Mesenchymal stem cell heterogeneity and ageing in vitro: A model approach

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 isolated 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.