Increased SCF/c-kit by hypoxia promotes autophagy of human placental chorionic plate-derived mesenchymal stem cells via regulating the phosphorylation of mTOR.

Hypoxia triggers physiological and pathological cellular processes, including proliferation, differentiation, and death, in several cell types. Mesenchymal stem cells (MSCs) derived from various tissues have self-renewal activity and can differentiate towards multiple lineages. Recently, it has been reported that hypoxic conditions tip the balance between survival and death by hypoxia-induced autophagy, although the underlying mechanism is not clear. The objectives of this study are to compare the effect of hypoxia on the self-renewal of bone marrow-derived mesenchymal stem cells (BM-MSCs) and placental chorionic plate-derived mesenchymal stem cells (CP-MSCs) and to investigate the regulatory mechanisms of self-renewal in each MSC type during hypoxia. The expression of self-renewal markers (e.g., Oct4, Nanog, Sox2) was assessed in both cell lines. PI3K and stem cell factor (SCF) expression gradually increased in CP-MSCs but were markedly downregulated in BM-MSCs by hypoxia. The phosphorylation of ERK and mTOR was augmented by hypoxia in CP-MSCs compared to control. Also, the expression of LC3 II, a component of the autophagosome and the hoof-shaped autophagosome was detected more rapidly in CP-MSCs than in BM-MSCs under hypoxia. Hypoxia induced the expression of SCF in CP-MSCs and increased SCF/c-kit pathway promotes the self-renewal activities of CP-MSCs via an autocrine/paracrine mechanism that balances cell survival and cell death events by autophagy. These activities occur to a greater extent in CP-MSCs than in BM-MSCs through regulating the phosphorylation of mTOR. These findings will provide useful guidelines for better understanding the function of SCF/c-kit in the self-renewal and autophagy-regulated mechanisms that promote of MSC survival.

Lee Y ，Jung J ，Cho KJ ，Lee SK ，Park JW ，Oh IH ，Kim GJ ... -  《-》

Human chorionic-plate-derived mesenchymal stem cells and Wharton's jelly-derived mesenchymal stem cells: a comparative analysis of their potential as placenta-derived stem cells.

Kim MJ ，Shin KS ，Jeon JH ，Lee DR ，Shim SH ，Kim JK ，Cha DH ，Yoon TK ，Kim GJ ... -  《-》

Knockdown of insulin-like growth factor 1 exerts a protective effect on hypoxic injury of aged BM-MSCs: role of autophagy.

Yang M ，Wen T ，Chen H ，Deng J ，Yang C ，Zhang Z ... -  《Stem Cell Research & Therapy》

Bone marrow-derived mesenchymal stem cells enhance autophagy via PI3K/AKT signalling to reduce the severity of ischaemia/reperfusion-induced lung injury.

Autophagy, a type II programmed cell death, is essential for cell survival under stress, e.g. lung injury, and bone marrow-derived mesenchymal stem cells (BM-MSCs) have great potential for cell therapy. However, the mechanisms underlying the BM-MSC activation of autophagy to provide a therapeutic effect in ischaemia/reperfusion-induced lung injury (IRI) remain unclear. Thus, we investigate the activation of autophagy in IRI following transplantation with BM-MSCs. Seventy mice were pre-treated with BM-MSCs before they underwent lung IRI surgery in vivo. Human pulmonary micro-vascular endothelial cells (HPMVECs) were pre-conditioned with BM-MSCs by oxygen-glucose deprivation/reoxygenation (OGD) in vitro. Expression markers for autophagy and the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signalling pathway were analysed. In IRI-treated mice, administration of BM-MSCs significantly attenuated lung injury and inflammation, and increased the level of autophagy. In OGD-treated HPMVECs, co-culture with BM-MSCs attenuated endothelial permeability by decreasing the level of cell death and enhanced autophagic activation. Moreover, administration of BM-MSCs decreased the level of PI3K class I and p-Akt while the expression of PI3K class III was increased. Finally, BM-MSCs-induced autophagic activity was prevented using the inhibitor LY294002. Administration of BM-MSCs attenuated lung injury by improving the autophagy level via the PI3K/Akt signalling pathway. These findings provide further understanding of the mechanisms related to BM-MSCs and will help to develop new cell-based therapeutic strategies in lung injury.

Li J ，Zhou J ，Zhang D ，Song Y ，She J ，Bai C ... -  《-》

Comparison of in vitro hepatogenic differentiation potential between various placenta-derived stem cells and other adult stem cells as an alternative source of functional hepatocytes.

Mesenchymal stem cells (MSCs) are powerful sources for cell therapy in regenerative medicine. The capability to obtain effective stem cell-derived hepatocytes would improve cell therapy for liver diseases. Recently, various placenta-derived stem cells (PDSCs) depending on the localization of placenta have been suggested as alternative sources of stem cells are similar to bone marrow-derived MSC (BM-MSCs) and adipose-derived MSC (AD-MSCs). However, comparative studies for the potentials of the hepatogenic differentiation among various MSCs largely lacking. Therefore, we investigated to compare the potentials for hepatogenic differentiation of PDSCs with BM-MSCs, AD-MSCs, and UCB-MSCs. Several MSCs were isolated from human term placenta, adipose tissue, and umbilical cord blood and characterized isolated MSCs and BM-MSCs was performed by quantitative reverse transcription-PCR (RT-PCR) and special stains after mesodermal differentiation. The hepatogenic potential of PDSCs was compared with AD-MSCs, UCB-MSCs, and BM-MSCs using RT-PCR, PAS stain, ICG up-take assays, albumin expression, urea production, and cytokine assays. MSCs isolated from different tissues all presented similar characteristics of MSCs. However, the proliferative potential of PDSCs and the expression of hepatogenic markers in differentiated PDSCs were higher than other MSCs. Interestingly, the expression of hepatocyte growth factor (HGF) increased in PDSCs after hepatogenic differentiation. Interestingly, stem cell factor (SCF) expression in chorionic plate-derived MSCs, one of the PDSCs, was significantly higher than in the other PDSCs. Taken together, the results of the present study suggest that MSCs isolated from various adult tissues can be induced to undergo hepatogenic differentiation in vitro, and that PDSCs may have the greatest potential for hepatogenic differentiation and proliferation. Therefore, PDSCs could be used as a stem cell source for cell therapy in liver diseases.

Lee HJ ，Jung J ，Cho KJ ，Lee CK ，Hwang SG ，Kim GJ ... -  《-》