MSC-derived cytokines repair radiation-induced intra-villi microvascular injury

Abstract

Microvascular injury initiates the pathogenesis of radiation enteropathy. As previously demonstrated, the secretome from mesenchymal stem cells contains various angiogenic cytokines that exhibited therapeutic potential for ischemic lesions. As such, the present study aimed to investigate whether cytokines derived from mesenchymal stem cells can repair endothelial injuries from irradiated intestine. Here, serum-free medium was conditioned by human adipose-derived mesenchymal stem cells, and we found that there were several angiogenic cytokines in the medium, including IL-8, angiogenin, HGF and VEGF. This medium promoted the formation of tubules between human umbilical cord vein endothelial cells and protected these cells against radiation-induced apoptosis in vitro. Likewise, our in vivo results revealed that repeated injections of mesenchymal stem cell-conditioned medium could accelerate the recovery of irradiated mice by reducing the serum levels of pro-inflammatory cytokines, including IL-1α, IL-6 and TNF-α, and promoting intra-villi angiogenesis. Herein, intervention by conditioned medium could increase the number of circulating endothelial progenitors, whereas neutralizing SDF-1α and/or inhibiting PI3K would hamper the recruitment of endothelial progenitors to the injured sites. Such results suggested that SDF-1α and PI3K-mediated phosphorylation were required for intra-villi angiogenesis. To illustrate this, we found that conditioned medium enabled endothelial cells to increase intracellular levels of phosphorylated Akt Ser473, both under irradiated and steady state conditions, and to up-regulate the expression of the CXCR4 and CXCR7 genes. Collectively, the present results revealed the therapeutic effects of mesenchymal stem cell-derived cytokines on microvascular injury of irradiated intestine.

Modifiers of mesenchymal stem cell quantity and quality

“…In contrast, BM‐MSCs secreted only two (IL‐8 and RANTES) cytokines at higher amounts at P3 compared to P1, and secretion of six cytokines and growth factors (fractalkine, PGDF‐BB, IL‐2, IL‐6, IL‐8, and RANTES) was significantly increased at P5 compared to P1. Multiple studies indicate that the biologic functions mediated by MSCs are dependent on cytokine release by the MSC . Since the cytokine secretion profiles of both AD‐MSC and BM‐MSC seem to be passage dependent, it stands to reason that MSC passage number would also influence their biological potency.…”

“…Multiple studies indicate that the biologic functions mediated by MSCs are dependent on cytokine release by the MSC. [14][15][16] Since the cytokine secretion profiles of both AD-MSC and BM-MSC seem to be passage dependent, it stands to reason that MSC passage number would also influence their biological potency. When we compared overall cytokine and growth factor secretion by AD-MSCs with BM-MSCs at P3, we found that AD-MSCs significantly secreted a higher number of cytokines and growth factors at greater concentrations.…”

Human umbilical cord MSC‑derived hepatocyte growth factor enhances autophagy in AOPP‑treated HK‑2 cells

“…Kennelly et al (31) reported that human MSC-derived HGF exerted an antiapoptotic effect in chronic obstructive pulmonary disease. Chang et al (32) determined that several angiogenic cytokines, including HGF, protected endothelial cells against radiation-induced apoptosis and accelerated the recovery of irradiated mice. To determine whether HGF enhanced autophagy, the present study investigated HK-2 cells treated with rhHGF and the results suggested that rhHGF increased HK-2 cell autophagy.…”

Conditioned medium from primary cytotrophoblasts, primary placenta-derived mesenchymal stem cells, or placental tissue promoted HUVECs angiogenesis in vitro

“…In addition, it is unknown whether longer culture times result in more robust effects. A study by Chang, used different time points, including 6, 12, 24, 48, and 72 hours for placental cell-derived CM [47] and 1, 3, 5, 7, 10, and 14 days for placental tissue-derived CM, to achieve optimal effects. The results showed that the optimal time points for placental cell-derived CM were 24 and 48 hours but not 72 hours.…”