Genetically modified human placenta‑derived mesenchymal stem cells with FGF‑2 and PDGF‑BB enhance neovascularization in a model of hindlimb ischemia

Yin,Tao; He,Sisi; Su,Chao; Chen,Xiancheng; Zhang,Dongmei; Wan,Yang; Ye,Tinghong; Shen,Guobo; Wang,Yongsheng; Shi,Huashan; Yang,Li; Wei,Yuquan

doi:10.3892/mmr.2015.4089

Genetically modified human placenta‑derived mesenchymal stem cells with FGF‑2 and PDGF‑BB enhance neovascularization in a model of hindlimb ischemia

Authors:
- Tao Yin
- Sisi He
- Chao Su
- Xiancheng Chen
- Dongmei Zhang
- Yang Wan
- Tinghong Ye
- Guobo Shen
- Yongsheng Wang
- Huashan Shi
- Li Yang
- Yuquan Wei
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Affiliations: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, P.R. China
Published online on: July 20, 2015 https://doi.org/10.3892/mmr.2015.4089
Pages: 5093-5099
Copyright: © Yin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ischemic diseases represent a challenging worldwide health burden. The current study investigated the therapeutic potential of genetically modified human placenta‑derived mesenchymal stem cells (hPDMSCs) with basic fibroblast growth factor (FGF2) and platelet‑derived growth factor‑BB (PDGF‑BB) genes in hindlimb ischemia. Mesenchymal stem cells obtained from human term placenta were transfected ex vivo with adenoviral bicistronic vectors carrying the FGF2 and PDGF‑BB genes (Ad‑F‑P). Unilateral hindlimb ischemia was surgically induced by excision of the right femoral artery in New Zealand White rabbits. Ad‑F‑P genetically modified hPDMSCs, Ad‑null (control vector)‑modified hPDMSCs, unmodified hPDMSCs or media were intramuscularly implanted into the ischemic limbs 7 days subsequent to the induction of ischemia. Four weeks after cell therapy, angiographic analysis revealed significantly increased collateral vessel formation in the Ad‑F‑P‑hPDMSC group compared with the control group. Histological examination revealed markedly increased capillary and arteriole density in the Ad‑F‑P‑hPDMSC group. The xenografted hPDMSCs survived in the ischemic tissue for at least 4 weeks subsequent to cell therapy. The current study demonstrated that the combination of hPDMSC therapy with FGF2 and PDGF‑BB gene therapy effectively induced collateral vessel formation and angiogenesis, suggesting a novel strategy for therapeutic angiogenesis.

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