Abstract

Mesenchymal stem cells (MSCs) stimulate angiogenesis within a wound environment and this effect is mediated through paracrine interactions with the endothelial cells present. Here we report that human MSC-conditioned medium (n=3 donors) significantly increased EaHy-926 endothelial cell adhesion and cell migration, but that this stimulatory effect was markedly donor-dependent. MALDI-TOF/TOF mass spectrometry demonstrated that whilst collagen type I and fibronectin were secreted by all of the MSC cultures, the small leucine rich proteoglycan, decorin was secreted only by the MSC culture that was least effective upon EaHy-926 cells. These individual extracellular matrix components were then tested as culture substrata. EaHy-926 cell adherence was greatest on fibronectin-coated surfaces with least adherence on decorin-coated surfaces. Scratch wound assays were used to examine cell migration. EaHy-926 cell scratch wound closure was quickest on substrates of fibronectin and slowest on decorin. However, EaHy-926 cell migration was stimulated by the addition of MSC-conditioned medium irrespective of the types of culture substrates. These data suggest that whilst the MSC secretome may generally be considered angiogenic, the composition of the secretome is variable and this variation probably contributes to donor-donor differences in activity. Hence, screening and optimizing MSC secretomes will improve the clinical effectiveness of pro-angiogenic MSC-based therapies.

Highlights

  • Many potential therapies for severe and/or chronic wounds fail as a result of poor vasculature[1]

  • This result was subject to a marked inter-donor variability, with conditioned media generated by both mesenchymal stem cells (MSCs)-1 and MSC-3 resulting in a significantly greater degree of EaHy-926 endothelial cell spreading than that generated by MSC-2 (Figure 2a, 2b)

  • EaHy-926 endothelial cell adherence on fibronectin coated plates was most advanced after two hours, compared to plates coated in either type I collagen or with decorin (Figure 3)

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Summary

Introduction

Many potential therapies for severe and/or chronic wounds fail as a result of poor vasculature[1]. Whilst the safety of MSC transplantation does not seem to be an issue[3, 4], the effectiveness of such treatment has exhibited considerable variability This variation in effect is problematic when translating preclinical research into MSC-based clinical therapy. Whilst there are reports that MSC are capable of endothelial differentiation[8,9], engraftment into new vasculature is low in vivo[10,11]. These and other studies have contributed to recent thought that the predominant regenerative activity of MSCs is due to their secretion of factors that stimulate endogenous cells at wound sites

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