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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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In vivo imaging and ultrasound-targeted microbubble destruction.Notes: (A) At a low mechanical index, the renal parenchyma apparently improved after MBSDF-1 infusion, compared with adjacent tissues. After 4 seconds of MBD at a high mechanical index (B), the MBs in the renal parenchyma almost disappeared, showing a low acoustic intensity (C). (D–F) Within 3–4 seconds, the MBs gradually replenished until complete recovery. (G) The rectangular region of interest was positioned in the renal parenchyma (red) and the adjacent tissue at the same depth (blue). (H) The derived time–intensity curve indicated a sudden echo intensity decrease during MBD and a gradual ascending recovery.Abbreviations: MBSDF-1, stromal cell-derived factor-1-loaded microbubbles; MBD, microbubble destruction; MBs, microbubbles.
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f4-ijn-9-5639: In vivo imaging and ultrasound-targeted microbubble destruction.Notes: (A) At a low mechanical index, the renal parenchyma apparently improved after MBSDF-1 infusion, compared with adjacent tissues. After 4 seconds of MBD at a high mechanical index (B), the MBs in the renal parenchyma almost disappeared, showing a low acoustic intensity (C). (D–F) Within 3–4 seconds, the MBs gradually replenished until complete recovery. (G) The rectangular region of interest was positioned in the renal parenchyma (red) and the adjacent tissue at the same depth (blue). (H) The derived time–intensity curve indicated a sudden echo intensity decrease during MBD and a gradual ascending recovery.Abbreviations: MBSDF-1, stromal cell-derived factor-1-loaded microbubbles; MBD, microbubble destruction; MBs, microbubbles.

Mentions: After MBSDF-1 infusion, the echogenicity of renal parenchyma was markedly enhanced, with an explicit border at a low MI of 0.05 (Figure 4A). During 4 seconds of MBD at a high MI of 1.5, the MBs were destroyed from the near acoustic field to the far acoustic field (Figure 4B). Immediately after MBD, the MBs in the parenchyma almost vanished, leaving a hypo-echoic and blurred renal outline (Figure 4C). Within 4 seconds, the circulating MBs gradually and smoothly replenished until the perfusion of renal MBs completely recovered (Figure 4C–F). The time–intensity curve obtained from contrast dynamic analysis indicated a relative hyper-echo before MBD, a sudden decrease during MBD, and a gradually increasing recovery process (Figure 4G and H).


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)

In vivo imaging and ultrasound-targeted microbubble destruction.Notes: (A) At a low mechanical index, the renal parenchyma apparently improved after MBSDF-1 infusion, compared with adjacent tissues. After 4 seconds of MBD at a high mechanical index (B), the MBs in the renal parenchyma almost disappeared, showing a low acoustic intensity (C). (D–F) Within 3–4 seconds, the MBs gradually replenished until complete recovery. (G) The rectangular region of interest was positioned in the renal parenchyma (red) and the adjacent tissue at the same depth (blue). (H) The derived time–intensity curve indicated a sudden echo intensity decrease during MBD and a gradual ascending recovery.Abbreviations: MBSDF-1, stromal cell-derived factor-1-loaded microbubbles; MBD, microbubble destruction; MBs, microbubbles.
© Copyright Policy
Related In: Results  -  Collection

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

f4-ijn-9-5639: In vivo imaging and ultrasound-targeted microbubble destruction.Notes: (A) At a low mechanical index, the renal parenchyma apparently improved after MBSDF-1 infusion, compared with adjacent tissues. After 4 seconds of MBD at a high mechanical index (B), the MBs in the renal parenchyma almost disappeared, showing a low acoustic intensity (C). (D–F) Within 3–4 seconds, the MBs gradually replenished until complete recovery. (G) The rectangular region of interest was positioned in the renal parenchyma (red) and the adjacent tissue at the same depth (blue). (H) The derived time–intensity curve indicated a sudden echo intensity decrease during MBD and a gradual ascending recovery.Abbreviations: MBSDF-1, stromal cell-derived factor-1-loaded microbubbles; MBD, microbubble destruction; MBs, microbubbles.
Mentions: After MBSDF-1 infusion, the echogenicity of renal parenchyma was markedly enhanced, with an explicit border at a low MI of 0.05 (Figure 4A). During 4 seconds of MBD at a high MI of 1.5, the MBs were destroyed from the near acoustic field to the far acoustic field (Figure 4B). Immediately after MBD, the MBs in the parenchyma almost vanished, leaving a hypo-echoic and blurred renal outline (Figure 4C). Within 4 seconds, the circulating MBs gradually and smoothly replenished until the perfusion of renal MBs completely recovered (Figure 4C–F). The time–intensity curve obtained from contrast dynamic analysis indicated a relative hyper-echo before MBD, a sudden decrease during MBD, and a gradually increasing recovery process (Figure 4G and H).

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