegenerative disease,17 as well as offering hope that neurological repair could be enhanced via the supplementation, stimulation, or protection of endogenous precursors.18, 19 To detail the potential advantages of stem-cell therapy for particular neurological diseases is

Challenges to the hierarchical stem-cell model

Several findings challenge the traditional hierarchical model of tissue-specific adult stem cells.21, 22, 23 Bone-marrow-derived stem cells may have unexpected differentiation potential and can contribute to non-haemopoietic tissues. For example, donor-derived myocytes were found in mice after bone marrow transplantation;24 likewise, chimerism has been detected in the liver, brain, heart, and lungs of human recipients of bone-marrow transplants.25, 26, 27, 28, 29 Under conditions of strong

How adult stem cells might contribute to repair

At least six different mechanisms might be proposed: transdifferentiation, de-differentiation, transdetermination, cell fusion, true pluripotent stem-cell behaviour, and the production of trophic factors (figure 1). These mechanisms are, of course, not mutually exclusive.

Discussion

That cells previously thought to be of restricted lineage can give rise to progeny of different germ-cell lineages has questioned not only our understanding of stem-cell biology,115, 116, 117 but also wider issues pertaining to mechanisms of tissue homoeostasis and repair in the adult mammal.106 These issues have profound implications for reparative medicine.

To establish definitively the mechanism responsible for observed changes in cell phenotype, major technical difficulties must be overcome:

Search strategy and selection criteria

We searched MEDLINE with the search terms differentiation, fusion, transdifferentiation, and transdetermination. Only papers in the English language were reviewed. Additional papers were identified through searches of the authors' own files.

Conflict of interest statement

None declared.

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