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Ultrasound-targeted stromal cell-derived factor-1-loaded microbubble destruction promotes mesenchymal stem cell homing to kidneys in diabetic nephropathy rats.

Wu S, Li L, Wang G, Shen W, Xu Y, Liu Z, Zhuo Z, Xia H, Gao Y, Tan K - Int J Nanomedicine (2014)

Bottom Line: The related bioeffects were also elucidated.In the in vivo study, SDF-1 was successfully released in the targeted kidneys.In conclusion, ultrasound-targeted MB(SDF-1) destruction could promote the homing of MSCs to early DN kidneys and provide a novel potential therapeutic approach for DN kidney repair.

View Article: PubMed Central - PubMed

Affiliation: Department of Ultrasound, Third Military Medical University, Chongqing, People's Republic of China.

ABSTRACT
Mesenchymal stem cell (MSC) therapy has been considered a promising strategy to cure diabetic nephropathy (DN). However, insufficient MSCs can settle in injured kidneys, which constitute one of the major barriers to the effective implementation of MSC therapy. Stromal cell-derived factor-1 (SDF-1) plays a vital role in MSC migration and involves activation, mobilization, homing, and retention, which are presumably related to the poor homing in DN therapy. Ultrasound-targeted microbubble destruction has become one of the most promising strategies for the targeted delivery of drugs and genes. To improve MSC homing to DN kidneys, we present a strategy to increase SDF-1 via ultrasound-targeted microbubble destruction. In this study, we developed SDF-1-loaded microbubbles (MB(SDF-1)) via covalent conjugation. The characterization and bioactivity of MB(SDF-1) were assessed in vitro. Target release in the targeted kidneys was triggered with diagnostic ultrasound in combination with MB(SDF-1). The related bioeffects were also elucidated. Early DN was induced in rats with streptozotocin. Green fluorescent protein-labeled MSCs were transplanted intravenously following the target release of SDF-1 in the kidneys of normal and DN rats. The homing efficacy was assessed by detecting the implanted exogenous MSCs at 24 hours. The in vitro results showed an impressive SDF-1 loading efficacy of 79% and a loading content of 15.8 μg/mL. MB(SDF-1) remained bioactive as a chemoattractant. In the in vivo study, SDF-1 was successfully released in the targeted kidneys. The homing efficacy of MSCs to DN kidneys after the target release of SDF-1 was remarkably ameliorated at 24 hours compared with control treatments in normal rats and DN rats. In conclusion, ultrasound-targeted MB(SDF-1) destruction could promote the homing of MSCs to early DN kidneys and provide a novel potential therapeutic approach for DN kidney repair.

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Target release in kidney under CLSM.Notes: No fluorescence was found in the control kidney (upper panel in [A]). After UTMD with FITC-MBSDF-1, sporadic green fluorescence in the renal interstitium and around the small vessels was observed under a CLSM (lower panel in [A]). (B) A significantly higher mean gray-scale value in the target kidney (left kidney) compared to any other major organs; *P<0.05 (P-value of 9.85×10−10 versus heart, 7.57×10−10 versus lung, 2.34×10−10 versus liver, 5.78×10−10 versus spleen, and 4.59×10−10 versus right kidney).Abbreviations: CLSM, confocal laser scanning microscope; UTMD, ultrasound-targeted microbubble destruction; FITC-MBSDF-1, fluorescein isothiocyanate-labeled stromal cell-derived factor-1-loaded microbubbles; DAPI, 4′,6-diamidino-2-phenylindole.
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f6-ijn-9-5639: Target release in kidney under CLSM.Notes: No fluorescence was found in the control kidney (upper panel in [A]). After UTMD with FITC-MBSDF-1, sporadic green fluorescence in the renal interstitium and around the small vessels was observed under a CLSM (lower panel in [A]). (B) A significantly higher mean gray-scale value in the target kidney (left kidney) compared to any other major organs; *P<0.05 (P-value of 9.85×10−10 versus heart, 7.57×10−10 versus lung, 2.34×10−10 versus liver, 5.78×10−10 versus spleen, and 4.59×10−10 versus right kidney).Abbreviations: CLSM, confocal laser scanning microscope; UTMD, ultrasound-targeted microbubble destruction; FITC-MBSDF-1, fluorescein isothiocyanate-labeled stromal cell-derived factor-1-loaded microbubbles; DAPI, 4′,6-diamidino-2-phenylindole.

Mentions: Immediately after UTMD using FITC-MBSDF-1, frozen sections of the kidneys exhibited sporadic but bright green fluorescence (Figure 6A). The fluorescence mainly distributed around the small vessels and into the adjacent renal interstitium. In comparison, fluorescence was not visualized in the kidneys without UTMD treatment as well as in the spleens, and fluorescence was rare in the hearts, lungs, and livers. The mean gray-scale value of the targeted kidney was significantly higher than those of any other control organs (Figure 6B), indicating that the loaded SDF-1 was successfully released in the targeted kidney tissues.


Ultrasound-targeted stromal cell-derived factor-1-loaded microbubble destruction promotes mesenchymal stem cell homing to kidneys in diabetic nephropathy rats.

Wu S, Li L, Wang G, Shen W, Xu Y, Liu Z, Zhuo Z, Xia H, Gao Y, Tan K - Int J Nanomedicine (2014)

Target release in kidney under CLSM.Notes: No fluorescence was found in the control kidney (upper panel in [A]). After UTMD with FITC-MBSDF-1, sporadic green fluorescence in the renal interstitium and around the small vessels was observed under a CLSM (lower panel in [A]). (B) A significantly higher mean gray-scale value in the target kidney (left kidney) compared to any other major organs; *P<0.05 (P-value of 9.85×10−10 versus heart, 7.57×10−10 versus lung, 2.34×10−10 versus liver, 5.78×10−10 versus spleen, and 4.59×10−10 versus right kidney).Abbreviations: CLSM, confocal laser scanning microscope; UTMD, ultrasound-targeted microbubble destruction; FITC-MBSDF-1, fluorescein isothiocyanate-labeled stromal cell-derived factor-1-loaded microbubbles; DAPI, 4′,6-diamidino-2-phenylindole.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4263441&req=5

f6-ijn-9-5639: Target release in kidney under CLSM.Notes: No fluorescence was found in the control kidney (upper panel in [A]). After UTMD with FITC-MBSDF-1, sporadic green fluorescence in the renal interstitium and around the small vessels was observed under a CLSM (lower panel in [A]). (B) A significantly higher mean gray-scale value in the target kidney (left kidney) compared to any other major organs; *P<0.05 (P-value of 9.85×10−10 versus heart, 7.57×10−10 versus lung, 2.34×10−10 versus liver, 5.78×10−10 versus spleen, and 4.59×10−10 versus right kidney).Abbreviations: CLSM, confocal laser scanning microscope; UTMD, ultrasound-targeted microbubble destruction; FITC-MBSDF-1, fluorescein isothiocyanate-labeled stromal cell-derived factor-1-loaded microbubbles; DAPI, 4′,6-diamidino-2-phenylindole.
Mentions: Immediately after UTMD using FITC-MBSDF-1, frozen sections of the kidneys exhibited sporadic but bright green fluorescence (Figure 6A). The fluorescence mainly distributed around the small vessels and into the adjacent renal interstitium. In comparison, fluorescence was not visualized in the kidneys without UTMD treatment as well as in the spleens, and fluorescence was rare in the hearts, lungs, and livers. The mean gray-scale value of the targeted kidney was significantly higher than those of any other control organs (Figure 6B), indicating that the loaded SDF-1 was successfully released in the targeted kidney tissues.

Bottom Line: The related bioeffects were also elucidated.In the in vivo study, SDF-1 was successfully released in the targeted kidneys.In conclusion, ultrasound-targeted MB(SDF-1) destruction could promote the homing of MSCs to early DN kidneys and provide a novel potential therapeutic approach for DN kidney repair.

View Article: PubMed Central - PubMed

Affiliation: Department of Ultrasound, Third Military Medical University, Chongqing, People's Republic of China.

ABSTRACT
Mesenchymal stem cell (MSC) therapy has been considered a promising strategy to cure diabetic nephropathy (DN). However, insufficient MSCs can settle in injured kidneys, which constitute one of the major barriers to the effective implementation of MSC therapy. Stromal cell-derived factor-1 (SDF-1) plays a vital role in MSC migration and involves activation, mobilization, homing, and retention, which are presumably related to the poor homing in DN therapy. Ultrasound-targeted microbubble destruction has become one of the most promising strategies for the targeted delivery of drugs and genes. To improve MSC homing to DN kidneys, we present a strategy to increase SDF-1 via ultrasound-targeted microbubble destruction. In this study, we developed SDF-1-loaded microbubbles (MB(SDF-1)) via covalent conjugation. The characterization and bioactivity of MB(SDF-1) were assessed in vitro. Target release in the targeted kidneys was triggered with diagnostic ultrasound in combination with MB(SDF-1). The related bioeffects were also elucidated. Early DN was induced in rats with streptozotocin. Green fluorescent protein-labeled MSCs were transplanted intravenously following the target release of SDF-1 in the kidneys of normal and DN rats. The homing efficacy was assessed by detecting the implanted exogenous MSCs at 24 hours. The in vitro results showed an impressive SDF-1 loading efficacy of 79% and a loading content of 15.8 μg/mL. MB(SDF-1) remained bioactive as a chemoattractant. In the in vivo study, SDF-1 was successfully released in the targeted kidneys. The homing efficacy of MSCs to DN kidneys after the target release of SDF-1 was remarkably ameliorated at 24 hours compared with control treatments in normal rats and DN rats. In conclusion, ultrasound-targeted MB(SDF-1) destruction could promote the homing of MSCs to early DN kidneys and provide a novel potential therapeutic approach for DN kidney repair.

Show MeSH
Related in: MedlinePlus