Mesenchymal stem cells from human umbilical cord express preferentially secreted factors related to neuroprotection, neurogenesis, and angiogenesis.




August 2013 | Volume 8 | Issue 8 | e72604   doi:10.1371/journal.pone.0072604

Jui-Yu Hsieh1☯, Hsei-Wei Wang1,3,4☯, Shing-Jyh Chang2, Ko-Hsun Liao1,5, I-Hui Lee5,6, Wei-Shiang Lin7, Chun-Hsien Wu7, Wen-Yu Lin7, Shu-Meng Cheng7*



Mesenchymal stem cells (MSCs) are promising tools for the treatment of diseases such as infarcted myocardia and strokes because of their ability to promote endogenous angiogenesis and neurogenesis via a variety of secreted factors. MSCs found in the Wharton’s jelly of the human umbilical cord are easily obtained and are capable of transplantation without rejection. We isolated MSCs from Wharton’s jelly and bone marrow (WJ-MSCs and BM-MSCs, respectively) and compared their secretomes. It was found that WJ-MSCs expressed more genes, especially secreted factors, involved in angiogenesis and neurogenesis. Functional validation showed that WJ-MSCs induced better neural differentiation and neural cell migration via a paracrine mechanism. Moreover, WJ-MSCs afforded better neuroprotection efficacy because they preferentially enhanced neuronal growth and reduced cell apoptotic death of primary cortical cells in an oxygen-glucose deprivation (OGD) culture model that mimics the acute ischemic stroke situation in humans. In terms of angiogenesis, WJ-MSCs induced better microvasculature formation and cell migration on co-cultured endothelial cells. Our results suggest that WJ-MSC, because of a unique secretome, is a better MSC source to promote in vivo neurorestoration and endothelium repair. This study provides a basis for the development of cell-based therapy and carrying out of follow-up mechanistic studies related to MSC biology.



Our results confirmed that WJ-MSCs secreted highly levels of CXCL5 compared with BM-MSCs. Administration of CXCL5 can enhance HUVEC proliferation, invasion and tube formation abilities [62]. CXCL5 has been reported as an angiogenic factor in non-small cell lung cancer, where the protein level of CXCL5 is positively correlated with tumor vessel density [63]. CXCL5 secreted by rat adipose tissue-derived stem cells also has neurotrophic effects on rat major pelvic ganglia [64]. However, secreted levels of CXCL5 were hard to be detected in human BM-MSC and adipose tissue MSC conditioned medium [28]. The importance of CXCL5 in WJ-MSC conditioned medium related to neuroprotective, neurogenesis and angiogenesis will need further investigation.


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