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Three-Dimensional Aggregates Enhance the Therapeutic Effects of Adipose Mesenchymal Stem Cells for Ischemia-Reperfusion Induced Kidney Injury in Rats.

Zhao X, Qiu X, Zhang Y, Zhang S, Gu X, Guo H - Stem Cells Int (2015)

Bottom Line: Low engraftment of stem cells, however, limits the therapeutic effects of AdMSCs.In vitro data indicated that AdMSCs in 3D aggregates were less susceptible to oxidative and hypoxia stress induced by 200 μM peroxide and hypoxia/reoxygenation, respectively, compared with those cultured in two-dimensional (2D) monolayer.Improved grafted AdMSCs were observed in kidney injected with 3D aggregates compared with AdMSCs cultured in 2D monolayer.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210008, China ; Institute of Urology, Nanjing University, Nanjing 210093, China.

ABSTRACT
It has been shown that administration of adipose derived mesenchymal stem cells (AdMSCs) enhanced structural and functional recovery of renal ischemia-reperfusion (IR) injury. Low engraftment of stem cells, however, limits the therapeutic effects of AdMSCs. The present study was designed to enhance the therapeutic effects of AdMSCs by delivering AdMSCs in a three-dimensional (3D) aggregates form. Microwell was used to produce 3D AdMSCs aggregates. In vitro data indicated that AdMSCs in 3D aggregates were less susceptible to oxidative and hypoxia stress induced by 200 μM peroxide and hypoxia/reoxygenation, respectively, compared with those cultured in two-dimensional (2D) monolayer. Furthermore, AdMSCs in 3D aggregates secreted more proangiogenic factors than those cultured in 2D monolayer. 2D AdMSCs or 3D AdMSCs aggregates were injected into renal cortex immediately after induction of renal IR injury. In vivo data revealed that 3D aggregates enhanced the effects of AdMSCs in recovering function and structure after renal IR injury. Improved grafted AdMSCs were observed in kidney injected with 3D aggregates compared with AdMSCs cultured in 2D monolayer. Our results demonstrated that 3D AdMSCs aggregated produced by microwell enhanced the retention and therapeutic effects of AdMSCs for renal IR injury.

No MeSH data available.


Related in: MedlinePlus

3D aggregates decrease the susceptibility of AdMSCs to stress and enhance the expression of proangiogenic factors in AdMSCs. (a) Representative FDA/PI stained images of 2D AdMSCs or 3D aggregates subjected to hypoxia/reoxygenation or 200 μM-H2O2 treatment. (b) Quantification of dead cells in 2D AdMSCs or 3D aggregates subjected to hypoxia/reoxygenation treatment using PI/FDA ratio. Data were normalized to the vehicle group of 2D monolayer culture. (c) Quantification of dead cells in 2D AdMSCs or 3D aggregates subjected to 200 μM-H2O2 treatment using PI/FDA ratio. Data were normalized to the vehicle group of 2D monolayer culture. (d) Relative mRNA expression of VEGF, FGF2, and HGF in 2D AdMSCs and 3D aggregates. ∗P < 0.05 compared with 2D AdMSCs.
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fig3: 3D aggregates decrease the susceptibility of AdMSCs to stress and enhance the expression of proangiogenic factors in AdMSCs. (a) Representative FDA/PI stained images of 2D AdMSCs or 3D aggregates subjected to hypoxia/reoxygenation or 200 μM-H2O2 treatment. (b) Quantification of dead cells in 2D AdMSCs or 3D aggregates subjected to hypoxia/reoxygenation treatment using PI/FDA ratio. Data were normalized to the vehicle group of 2D monolayer culture. (c) Quantification of dead cells in 2D AdMSCs or 3D aggregates subjected to 200 μM-H2O2 treatment using PI/FDA ratio. Data were normalized to the vehicle group of 2D monolayer culture. (d) Relative mRNA expression of VEGF, FGF2, and HGF in 2D AdMSCs and 3D aggregates. ∗P < 0.05 compared with 2D AdMSCs.

Mentions: To verify that cells in 3D aggregates enhance protection against hypoxia, AdMSCs in either 2D monolayer culture or 3D aggregates were subjected to 24 h of hypoxia followed by 2 h reoxygenation. As shown in Figures 3(a) and 3(b), cells grown in 3D aggregates were less susceptible to hypoxia/reoxygenation-induced stress compared to those cultured in 2D monolayer as determined by PI/FDA ratio. In addition, we examined the response of 2D AdMSCs or 3D aggregates to oxidative stress mimicked by 200 μM H2O2. Similar to results obtained following hypoxia/reoxygenation, reduced cell death, as determined by PI/FDA, was observed in 3D aggregates (Figures 3(a) and 3(c)).


Three-Dimensional Aggregates Enhance the Therapeutic Effects of Adipose Mesenchymal Stem Cells for Ischemia-Reperfusion Induced Kidney Injury in Rats.

Zhao X, Qiu X, Zhang Y, Zhang S, Gu X, Guo H - Stem Cells Int (2015)

3D aggregates decrease the susceptibility of AdMSCs to stress and enhance the expression of proangiogenic factors in AdMSCs. (a) Representative FDA/PI stained images of 2D AdMSCs or 3D aggregates subjected to hypoxia/reoxygenation or 200 μM-H2O2 treatment. (b) Quantification of dead cells in 2D AdMSCs or 3D aggregates subjected to hypoxia/reoxygenation treatment using PI/FDA ratio. Data were normalized to the vehicle group of 2D monolayer culture. (c) Quantification of dead cells in 2D AdMSCs or 3D aggregates subjected to 200 μM-H2O2 treatment using PI/FDA ratio. Data were normalized to the vehicle group of 2D monolayer culture. (d) Relative mRNA expression of VEGF, FGF2, and HGF in 2D AdMSCs and 3D aggregates. ∗P < 0.05 compared with 2D AdMSCs.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig3: 3D aggregates decrease the susceptibility of AdMSCs to stress and enhance the expression of proangiogenic factors in AdMSCs. (a) Representative FDA/PI stained images of 2D AdMSCs or 3D aggregates subjected to hypoxia/reoxygenation or 200 μM-H2O2 treatment. (b) Quantification of dead cells in 2D AdMSCs or 3D aggregates subjected to hypoxia/reoxygenation treatment using PI/FDA ratio. Data were normalized to the vehicle group of 2D monolayer culture. (c) Quantification of dead cells in 2D AdMSCs or 3D aggregates subjected to 200 μM-H2O2 treatment using PI/FDA ratio. Data were normalized to the vehicle group of 2D monolayer culture. (d) Relative mRNA expression of VEGF, FGF2, and HGF in 2D AdMSCs and 3D aggregates. ∗P < 0.05 compared with 2D AdMSCs.
Mentions: To verify that cells in 3D aggregates enhance protection against hypoxia, AdMSCs in either 2D monolayer culture or 3D aggregates were subjected to 24 h of hypoxia followed by 2 h reoxygenation. As shown in Figures 3(a) and 3(b), cells grown in 3D aggregates were less susceptible to hypoxia/reoxygenation-induced stress compared to those cultured in 2D monolayer as determined by PI/FDA ratio. In addition, we examined the response of 2D AdMSCs or 3D aggregates to oxidative stress mimicked by 200 μM H2O2. Similar to results obtained following hypoxia/reoxygenation, reduced cell death, as determined by PI/FDA, was observed in 3D aggregates (Figures 3(a) and 3(c)).

Bottom Line: Low engraftment of stem cells, however, limits the therapeutic effects of AdMSCs.In vitro data indicated that AdMSCs in 3D aggregates were less susceptible to oxidative and hypoxia stress induced by 200 μM peroxide and hypoxia/reoxygenation, respectively, compared with those cultured in two-dimensional (2D) monolayer.Improved grafted AdMSCs were observed in kidney injected with 3D aggregates compared with AdMSCs cultured in 2D monolayer.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210008, China ; Institute of Urology, Nanjing University, Nanjing 210093, China.

ABSTRACT
It has been shown that administration of adipose derived mesenchymal stem cells (AdMSCs) enhanced structural and functional recovery of renal ischemia-reperfusion (IR) injury. Low engraftment of stem cells, however, limits the therapeutic effects of AdMSCs. The present study was designed to enhance the therapeutic effects of AdMSCs by delivering AdMSCs in a three-dimensional (3D) aggregates form. Microwell was used to produce 3D AdMSCs aggregates. In vitro data indicated that AdMSCs in 3D aggregates were less susceptible to oxidative and hypoxia stress induced by 200 μM peroxide and hypoxia/reoxygenation, respectively, compared with those cultured in two-dimensional (2D) monolayer. Furthermore, AdMSCs in 3D aggregates secreted more proangiogenic factors than those cultured in 2D monolayer. 2D AdMSCs or 3D AdMSCs aggregates were injected into renal cortex immediately after induction of renal IR injury. In vivo data revealed that 3D aggregates enhanced the effects of AdMSCs in recovering function and structure after renal IR injury. Improved grafted AdMSCs were observed in kidney injected with 3D aggregates compared with AdMSCs cultured in 2D monolayer. Our results demonstrated that 3D AdMSCs aggregated produced by microwell enhanced the retention and therapeutic effects of AdMSCs for renal IR injury.

No MeSH data available.


Related in: MedlinePlus