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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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Assessment of capillary density. (A) Ischemic muscle sections were stained with an antibody against CD31 to evaluate capillary density. A greater density of capillaries was observed in the Ad-F-P-hPDMSC group. Scale bar, 50 µm. (B) Quantification of capillary density in ischemic muscles. *P<0.05 vs. control. 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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f4-mmr-12-04-5093: Assessment of capillary density. (A) Ischemic muscle sections were stained with an antibody against CD31 to evaluate capillary density. A greater density of capillaries was observed in the Ad-F-P-hPDMSC group. Scale bar, 50 µm. (B) Quantification of capillary density in ischemic muscles. *P<0.05 vs. control. 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 further evaluate the impact of genetically modified hPDMSCs on the formation of capillaries in the ischemic area, histological examination of ischemic adductor muscle was performed. Capillary density in the Ad-F-P-hPDMSC group was higher than in other groups (Fig. 4). However, no significant difference was detected between the Ad--hPDMSC, hPDMSC and control groups.


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)

Assessment of capillary density. (A) Ischemic muscle sections were stained with an antibody against CD31 to evaluate capillary density. A greater density of capillaries was observed in the Ad-F-P-hPDMSC group. Scale bar, 50 µm. (B) Quantification of capillary density in ischemic muscles. *P<0.05 vs. control. 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

f4-mmr-12-04-5093: Assessment of capillary density. (A) Ischemic muscle sections were stained with an antibody against CD31 to evaluate capillary density. A greater density of capillaries was observed in the Ad-F-P-hPDMSC group. Scale bar, 50 µm. (B) Quantification of capillary density in ischemic muscles. *P<0.05 vs. control. 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 further evaluate the impact of genetically modified hPDMSCs on the formation of capillaries in the ischemic area, histological examination of ischemic adductor muscle was performed. Capillary density in the Ad-F-P-hPDMSC group was higher than in other groups (Fig. 4). However, no significant difference was detected between the Ad--hPDMSC, hPDMSC and control groups.

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