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Hypoxia enhances tenocyte differentiation of adipose-derived mesenchymal stem cells by inducing hypoxia-inducible factor-1? in a co-culture system.

ABSTRACT: OBJECTIVES:Tissue engineering is a promising approach for repair of tendon injuries. Adipose-derived mesenchymal stem cells (ADMSCs) have gained increasing research interest for their potential in improving healing and regeneration of injured tendons. The present study aimed to investigate effects of O2 tension and potential signalling pathways on AMDSC differentiation into tenocytes, in an indirect co-culture system. MATERIALS AND METHODS:Human ADMSCs were co-cultured under normoxia (20% O2 ) and also under hypoxia (2% O2 ). Tenocyte differentiation of AMDSCs and expression of hypoxia-inducible factor-1 (HIF-1?) were analysed by reverse transcription-PCR, Western blotting and immunohistochemistry. Furthermore, HIF-1? inhibitor and inducer (FG-4592) effects on differentiation of AMDSCs were studied using qPCR, immunofluorescence and Western blotting. RESULTS:Indirect co-culture with tenocytes increased differentiation of ADMSCs into tenocytes; furthermore, hypoxia further enhanced tenocyte differentiation of AMDSCs, accompanied by increased expression of HIF-1?. HIF-1? inhibitor attenuated effects of hypoxia on differentiation of ADMSCs; in contrast, FG-4592 increased differentiation of ADMSCs under both hypoxia and normoxia. CONCLUSIONS:Taken together, we found that growing ADMSCs under hypoxia, or activating expression of HIF-1? to be important in differentiation of ADMSCs, which provides a foundation for application of ADMSCs in vivo for tendon regeneration.

SUBMITTER: Yu Y

PROVIDER: S-EPMC6496829 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Hypoxia enhances tenocyte differentiation of adipose-derived mesenchymal stem cells by inducing hypoxia-inducible factor-1α in a co-culture system.

Yu Yang Y Zhou Yulong Y Cheng Tao T Lu Xiaolang X Yu Kehe K Zhou Yifei Y Hong Jianjun J Chen Ying Y

Cell proliferation 20160329 2

<h4>Objectives</h4>Tissue engineering is a promising approach for repair of tendon injuries. Adipose-derived mesenchymal stem cells (ADMSCs) have gained increasing research interest for their potential in improving healing and regeneration of injured tendons. The present study aimed to investigate effects of O2 tension and potential signalling pathways on AMDSC differentiation into tenocytes, in an indirect co-culture system.<h4>Materials and methods</h4>Human ADMSCs were co-cultured under normo ...[more]

PMID: 27021233

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Project description:IntroductionMesenchymal stem cells (MSCs) have potential for the treatment of myocardial infarction. However, several meta-analyses revealed that the outcome of stem cell transplantation is dissatisfactory. A series of studies demonstrated that the combination of cell and gene therapy was a promising strategy to enhance therapeutic efficiency. The aim of this research is to investigate whether and how the combination of overexpression of hypoxia-inducible factor-1α (HIF-1α) and co-transplantation of mesenchymal stem cells can enhance cardiac repair in myocardial infarction.MethodsWe investigated the therapeutic effects of myocardial transfection of HIF-1α and co-transplantation of MSCs on cardiac repair in myocardial infarction by using myocardial transfection of HIF-1α via an adenoviral vector. Myocardial infarction was produced by coronary ligation in Sprague-Dawley (SD) rats. Animals were divided randomly into six groups: (1) HIF-1α+MSCs group: Ad-HIF-1α (6×10⁹ plate forming unit) and MSCs (1×10⁶) were intramyocardially injected into the border zone simultaneously; (2) HIF-1α group: Ad-HIF-1α (6×10⁹ plate forming unit) was injected into the border zone; (3) HIF-1α-MSCs group: Ad-HIF-1α transfected MSCs (1×10⁶) were injected into the border zone; (4) MSCs group: MSCs (1×10⁶) were injected into the border zone; (5) CONTROL GROUP: same volume of DMEM was injected; (6) SHAM group. Cardiac performance was then quantified by echocardiography as well as molecular and pathologic analysis of heart samples in the peri-infarcted region and the infarcted region at serial time points. The survival and engraftment of transplanted MSCs were also assessed.ResultsMyocardial transfection of HIF-1α combined with MSC transplantation in the peri-infarcted region improved cardiac function four weeks after myocardial infarction. Significant increases in vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1α (SDF-1α) expression, angiogenesis and MSC engraftment, as well as decreased cardiomyocyte apoptosis in peri-infarcted regions in the hearts of the HIF-1α+MSCs group were detected compared to the MSCs group and Control group.ConclusionsThese findings suggest that myocardial transfection of HIF-1α and co-transplantation of mesenchymal stem cells enhance cardiac repair in myocardial infarction, indicating the feasibility and preliminary safety of a combination of myocardial transfection of HIF-1α and MSC transplantation to treat myocardial infarction.

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Hypoxia enhances tenocyte differentiation of adipose-derived mesenchymal stem cells by inducing hypoxia-inducible factor-1? in a co-culture system.

Publications

Hypoxia enhances tenocyte differentiation of adipose-derived mesenchymal stem cells by inducing hypoxia-inducible factor-1α in a co-culture system.

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