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

Yin T, He S, Su C, Chen X, Zhang D, Wan Y, Ye T, Shen G, Wang Y, Shi H, Yang L, Wei Y - Mol Med Rep (2015)

Bottom Line: 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).Histological examination revealed markedly increased capillary and arteriole density in the Ad‑F‑P‑hPDMSC group.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.

View Article: PubMed Central - PubMed

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.

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‑ (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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Morphology and immunophenotype of hPDMSCs. (A) hPDMSCs adhered to plastic and exhibited spindle-like morphology. (B) Typical MSC markers on hPDMSCs were evaluated by flow cytometry. hPDMSCs were positive for CD29, CD90 and CD105, and negative for CD31. hPDMSCs, human placenta-derived MSCs; MSC, mesenchymal stem cell.
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f1-mmr-12-04-5093: Morphology and immunophenotype of hPDMSCs. (A) hPDMSCs adhered to plastic and exhibited spindle-like morphology. (B) Typical MSC markers on hPDMSCs were evaluated by flow cytometry. hPDMSCs were positive for CD29, CD90 and CD105, and negative for CD31. hPDMSCs, human placenta-derived MSCs; MSC, mesenchymal stem cell.

Mentions: Isolated cells were cultured on plastic in low-glucose DMEM selected for MSCs outgrowth. Roughly 6 days subsequent to seeding, adherent cells in small colonies with a spindle-like phenotype were visualized. The cells presented a large expansive potential following subculture. The spindle-like morphology, as displayed in Fig. 1A, was maintained throughout the culture period. Immunophenotype examination was performed to further identify the hPDMSCs. hPDMSCs expressed CD29, CD90 and CD105, and were negative for CD31 (Fig. 1B).


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

Yin T, He S, Su C, Chen X, Zhang D, Wan Y, Ye T, Shen G, Wang Y, Shi H, Yang L, Wei Y - Mol Med Rep (2015)

Morphology and immunophenotype of hPDMSCs. (A) hPDMSCs adhered to plastic and exhibited spindle-like morphology. (B) Typical MSC markers on hPDMSCs were evaluated by flow cytometry. hPDMSCs were positive for CD29, CD90 and CD105, and negative for CD31. hPDMSCs, human placenta-derived MSCs; MSC, mesenchymal stem cell.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581748&req=5

f1-mmr-12-04-5093: Morphology and immunophenotype of hPDMSCs. (A) hPDMSCs adhered to plastic and exhibited spindle-like morphology. (B) Typical MSC markers on hPDMSCs were evaluated by flow cytometry. hPDMSCs were positive for CD29, CD90 and CD105, and negative for CD31. hPDMSCs, human placenta-derived MSCs; MSC, mesenchymal stem cell.
Mentions: Isolated cells were cultured on plastic in low-glucose DMEM selected for MSCs outgrowth. Roughly 6 days subsequent to seeding, adherent cells in small colonies with a spindle-like phenotype were visualized. The cells presented a large expansive potential following subculture. The spindle-like morphology, as displayed in Fig. 1A, was maintained throughout the culture period. Immunophenotype examination was performed to further identify the hPDMSCs. hPDMSCs expressed CD29, CD90 and CD105, and were negative for CD31 (Fig. 1B).

Bottom Line: 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).Histological examination revealed markedly increased capillary and arteriole density in the Ad‑F‑P‑hPDMSC group.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.

View Article: PubMed Central - PubMed

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.

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‑ (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.

Show MeSH
Related in: MedlinePlus