Conditioned Medium From Human Amniotic Mesenchymal Stromal Cells Limits Infarct Size and Enhances Angiogenesis

Abstract

The paracrine properties of human amniotic membrane-derived mesenchymal stromal cells (hAMCs) have not been fully elucidated. The goal of the present study was to elucidate whether hAMCs can exert beneficial paracrine effects on infarcted rat hearts, in particular through cardioprotection and angiogenesis. Moreover, we aimed to identify the putative active paracrine mediators. hAMCs were isolated, expanded, and characterized. In vitro, conditioned medium from hAMC (hAMC-CM) exhibited cytoprotective and proangiogenic properties. In vivo, injection of hAMC-CM into infarcted rat hearts limited the infarct size, reduced cardiomyocyte apoptosis and ventricular remodeling, and strongly promoted capillary formation at the infarct border zone. Gene array analysis led to the identification of 32 genes encoding for the secreted factors overexpressed by hAMCs. Among these, midkine and secreted protein acidic and rich in cysteine were also upregulated at the protein level. Furthermore, high amounts of several proangiogenic factors were detected in hAMC-CM by cytokine array. Our results strongly support the concept that the administration of hAMC-CM favors the repair process after acute myocardial infarction.

The secretome of periodontal ligament stem cells from MS patients protects against EAE

“…On the contrary, EAE mice administered with RR-MS patients or donors hPDLSCs-CM and EMVs showed significant reduction in STAT1, p53, cleaved caspase 3 and Bax expressions. Anti-apoptotic effects of adult MSCs derived CM and EMVs in in vitro hypoxia and in vivo cardiac and kidney injury models have already been examined515253545556; however, most of these studies described the apoptosis regulatory effects in the context of microRNAs (miRNAs) present in MSCs secretions. From our results, we confirmed similar anti-apoptotic effects exerted from CM and EMVs of RR-MS patients and donors hPDLSCs.…”

Trophic Effects of Mesenchymal Stem Cells in Tissue Regeneration

“…87 The injection of MSC-CM into animal myocardial infarction models limited infarct size, reduced cardiomyocyte apoptosis and ventricular remodeling, and resulted in improved cardiac function compared with controls. 49,88,89 Meanwhile, extra cardiac administration of MSCs provided clear evidence that cardiac repair can be achieved through MSC's trophic actions and did not rely on their presence in the infarcted myocardium. 90 It should be emphasized that many of these positive effects of MSCs in AKI and myocardial infarction were found in animal models.…”

Cardiovascular Regenerative Technologies: Update and Future Outlook

“…Different studies contributed to the development of these technologies, like the in vitro and in vivo investigation of the secretome and extracellular vesicular content of MSCs. These studies led to the discovery of new cardioprotective molecules [28,29,30,31]. In this regard, Timmers et al [30] showed in 2007 the beneficial effects of MSC-conditioned medium upon injection in a pig model of ischemia/reperfusion, reporting a significant reduction in the ischemic myocardial area after the treatment.…”

“…In this regard, Timmers et al [30] showed in 2007 the beneficial effects of MSC-conditioned medium upon injection in a pig model of ischemia/reperfusion, reporting a significant reduction in the ischemic myocardial area after the treatment. More recently, the secretome of human amniotic membrane-derived MSCs was injected in infarcted rat models, leading to a reduction of the ischemic area and ventricular remodeling [28]. Although these promising studies are still at the preclinical level, they have the potential to shorten the distance from clinical trials to a possible therapeutic approach in humans [32].…”