Co-expression of Akt1 and Wnt11 promotes the proliferation and cardiac differentiation of mesenchymal stem cells and attenuates hypoxia/reoxygenation-induced cardiomyocyte apoptosis

Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie
Bangdang ChenYing Huang

Abstract

Mesenchymal stem cells (MSCs) transplantation has emerged as a promising therapeutic strategy for acute myocardial infarction. However, there are still limitations for this therapy, such as low survival rate and poor cardiac differentiation potential of MSCs. In this study, we genetically engineered MSCs using ex vivo adeno-associated virus (AAV) transduction to overexpress Akt1 and Wnt11, which are well-characterized genes involved in MSC proliferation and cardiac differentiation. Our results showed that infection with AAV-Akt1-Wnt11 significantly upregulated the growth and proliferation of MSCs, as compared with those infected with AAV-Akt1 or AAV-Wnt11. In addition, co-expression of Akt1 and Wnt11 markedly promoted the expression of cardiac markers including NK2 transcription factor related 5, GATA-binding protein 4, α-myosin MHC and brain natriuretic protein. Notably, co-expression of Akt1 and Wnt11 increased cell survival and reduced cell apoptosis of MSCs under hypoxia/reoxygenation (H/R) treatment; however, these effects were blocked by Wnt11 neutralizing antibodies or Akt1 inhibitor. Moreover, co-culture of cardiomyocytes with MSCs infected with AAV-Akt1-Wnt11, in a dual chamber system, significantly reduced H/R-induced...Continue Reading

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Citations

May 19, 2019·Circulation. Genomic and Precision Medicine·Farnaz Shoja-TaheriMichael E Davis
Aug 24, 2019·Current Stem Cell Research & Therapy·Wei ChenMing Lu
Sep 26, 2020·Frontiers in Cell and Developmental Biology·Patricia Kauanna Fonseca DamascenoMilena Botelho Pereira Soares
Jun 1, 2021·Frontiers in Cell and Developmental Biology·Qiong LiZhikun Guo
Aug 10, 2021·Frontiers in Cell and Developmental Biology·Yanlei YangRobert Chunhua Zhao

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