title: Genetically modified human placenta‑derived mesenchymal stem cells with FGF‑2 and PDGF‑BB enhance neovascularization in a model of hindlimb ischemia.
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.
authors.affiliation: 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.
authors.forename: Tao
authors.initials: T
authors.lastname: Yin
authors.affiliation: 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.
authors.forename: Sisi
authors.initials: S
authors.lastname: He
authors.affiliation: 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.
authors.forename: Chao
authors.initials: C
authors.lastname: Su
authors.affiliation: 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.
authors.forename: Xiancheng
authors.initials: X
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wan
authors.affiliation: 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.
authors.forename: Tinghong
authors.initials: T
authors.lastname: Ye
authors.affiliation: 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.
authors.forename: Guobo
authors.initials: G
authors.lastname: Shen
authors.affiliation: 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.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Huashan
authors.initials: H
authors.lastname: Shi
authors.affiliation: 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.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000077214:Becaplermin; D049109:Cell Proliferation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D004195:Disease Models, Animal; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D005818:Genetic Engineering; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D006614:Hindlimb / Q000098:blood supply / Q000473:pathology; D006801:Humans; D007511:Ischemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D010920:Placenta / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D061251:Primary Cell Culture; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics* / Q000378:metabolism; D011817:Rabbits; D014162:Transfection; D019076:Transgenes
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin