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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

2D AdMSCs or 3D aggregate preserves renal function and histology after IR. ((a)-(b)) Circulating levels of urea nitrogen (BUN) and creatinine (Cr) in different experimental groups (n = 6 in each group). (c) Representative images of HE staining of kidney sections in each experimental group, showing significantly higher degree of tubular damage including tubular necrosis, cast formation, dilatation of tubules, and loss of brush border in IR group. (d) Results of total histopathological scores reflecting tubular damage in each group. ∗P < 0.05.
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fig4: 2D AdMSCs or 3D aggregate preserves renal function and histology after IR. ((a)-(b)) Circulating levels of urea nitrogen (BUN) and creatinine (Cr) in different experimental groups (n = 6 in each group). (c) Representative images of HE staining of kidney sections in each experimental group, showing significantly higher degree of tubular damage including tubular necrosis, cast formation, dilatation of tubules, and loss of brush border in IR group. (d) Results of total histopathological scores reflecting tubular damage in each group. ∗P < 0.05.

Mentions: Serum levels of BUN and Cr were selected to determine the renal function. As shown in Figures 4(a) and 4(b), both BUN and Cr levels were significantly higher in IR group than sham group. Injection of AdMSCs, either 2D monolayer culture or 3D aggregates, showed positive effects in preserving renal function, reflected by significantly reduced BUN and Cr levels compared to the IR group. More importantly, the levels of BUN and Cr in IR + aggregates group were significantly lower compared with those in 2D AdMSCs group. These findings implicated that 3D aggregates showed significantly improved protective effects compared with 2D AdMSCs.


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)

2D AdMSCs or 3D aggregate preserves renal function and histology after IR. ((a)-(b)) Circulating levels of urea nitrogen (BUN) and creatinine (Cr) in different experimental groups (n = 6 in each group). (c) Representative images of HE staining of kidney sections in each experimental group, showing significantly higher degree of tubular damage including tubular necrosis, cast formation, dilatation of tubules, and loss of brush border in IR group. (d) Results of total histopathological scores reflecting tubular damage in each group. ∗P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4663369&req=5

fig4: 2D AdMSCs or 3D aggregate preserves renal function and histology after IR. ((a)-(b)) Circulating levels of urea nitrogen (BUN) and creatinine (Cr) in different experimental groups (n = 6 in each group). (c) Representative images of HE staining of kidney sections in each experimental group, showing significantly higher degree of tubular damage including tubular necrosis, cast formation, dilatation of tubules, and loss of brush border in IR group. (d) Results of total histopathological scores reflecting tubular damage in each group. ∗P < 0.05.
Mentions: Serum levels of BUN and Cr were selected to determine the renal function. As shown in Figures 4(a) and 4(b), both BUN and Cr levels were significantly higher in IR group than sham group. Injection of AdMSCs, either 2D monolayer culture or 3D aggregates, showed positive effects in preserving renal function, reflected by significantly reduced BUN and Cr levels compared to the IR group. More importantly, the levels of BUN and Cr in IR + aggregates group were significantly lower compared with those in 2D AdMSCs group. These findings implicated that 3D aggregates showed significantly improved protective effects compared with 2D AdMSCs.

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