Heterogeneity of proangiogenic features in mesenchymal stem cells derived from bone marrow, adipose tissue, umbilical cord, and placenta

Abstract

BackgroundMesenchymal stem cells (MSCs) have been widely proven effective for therapeutic angiogenesis in ischemia animal models as well as clinical vascular diseases. Because of the invasive method, limited resources, and aging problems of adult tissue-derived MSCs, more perinatal tissue-derived MSCs have been isolated and studied as promising substitutable MSCs for cell transplantation. However, fewer studies have comparatively studied the angiogenic efficacy of MSCs derived from different tissues sources. Here, we evaluated whether the in-situ environment would affect the angiogenic potential of MSCs.MethodsWe harvested MSCs from adult bone marrow (BMSCs), adipose tissue (AMSCs), perinatal umbilical cord (UMSCs), and placental chorionic villi (PMSCs), and studied their “MSC identity” by flow cytometry and in-vitro trilineage differentiation assay. Then we comparatively studied their endothelial differentiation capabilities and paracrine actions side by side in vitro.ResultsOur data showed that UMSCs and PMSCs fitted well with the minimum standard of MSCs as well as BMSCs and AMSCs. Interestingly, we found that MSCs regardless of their tissue origins could develop similar endothelial-relevant functions in vitro, including producing eNOS and uptaking ac-LDL during endothelial differentiation in spite of their feeble expression of endothelial-related genes and proteins. Additionally, we surprisingly found that BMSCs and PMSCs could directly form tubular structures in vitro on Matrigel and their conditioned medium showed significant proangiogenic bioactivities on endothelial cells in vitro compared with those of AMSCs and UMSCs. Besides, several angiogenic genes were upregulated in BMSCs and PMSCs in comparison with AMSCs and UMSCs. Moreover, enzyme-linked immunosorbent assay further confirmed that BMSCs secreted much more VEGF, and PMSCs secreted much more HGF and PGE2.ConclusionsOur study demonstrated the heterogeneous proangiogenic properties of MSCs derived from different tissue origins, and the in vivo isolated environment might contribute to these differences. Our study suggested that MSCs derived from bone marrow and placental chorionic villi might be preferred in clinical application for therapeutic angiogenesis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0418-9) contains supplementary material, which is available to authorized users.

Aldehyde dehydrogenase activity of Wharton jelly mesenchymal stromal cells: isolation and characterization

“…MSCs have been widely proven effective for therapeutic angiogenesis in ischemia animal models as well as clinical vascular diseases. However, heterogeneous proangiogenic properties of MSCs derived from different tissue origins have been described and these differences are likely linked to the environment (Du et al 2016b). In this study, we observed an increased expression for angiogenic genes ANG1, ANG2, FLT1 and VEGF in ALDH ?…”

Harnessing mesenchymal stem cell secretome: Effect of extracellular matrices on proangiogenic signaling

“…Further our study also revealed that the modulation of secretory profiles translated to enhanced sprouting assessed via rECM gelbased angiogenesis assay. Heterogeneous proangiogenic properties of MSCs as a function of tissue origins have been previously reported (Amable, Teixeira, Carias, Granjeiro, & Borojevic, 2014;Du et al, 2016;Hsieh et al, 2013). Studies have demonstrated that MSCs derived from bone marrow and placental chorionic villi exhibited significant therapeutic angiogenic activities compared with those harvested from adipose tissue or umbilical cord (Du et al, 2016).…”

“…Heterogeneous proangiogenic properties of MSCs as a function of tissue origins have been previously reported (Amable, Teixeira, Carias, Granjeiro, & Borojevic, 2014;Du et al, 2016;Hsieh et al, 2013). Studies have demonstrated that MSCs derived from bone marrow and placental chorionic villi exhibited significant therapeutic angiogenic activities compared with those harvested from adipose tissue or umbilical cord (Du et al, 2016). On the other hand, studies have also reported that adipose tissue as well as umbilical cord-derived MSCs exhibit better proangiogenic profile than bone marrow-derived MSCs (Amable et al, 2014;Hsieh et al, 2013).…”

Endogenous biological factors modulated by substrate stiffness regulate endothelial differentiation of mesenchymal stem cells

“…For example, Oswald et al differentiated MSCs into ELCs using vascular endothelial growth factor (VEGF), and the ELCs expressed endothelial‐specific markers, kinase insert domain receptor ( KDR ) and von Willebrand factor ( vWF ). In another study by Du et al, human MSCs during endothelial differentiation induced by VEGF showed endothelial cell phenotypes in culture. In addition to soluble growth factors, complete endothelial differentiation of stem cells requires signaling cues from the extracellular matrix (ECM) .…”