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Adipose Tissue-Derived Stem Cells Reduce Acute and Chronic Kidney Damage in Mice.

Burgos-Silva M, Semedo-Kuriki P, Donizetti-Oliveira C, Costa PB, Cenedeze MA, Hiyane MI, Pacheco-Silva A, Câmara NO - PLoS ONE (2015)

Bottom Line: Long-term analyses, 4 weeks after FA, indicated that AdSC treatment reduced kidney fibrosis and chronic inflammation.These were demonstrated by reduced interstitial collagen deposition and tissue chemokine and cytokine expression.Thus, we concluded that AdSC treatment played a protective role in the framework of nephrotoxic injury via modulation of inflammation and cell cycle regulation, resulting in reduced kidney damage and functional improvement, inhibiting organ fibrosis and providing long-term immune regulation.

View Article: PubMed Central - PubMed

Affiliation: Nephrology Division, Federal University of São Paulo, São Paulo, São Paulo, Brazil.

ABSTRACT
Acute and chronic kidney injuries (AKI and CKI) constitute syndromes responsible for a large part of renal failures, and are today still associated with high mortality rates. Given the lack of more effective therapies, there has been intense focus on the use stem cells for organ protective and regenerative effects. Mesenchymal stem cells (MSCs) have shown great potential in the treatment of various diseases of immune character, although there is still debate on its mechanism of action. Thus, for a greater understanding of the role of MSCs, we evaluated the effect of adipose tissue-derived stem cells (AdSCs) in an experimental model of nephrotoxicity induced by folic acid (FA) in FVB mice. AdSC-treated animals displayed kidney functional improvement 24h after therapy, represented by reduced serum urea after FA. These data correlated with cell cycle regulation and immune response modulation via reduced chemokine expression and reduced neutrophil infiltrate. Long-term analyses, 4 weeks after FA, indicated that AdSC treatment reduced kidney fibrosis and chronic inflammation. These were demonstrated by reduced interstitial collagen deposition and tissue chemokine and cytokine expression. Thus, we concluded that AdSC treatment played a protective role in the framework of nephrotoxic injury via modulation of inflammation and cell cycle regulation, resulting in reduced kidney damage and functional improvement, inhibiting organ fibrosis and providing long-term immune regulation.

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Stem cell characterization.AdSC from FVB mice were maintained for a maximum of 5 passages and stem cell profile was evaluated through membrane receptor phenotyping and differentiation assays. (A) Representative image of AdSC displaying cell phenotype under bright-field microscopy (original magnification: 20x). (B-D) Stem cell pluripotency was evaluated by culture adipogenesis and osteogenesis under differentiation stimuli and posterior staining with (B) Oil Red and (C) Alizarin Red or (D) Von Kossa, respectively (original magnification: 20x). (E) Representative histograms for stem cell marker expression (CD34, CD45, CD73, CD90 and CD105) obtained by cytometric analysis.
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pone.0142183.g001: Stem cell characterization.AdSC from FVB mice were maintained for a maximum of 5 passages and stem cell profile was evaluated through membrane receptor phenotyping and differentiation assays. (A) Representative image of AdSC displaying cell phenotype under bright-field microscopy (original magnification: 20x). (B-D) Stem cell pluripotency was evaluated by culture adipogenesis and osteogenesis under differentiation stimuli and posterior staining with (B) Oil Red and (C) Alizarin Red or (D) Von Kossa, respectively (original magnification: 20x). (E) Representative histograms for stem cell marker expression (CD34, CD45, CD73, CD90 and CD105) obtained by cytometric analysis.

Mentions: FVB AdSCs were initially expanded for 5 passages and later characterized by cell differentiation and immunophenotyping assays. Cultured cells displayed typical fibroblastoid morphology (Fig 1A) and under appropriate stimuli, exhibited potential for adipocyte and osteocyte differentiation demonstrated through Oil Red, Alizarin and Von Kossa staining (Fig 1B–1D). Cells also expressed characteristic stem cells markers CD73, CD105 and CD90, being negative for CD45 and CD34 (Fig 1E).


Adipose Tissue-Derived Stem Cells Reduce Acute and Chronic Kidney Damage in Mice.

Burgos-Silva M, Semedo-Kuriki P, Donizetti-Oliveira C, Costa PB, Cenedeze MA, Hiyane MI, Pacheco-Silva A, Câmara NO - PLoS ONE (2015)

Stem cell characterization.AdSC from FVB mice were maintained for a maximum of 5 passages and stem cell profile was evaluated through membrane receptor phenotyping and differentiation assays. (A) Representative image of AdSC displaying cell phenotype under bright-field microscopy (original magnification: 20x). (B-D) Stem cell pluripotency was evaluated by culture adipogenesis and osteogenesis under differentiation stimuli and posterior staining with (B) Oil Red and (C) Alizarin Red or (D) Von Kossa, respectively (original magnification: 20x). (E) Representative histograms for stem cell marker expression (CD34, CD45, CD73, CD90 and CD105) obtained by cytometric analysis.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4643882&req=5

pone.0142183.g001: Stem cell characterization.AdSC from FVB mice were maintained for a maximum of 5 passages and stem cell profile was evaluated through membrane receptor phenotyping and differentiation assays. (A) Representative image of AdSC displaying cell phenotype under bright-field microscopy (original magnification: 20x). (B-D) Stem cell pluripotency was evaluated by culture adipogenesis and osteogenesis under differentiation stimuli and posterior staining with (B) Oil Red and (C) Alizarin Red or (D) Von Kossa, respectively (original magnification: 20x). (E) Representative histograms for stem cell marker expression (CD34, CD45, CD73, CD90 and CD105) obtained by cytometric analysis.
Mentions: FVB AdSCs were initially expanded for 5 passages and later characterized by cell differentiation and immunophenotyping assays. Cultured cells displayed typical fibroblastoid morphology (Fig 1A) and under appropriate stimuli, exhibited potential for adipocyte and osteocyte differentiation demonstrated through Oil Red, Alizarin and Von Kossa staining (Fig 1B–1D). Cells also expressed characteristic stem cells markers CD73, CD105 and CD90, being negative for CD45 and CD34 (Fig 1E).

Bottom Line: Long-term analyses, 4 weeks after FA, indicated that AdSC treatment reduced kidney fibrosis and chronic inflammation.These were demonstrated by reduced interstitial collagen deposition and tissue chemokine and cytokine expression.Thus, we concluded that AdSC treatment played a protective role in the framework of nephrotoxic injury via modulation of inflammation and cell cycle regulation, resulting in reduced kidney damage and functional improvement, inhibiting organ fibrosis and providing long-term immune regulation.

View Article: PubMed Central - PubMed

Affiliation: Nephrology Division, Federal University of São Paulo, São Paulo, São Paulo, Brazil.

ABSTRACT
Acute and chronic kidney injuries (AKI and CKI) constitute syndromes responsible for a large part of renal failures, and are today still associated with high mortality rates. Given the lack of more effective therapies, there has been intense focus on the use stem cells for organ protective and regenerative effects. Mesenchymal stem cells (MSCs) have shown great potential in the treatment of various diseases of immune character, although there is still debate on its mechanism of action. Thus, for a greater understanding of the role of MSCs, we evaluated the effect of adipose tissue-derived stem cells (AdSCs) in an experimental model of nephrotoxicity induced by folic acid (FA) in FVB mice. AdSC-treated animals displayed kidney functional improvement 24h after therapy, represented by reduced serum urea after FA. These data correlated with cell cycle regulation and immune response modulation via reduced chemokine expression and reduced neutrophil infiltrate. Long-term analyses, 4 weeks after FA, indicated that AdSC treatment reduced kidney fibrosis and chronic inflammation. These were demonstrated by reduced interstitial collagen deposition and tissue chemokine and cytokine expression. Thus, we concluded that AdSC treatment played a protective role in the framework of nephrotoxic injury via modulation of inflammation and cell cycle regulation, resulting in reduced kidney damage and functional improvement, inhibiting organ fibrosis and providing long-term immune regulation.

Show MeSH
Related in: MedlinePlus