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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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Angiographic assessment of collateral vessel formation. (A) Angiography was performed 28 days after cell therapy. More collateral vessels were visualized in the Ad-F-P-hPDMSC group. (B) Quantification of angiographic score. Genetically-modified hPDMSCs robustly enhanced collateral vessel formation. *P<0.05 vs. control group. hPDMSC, human placenta-derived mesenchymal stem cell; AD-F-P, adenoviral bicistronic vector containing FGF2 and PDGF-BB; Ad-, control vector; ctrl, control without PDMSCs.
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f2-mmr-12-04-5093: Angiographic assessment of collateral vessel formation. (A) Angiography was performed 28 days after cell therapy. More collateral vessels were visualized in the Ad-F-P-hPDMSC group. (B) Quantification of angiographic score. Genetically-modified hPDMSCs robustly enhanced collateral vessel formation. *P<0.05 vs. control group. hPDMSC, human placenta-derived mesenchymal stem cell; AD-F-P, adenoviral bicistronic vector containing FGF2 and PDGF-BB; Ad-, control vector; ctrl, control without PDMSCs.

Mentions: To test whether genetically modified hPDMSCs were able to enhance collateral vessel formation in a model of ischemia, angiography was performed at 28 days subsequent to cell therapy. Greater collateral vessel formation was observed in the hindlimbs of Ad-F-P-hPDMSC-treated rabbits compared with those of other groups (Fig. 2A). Quantitative analysis of collateral vessels demonstrated that the angiographic score in the Ad-F-P-hPDMSC group was significantly higher than that of the control group (Fig. 2B). hPDMSCs alone did not significantly induce collateral vessel formation, although the average angiographic score was higher in the hPDMSC group compared with that of the control group. These results suggest that the delivery of genetically-modified hPDMSCs with FGF2 and PDGF-BB has a greater ability to induce robust arteriogenesis compared with hPDMSCs alone.


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)

Angiographic assessment of collateral vessel formation. (A) Angiography was performed 28 days after cell therapy. More collateral vessels were visualized in the Ad-F-P-hPDMSC group. (B) Quantification of angiographic score. Genetically-modified hPDMSCs robustly enhanced collateral vessel formation. *P<0.05 vs. control group. hPDMSC, human placenta-derived mesenchymal stem cell; AD-F-P, adenoviral bicistronic vector containing FGF2 and PDGF-BB; Ad-, control vector; ctrl, control without PDMSCs.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2-mmr-12-04-5093: Angiographic assessment of collateral vessel formation. (A) Angiography was performed 28 days after cell therapy. More collateral vessels were visualized in the Ad-F-P-hPDMSC group. (B) Quantification of angiographic score. Genetically-modified hPDMSCs robustly enhanced collateral vessel formation. *P<0.05 vs. control group. hPDMSC, human placenta-derived mesenchymal stem cell; AD-F-P, adenoviral bicistronic vector containing FGF2 and PDGF-BB; Ad-, control vector; ctrl, control without PDMSCs.
Mentions: To test whether genetically modified hPDMSCs were able to enhance collateral vessel formation in a model of ischemia, angiography was performed at 28 days subsequent to cell therapy. Greater collateral vessel formation was observed in the hindlimbs of Ad-F-P-hPDMSC-treated rabbits compared with those of other groups (Fig. 2A). Quantitative analysis of collateral vessels demonstrated that the angiographic score in the Ad-F-P-hPDMSC group was significantly higher than that of the control group (Fig. 2B). hPDMSCs alone did not significantly induce collateral vessel formation, although the average angiographic score was higher in the hPDMSC group compared with that of the control group. These results suggest that the delivery of genetically-modified hPDMSCs with FGF2 and PDGF-BB has a greater ability to induce robust arteriogenesis compared with hPDMSCs alone.

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