Julian Gonzalez-Rubio, Kira Zeevaert, Eva Miriam Buhl, Michaela Schedel, Stefan Jockenhoevel, Christian G Cornelissen, Wolfgang Wagner, Anja Lena Thiebes
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引用次数: 0
Abstract
Aims: Mesenchymal stromal cells (MSCs) are being tested and accepted as a source for cell therapy worldwide. However, the advanced age of the patients, together with the difficulties in achieving the required cell amounts, impede autologous treatments. Reprogramming of MSCs into induced pluripotent stem cells (iPSCs), followed by re-differentiation to MSCs has emerged as a promising and safe method to facilitate the cell expansion and the removal of aging-associated characteristics. However, the effect of reprogramming on the MSC's pro-angiogenicity is poorly understood.
Materials and methods: In this study, we use a microfluidic organ-on-a-chip platform designed for vascularization assays to study and compare the effects of bone marrow MSCs (BM-MSCs) and iPSC-derived MSCs (iMSCs) in stimulating the formation of vessels by endothelial cells. Cells were loaded in fibrin hydrogels, injected into the microfluidic channel, and grown for ten days.
Key findings: Fluorescence microscopy revealed that BM-MSCs promote the formation of long and interconnected endothelial vessels, while iMSCs barely stimulate neoangiogenesis. This was further confirmed and explained by bulk RNA sequencing, showing a decrease of pro-angiogenic agents in both of the iMSCs co-cultures. Furthermore, transmission electron microscopy revealed that BM-MSCs closely associate with the new vessels as perivascular cells, while iMSCs just remain in proximity.
Significance: These results highlight iMSCs as a promising substitute for BM-MSCs in the treatment of diseases with pernicious vascularization, such as osteoarthritis, ocular degeneration, and cancer.
期刊介绍:
Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed.
The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.