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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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hPDMSC survival in the ischemic tissue. Immunohistochemical staining with an antibody against human-specific surface of intact mitochondria protein indicated that xenografted hPDMSCs survived in the ischemic tissue for at least four weeks. Scale bar, 50 µm; magnification ×3. hPDMSC, human placenta-derived mesenchymal stem cell. AD-F-P, adenoviral bicistronic vector containing FGF2 and PDGF-BB; ctrl, control without PDMSCs.
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f5-mmr-12-04-5093: hPDMSC survival in the ischemic tissue. Immunohistochemical staining with an antibody against human-specific surface of intact mitochondria protein indicated that xenografted hPDMSCs survived in the ischemic tissue for at least four weeks. Scale bar, 50 µm; magnification ×3. hPDMSC, human placenta-derived mesenchymal stem cell. AD-F-P, adenoviral bicistronic vector containing FGF2 and PDGF-BB; ctrl, control without PDMSCs.

Mentions: H&E staining was performed to detect the pathological changes in the ischemic muscles. No muscular atrophy or hemangioma was detected in any of the groups. In the Ad-F-P-hPDMSC group, numerous large cells aggregated in the intermuscular area. To evaluate whether the cells were transplanted ex vivo, sections were immunostained with a specific antibody against human mitochondria. The results indicated that several cells were positive for a human-specific marker (Fig. 5). These results suggest that the xenotransplanted hPDMSCs existed for at least 4 weeks in the ischemic muscle.


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)

hPDMSC survival in the ischemic tissue. Immunohistochemical staining with an antibody against human-specific surface of intact mitochondria protein indicated that xenografted hPDMSCs survived in the ischemic tissue for at least four weeks. Scale bar, 50 µm; magnification ×3. hPDMSC, human placenta-derived mesenchymal stem cell. AD-F-P, adenoviral bicistronic vector containing FGF2 and PDGF-BB; ctrl, control without PDMSCs.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5-mmr-12-04-5093: hPDMSC survival in the ischemic tissue. Immunohistochemical staining with an antibody against human-specific surface of intact mitochondria protein indicated that xenografted hPDMSCs survived in the ischemic tissue for at least four weeks. Scale bar, 50 µm; magnification ×3. hPDMSC, human placenta-derived mesenchymal stem cell. AD-F-P, adenoviral bicistronic vector containing FGF2 and PDGF-BB; ctrl, control without PDMSCs.
Mentions: H&E staining was performed to detect the pathological changes in the ischemic muscles. No muscular atrophy or hemangioma was detected in any of the groups. In the Ad-F-P-hPDMSC group, numerous large cells aggregated in the intermuscular area. To evaluate whether the cells were transplanted ex vivo, sections were immunostained with a specific antibody against human mitochondria. The results indicated that several cells were positive for a human-specific marker (Fig. 5). These results suggest that the xenotransplanted hPDMSCs existed for at least 4 weeks in the ischemic muscle.

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