Abstract

Mesenchymal stem cells (MSCs) are somatic cells with a dual capacity for self-renewal and differentiation, and diverse therapeutic applicability, both experimentally and in the clinic. These cells can be isolated from various human tissues that may differ anatomically or developmentally with relative ease. Heterogeneity due to biological origin or in vitro manipulation is, nevertheless, considerable and may equate to differences in qualitative and quantitative characteristics which can prove crucial for successful therapeutic use. With this in mind, in the present study we have evaluated the proliferation kinetics and phenotypic characteristics of MSCs derived from two abundant sources, that is, fetal umbilical cord matrix (Wharton's jelly) and adult adipose tissue (termed WJSC and ADSC, resp.) during prolonged in vitro expansion, a process necessary for obtaining cell numbers sufficient for clinical application. Our results show that WJSC are derived with relatively high efficiency and bear a substantially increased proliferation capacity whilst largely sustaining the expression of typical immunophenotypic markers, whereas ADSC exhibit a reduced proliferation potential showing typical signs of senescence at an early stage. By combining kinetic with phenotypic data we identify culture thresholds up to which both cell types maintain their stem properties, and we discuss the practical implications of their differences.

Highlights

  • Mesenchymal stem cells (MSCs) are somatic cells with an ability to self-renew and to differentiate towards a variety of specialized cell types through a combination of symmetric and asymmetric divisions

  • In the case of MSCs-based cytotherapy, it is estimated that approximately 1–5 million cells/kg body are required for successful outcome; a degree of ex vivo expansion is necessary, and this holds true in over 60% of cases of cellular transplants [12, 13]

  • A question arises whether MSCs can sustain their expansion potential and phenotypic stability over prolonged culture periods, for how long, and whether possible disparities exist between diverse populations, rendering some of them more competent and suitable for consideration in cytotherapy protocols

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Summary

Introduction

Mesenchymal stem cells (MSCs) are somatic cells with an ability to self-renew and to differentiate towards a variety of specialized cell types through a combination of symmetric and asymmetric divisions. Populations of MSCs can be relatively isolated from a number of tissues that may differ both developmentally (e.g., fetal versus adult) and anatomically (e.g., bone marrow versus fat). Due to their unique properties of self-renewal and multipotency, as well as their immunogenic profile [1,2,3] (in many cases they have been shown to be hypoimmunogenic and/or can be transplanted autologously following ex vivo expansion), they have been utilized in several therapeutic applications such as tissue repair and regeneration and autoimmune disease over the last decade [4]. A question arises whether MSCs can sustain their expansion potential and phenotypic stability over prolonged culture periods, for how long, and whether possible disparities exist between diverse populations, rendering some of them more competent and suitable for consideration in cytotherapy protocols

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