Biomedical Engineering Reference
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Mesenchymal Stem Cell Heterogeneity
and Ageing In Vitro: A Model Approach
Jörg Galle, Martin Hoffmann and Axel Krinner
Abstract Mesenchymal Stem Cell (MSC)-based therapies have been suggested as
a particular promising strategy in tissue regeneration. These cells can easily be
obtained from the patient and are able to produce a large number of progeny that
can be induced to form connective tissue. However, rapid amplification of the
isolated cells is required for their therapeutic application. While already the iso-
lated populations are heterogeneous regarding various functional and molecular
aspects, this heterogeneity further evolves during amplification. Understanding the
origin and development of MSC heterogeneity will help to improve MSC culture
conditions and thus facilitate their clinical use. We here review recent results on
MSC heterogeneity and introduce a mathematical framework that approaches
MSC heterogeneity on the single cell level. This approach bases on the concept of
noise-driven MSC differentiation and allows describing MSC heterogeneity with
respect to their differentiation state and age. It is capable of describing the impact
of MSC heterogeneity on in vitro expansion and differentiation. We present new
results on the formation of an age structure in MSC populations in vitro and the
age-dependent differentiation structure of MSC populations. Moreover, we discuss
open questions regarding MSC adaptation to changing environments and the cell
intrinsic control of state fluctuations.
J. Galle ( & ) A. Krinner
Interdisciplinary Centre for Bioinformatics (IZBI),
University of Leipzig, Leipzig, Germany
e-mail: galle@izbi.uni-leipzig.de
M. Hoffmann
Biomathematics and Bioinformatics Group,
Department of Knowledge Engineering,
Maastricht University, Maastricht, The Netherlands
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