bFGF promotes Sca‑1+ cardiac stem cell migration through activation of the PI3K/Akt pathway

Ling,Lin; Gu,Shaohua; Cheng,Yan; Ding,Liucheng

doi:10.3892/mmr.2017.8178

bFGF promotes Sca‑1+ cardiac stem cell migration through activation of the PI3K/Akt pathway

Authors:
- Lin Ling
- Shaohua Gu
- Yan Cheng
- Liucheng Ding
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Affiliations: Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Nephrology, The Third People's Hospital of Kunshan, Kunshan, Jiangsu 215300, P.R. China, Department of Cardiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu 214000, P.R. China, Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China
Published online on: November 28, 2017 https://doi.org/10.3892/mmr.2017.8178
Pages: 2349-2356
Copyright: © Ling et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cardiac stem cells (CSCs) are important for improving cardiac function following myocardial infarction, with CSC migration to infarcted or ischemic myocardium important for cardiac regeneration. Strategies to improve cell migration may improve the efficiency of myocardial regeneration. Basic fibroblast growth factor (bFGF) is an essential molecule in cell migration, but the endogenous bFGF level is too low to be effective. The effect of exogenously delivered bFGF on CSC migration was observed in vitro and in vivo in the present study. The CSC migration index in response to various bFGF concentrations was demonstrated in vitro. In addition, a murine myocardial infarction model was constructed and bFGF protein expression levels and CSC aggregation following myocardial infarction were observed. To study cell migration in vivo, CM‑Dil‑labeled CSCs or bFGF‑CSCs were injected into the peri‑infarct myocardium following myocardium infarction and cell migration and maintenance in the peri‑infarct/infarct area was observed 1 week later. Protein expression levels of bFGF, CXCR‑4 and SDF‑1 were assessed, as was myocardium capillary density. The Akt inhibitor deguelin was used to assess the role of the PI3K/Akt pathway in vitro and in vivo. The present study demonstrated that bFGF‑promoted Sca‑1+ CSC migration, with the highest migration rate occurring at a concentration of 45 ng/ml. The PI3K/Akt pathway inhibitor deguelin attenuated this increase. The phospho‑Akt/Akt ratio was elevated significantly after 30 min of bFGF exposure. Transplantation of bFGF‑treated Sca‑1+ CSCs led to improved cell maintenance in the peri‑infarct area and increased cell migration to the infarct area, as well as improved angiogenesis. Protein expression levels of bFGF, CXCR‑4 and SDF‑1 were upregulated, and this upregulation was partially attenuated by deguelin. Therefore, bFGF was demonstrated to promote Sca‑1+ CSC migration both in vitro and in vivo, partially through activation of the PI3K/Akt pathway. This may provide a new method for facilitating CSC therapy for myocardium repair after myocardium injury.

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