Limits...
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.

Show MeSH

Related in: MedlinePlus

Determination of bioactivity by cell migration assay.Notes: (A) Determination of bioactivity based on a cell migration assay. The number of migrated MSCs increased in the SDF-1 group and the MBSDF-1 group compared with the control group. Preincubation with AMD3100 inhibited the migration. The white bars in (A) indicate 200 μm. (B) The histogram of the number of migrated cells in each group. The asterisk indicates a significant difference compared to the control group; *P<0.05 (P-value of 9.99×10−15, SDF-1 versus control; P value of 3.66×10−14, MBSDF-1 versus control). The hash symbol indicates a significant difference compared to the same treatment without AMD3100; #P<0.05 (P-value of 5.00×10−7, SDF-1 + AMD3100 versus control + AMD3100; P-value of 1.92×10−5, MBSDF-1 + AMD3100 versus control + AMD3100).Abbreviations: MSCs, mesenchymal stem cells; SDF-1, stromal cell-derived factor-1; MBSDF-1, SDF-1-loaded microbubbles.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4263441&req=5

f3-ijn-9-5639: Determination of bioactivity by cell migration assay.Notes: (A) Determination of bioactivity based on a cell migration assay. The number of migrated MSCs increased in the SDF-1 group and the MBSDF-1 group compared with the control group. Preincubation with AMD3100 inhibited the migration. The white bars in (A) indicate 200 μm. (B) The histogram of the number of migrated cells in each group. The asterisk indicates a significant difference compared to the control group; *P<0.05 (P-value of 9.99×10−15, SDF-1 versus control; P value of 3.66×10−14, MBSDF-1 versus control). The hash symbol indicates a significant difference compared to the same treatment without AMD3100; #P<0.05 (P-value of 5.00×10−7, SDF-1 + AMD3100 versus control + AMD3100; P-value of 1.92×10−5, MBSDF-1 + AMD3100 versus control + AMD3100).Abbreviations: MSCs, mesenchymal stem cells; SDF-1, stromal cell-derived factor-1; MBSDF-1, SDF-1-loaded microbubbles.

Mentions: A remarkable number of MSCs migrated in the SDF-1 group and the MBSDF-1 group compared with the control group. The number of migrated MSCs did not significantly differ between the MBSDF-1 group and the SDF-1 group (Figure 3A). After blocking CXCR4 with AMD3100, the migrated cells in the SDF-1 + AMD3100 group and the MBSDF-1 + AMD3100 group decreased compared with those in the SDF-1 group and the MBSDF-1 group, respectively (Figure 3A and B).


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)

Determination of bioactivity by cell migration assay.Notes: (A) Determination of bioactivity based on a cell migration assay. The number of migrated MSCs increased in the SDF-1 group and the MBSDF-1 group compared with the control group. Preincubation with AMD3100 inhibited the migration. The white bars in (A) indicate 200 μm. (B) The histogram of the number of migrated cells in each group. The asterisk indicates a significant difference compared to the control group; *P<0.05 (P-value of 9.99×10−15, SDF-1 versus control; P value of 3.66×10−14, MBSDF-1 versus control). The hash symbol indicates a significant difference compared to the same treatment without AMD3100; #P<0.05 (P-value of 5.00×10−7, SDF-1 + AMD3100 versus control + AMD3100; P-value of 1.92×10−5, MBSDF-1 + AMD3100 versus control + AMD3100).Abbreviations: MSCs, mesenchymal stem cells; SDF-1, stromal cell-derived factor-1; MBSDF-1, SDF-1-loaded microbubbles.
© Copyright Policy
Related In: Results  -  Collection

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

f3-ijn-9-5639: Determination of bioactivity by cell migration assay.Notes: (A) Determination of bioactivity based on a cell migration assay. The number of migrated MSCs increased in the SDF-1 group and the MBSDF-1 group compared with the control group. Preincubation with AMD3100 inhibited the migration. The white bars in (A) indicate 200 μm. (B) The histogram of the number of migrated cells in each group. The asterisk indicates a significant difference compared to the control group; *P<0.05 (P-value of 9.99×10−15, SDF-1 versus control; P value of 3.66×10−14, MBSDF-1 versus control). The hash symbol indicates a significant difference compared to the same treatment without AMD3100; #P<0.05 (P-value of 5.00×10−7, SDF-1 + AMD3100 versus control + AMD3100; P-value of 1.92×10−5, MBSDF-1 + AMD3100 versus control + AMD3100).Abbreviations: MSCs, mesenchymal stem cells; SDF-1, stromal cell-derived factor-1; MBSDF-1, SDF-1-loaded microbubbles.
Mentions: A remarkable number of MSCs migrated in the SDF-1 group and the MBSDF-1 group compared with the control group. The number of migrated MSCs did not significantly differ between the MBSDF-1 group and the SDF-1 group (Figure 3A). After blocking CXCR4 with AMD3100, the migrated cells in the SDF-1 + AMD3100 group and the MBSDF-1 + AMD3100 group decreased compared with those in the SDF-1 group and the MBSDF-1 group, respectively (Figure 3A and B).

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