Elsevier

Experimental Gerontology

Volume 40, Issue 12, December 2005, Pages 926-930
Experimental Gerontology

Mini Review
Mesenchymal stem cell aging

https://doi.org/10.1016/j.exger.2005.07.006Get rights and content

Abstract

Stem cells are located throughout the adult body of higher organisms, supporting a continuous renewal and repair of tissues. Unique abilities of stem cells are self-renewal and multipotential differentiation. It is, therefore, of critical importance for an organism to maintain and control quantity and quality of stem cells within a given pool. Otherwise, when something goes awry within a stem cell, it is likely to have far-reaching effects.

Mesenchymal stem cells (MSC) derived from various sources such as bone marrow or fat have been expanded in culture and differentiated in vitro into several lineages such as adipocytes, osteocytes or chondrocytes. In particular, aged human MSC show a decline in differentiation potential as well as in proliferation rate. The latter most likely reflects the fact that aged MSC suffer from eroded telomeres. Besides the individual age of the cell, stem and progenitor cell functions are influenced by the cellular environment, i.e. the niche and the architecture of the tissue, they reside in. This contribution reviews current knowledge about MSC aging (in vitro or in vivo), and respective difficulties for tissue engineering and stem cell therapy.

Introduction

It is commonly believed that stem and precursor cells are involved in continuous maintenance and repair of most tissue types. Taken into consideration that stem cells are capable of self-renewal and that they share the ability to differentiate in multiple lineages, this class of cells is of paramount importance for an organism, not only during development, but also during adulthood with respect to cellular homeostasis. In contrast to higher animals, the life span of microorganisms as well as simple multi-cellular animals is believed to correspond to cellular longevity. As long as damaged cells within a specialized organ are replaced, proper physiological function will be maintained which would contribute to longevity of the whole organism (Van Zant, 2003, Young et al., 2004). Consequently, stem cells must have life spans that may be equal to that of the organism they reside in (Van Zant and Liang, 2003). Therefore, they have to face long replicative histories and thus accumulate genetic damage. In addition to this, they are certainly subject to damage from intracellular and extracellular sources such as reactive oxygen species (Hasty et al., 2003).

Section snippets

Properties of mesenchymal stem cells

Stem cells for non-haematopoietic tissues, which can be derived from bone marrow are commonly termed mesenchymal stem cells (MSC). This definition (first coined by Arnold Caplan, 1991) and many other terms (marrow stromal cells, precursors of non-haematopoietic tissue, colony forming unit fibroblasts or multipotent adult progenitor cells) have been introduced in the field and refer to differences of isolation and cultivation or epitope characterization. The basal term ‘mesenchyme’ was first

Senescence of mesenchymal stem cells

MSC in culture show replicative senescence phenotypes depending on the species they have been derived from. For instance, human MSC cease growth rather early (around 40–50 population doublings) (Stenderup et al., 2003), whereas murine MSC can be passaged for more than hundred population doublings (Meirelles Lda and Nardi, 2003). In vitro senescence of MSC is paralleled by a progressive loss of clonal multipotentiality. By and large, this supports a hierarchical model, with a pathway of

Acknowledgements

GL is an APART fellow of the Austrian Academy of Sciences. He is further supported by the Jubilee Fund of the Austrian National Bank, project 10481 and by the Austrian Science Fund (FWF), project S9309-B09.

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