17.04.2019Debora Kehl et al. in "Nature Regenerative Medicine"

Human mesenchymal stromal cells (hMSCs) are a heterogeneous population of non-clonal cells containing a multipotent stem cell fraction. More than 850 clinicals trials using hMSCs have been performed and these numbers are expected to continuously increase. This exemplifies the significance of hMSCs for future translational therapeutic approaches in the field of regenerative medicine.

Interestingly, it has become evident that functional benefits exerted by hMSCs upon transplantation are mainly due to secretome of the cells, influencing the microenvironment upon injury, promoting cytoprotection, angiogenesis, and tissue repair. For the treatment of ischemically damaged tissues, such as after myocardial infarction, the hMSC secretome has shown to reinstall perfusion via angiogenesis and thereby limiting tissue damage. In ischemic heart diseases, single cytokine therapy trials have not met expectations suggesting that the process of angiogenesis may need simultaneous orchestration of multiple factors at different concentrations to act synergistically – the concept of the hMSC secretome.

hMSC secretomes isolated from different tissue sources have shown dissimilarities with respect to their angiogenic potential. Although a plethora of studies have been published on this topic, a standardized comparative analysis on the angiogenic potential of hMSC secretomes from different human tissue sources has not been reported so far. Therefore, the study by Kehl et al. published in Nature Regenerative Medicine systematically compared the angiogenic potential of hMSC secretomes from the bone marrow (hBMSC), the umbilical cord Wharton’s jelly (hWJSC) and the adipose tissue (hADSC). This involved a proteomic analysis of the secretomes derived from 15 independent hMSC lines based on liquid chromatography tandem mass spectrometry. The results indicate a more complete angiogenic network with higher concentrations of angiogenesis related proteins in the secretomes of hWJSCs, followed by the secretomes of hBMSC. This proteomic data was confirmed with in vitro and in vivo functional assays, where both secretomes also showed a significant higher immune cell response and angiogenic potential compared to the secretomes of hADSC.

Overall these results suggest hWJSC secretome as the most potent hMSC source for inflammation-mediated angiogenesis induction. In the light of the increasing amount of studies focusing on the easily accessible hADSCs, this systematic analysis may initiate a scientific debate regarding the unequal biological response of hMSCs from different tissue sources. These differences may thus have significant implications on the selection of hMSCs for future clinical studies.

The full article, published at https://www.nature.com/articles/s41536-019-0070-y, was written by Debora Kehl as part of her PhD project with the contribution of Melanie Generali, Anna Mallone, Manfred Heller, Anne-Christine Uldry, Phil Cheng, Benjamin Gantenbein, Simon P. Hoerstrup and Benedikt Weber.