Role of adipose tissue-derived stem cells in the progression of renal disease

Abstract

Objective: To analyze the role of adipose tissue-derived stem cells in reducing the progression of renal fibrosis. Methods: adipose tissue-derived stem cells were isolated from C57Bl/6 mice and characterized by cytometry and differentiation. Renal fibrosis was established after unilateral clamping of the renal pedicle for 1 hour. Four hours after reperfusion, 2.105 adipose tissue-derived stem cells were administered intraperitoneally and the animals were followed for 24 hours during 6 weeks. In another experimental group, 2.105 adipose tissue-derived stem cells were administered only after 6 weeks of reperfusion, and they were euthanized and studied 4 weeks later. Twenty-four hours after reperfusion, the animals treated with adipose tissue-derived stem cells displayed reduced renal and tubular dysfunction and an increase of the regenerative process. Renal expression of IL-6 and TNF mRNA were decreased in the animals treated with adipose tissue-derived stem cells, while the levels of IL-4, IL-10, and HO-1 were increased, despite the fact that adipose tissue-derived stem cells were not observed in the kidneys via SRY analysis. Results: In 6 weeks, the kidneys of non-treated animals decreased in size, and the kidneys of the animals treated with adipose tissue-derived stem cells remained at normal size and display less deposition of type 1 collagen and FSP-1. The renal protection observed in animals treated with adipose tissue-derived stem cells was followed by a drop in serum levels of TNF-α, KC, RANTES, and IL-1a. Treatment with adipose tissue-derived stem cells after 6 weeks, when the animals already displayed established fibrosis, demonstrated an improvement in functional parameters and less fibrosis analyzed by Picrosirius stain, as well as a reduction of the expression of type 1 collagen and vimentin mRNA. Conclusion: Treatment with adipose tissue-derived stem cells may deter the progression of renal fibrosis by modulation of the early inflammatory response, likely via reduction of the epithelial-mesenchymal transition.

Therapeutic Effects of Stem Cells From Different Source on Renal Ischemia- Reperfusion Injury: A Systematic Review and Network Meta-analysis of Animal Studies

“…There were great differences in the types and sources of stem cells. Adipose Tissue-Derived Mesenchymal Stem Cells (ADMSCs) were derived from SD rats ( Chen et al, 2011 ; Gao et al, 2012 ; Masoud et al, 2012 ; Shih et al, 2013 ; Sheashaa et al, 2016 ; Zhou et al, 2016 ; Lam et al, 2017 ; Zhang et al, 2017 ; Changizi-Ashtiyani et al, 2020 ), Wistar rats ( Wang et al, 2013 ; Hussein et al, 2016 ; Zhao et al, 2016 ; Shi et al, 2018 ; Awadalla et al, 2021 ), humans ( Zhou et al, 2017 ; Huang et al, 2020 ), Fisher 344 rats ( Feng et al, 2010 ) and C57BL/6 mice ( Donizetti-Oliveira et al, 2011 ; Donizetti-Oliveira et al, 2012 ; Furuichi et al, 2012 ). Bone Marrow Derived Mesenchymal Stem Cells (MDMSCs) were derived from Lewis rats ( Erpicum et al, 2017 ), Wister rats ( Semedo et al, 2009 ; Havakhah et al, 2018 ), SD rats ( Lange et al, 2005 ; Wang et al, 2005 ; Wang and Fu, 2008 ; Tögel et al, 2009 ; Zhuo et al, 2011 ; Altun et al, 2012 ; Huang et al, 2012 ; Zhuo et al, 2013 ; Cai et al, 2014a ; Cai et al, 2014b ; Zhao et al, 2014 ; Wang et al, 2019 ), C57BL/6 mice ( Liu et al, 2011 ; Qi et al, 2014 ; Xie et al, 2015 ; Hu et al, 2016 ), BALB/C mice ( Xing et al, 2014 ), Rabbits ( Yang et al, 2008 ; Fang, 2009 ), Sheep ( Behr et al, 2007 ; Behr et al, 2009 ) and human ( Cao et al, 2010 ; Wise et al, 2014 ; Collett et al, 2017b ; Zilberman-Itskovich et al, 2019 ).…”

“…①1 day after administration: 36 studies were included for data analysis ( Chen et al, 2011 ; Erpicum et al, 2017 ; Guo and Wang, 2018 ; Ryoun et al, 2014 ; Bo et al, 2013 ; Zhuo et al, 2013 ; Liang et al, 2015 ; Behr et al, 2009 ; Gupta et al, 2015 ; Sadek et al, 2013 ; Rodrigues et al, 2017 ; Tian et al, 2017 ; Havakhah et al, 2018 ; Behr et al, 2007 ; Cai et al, 2014b ; Zhuo et al, 2011 ; Hu et al, 2013 ; Cao et al, 2010 ; La Manna et al, 2011 ; Xing et al, 2014 ; Hussein et al, 2016 ; Awadalla et al, 2021 ; Zhou et al, 2016 ; Zhao et al, 2014 ; Chen et al, 2013 ; Donizetti-Oliveira et al, 2011 ; Fahmy et al, 2017 ; Hattori et al, 2015 ; Zhao et al, 2016 ; Tsuda et al, 2014 ; Li et al, 2015 ; Gao et al, 2012 ; Altun et al, 2012 ; Liu et al, 2011 ; Wang et al, 2005 ; Wang and Fu, 2008 ). The results of traditional meta-analysis were detailed in Table 7 , showed that blood urea nitrogen levels in different types of stem cell groups were lower than those in the negative control group.…”

“…14 studies were included for data analysis ( Behr et al, 2009 ; Cao et al, 2010 ; Donizetti-Oliveira et al, 2011 ; Liu et al, 2011 ; Donizetti-Oliveira et al, 2012 ; Gao et al, 2012 ; Lee et al, 2012 ; Sadek et al, 2013 ; Shih et al, 2013 ; Wise et al, 2014 ; Li et al, 2015 ; Zhou et al, 2016 ; Tian et al, 2017 ; Zhou et al, 2017 ). The results of traditional meta-analysis are detailed in Table 15 , showed that there was no significant difference in proliferation of resident cells between different types of stem cells and negative control group.…”

“…14 studies were included for data analysis (Behr et al, 2009;Cao et al, 2010;Donizetti-Oliveira et al, 2011;Liu et al, 2011;Donizetti-Oliveira et al, 2012;Gao et al, 2012;Lee et al, 2012;Sadek et al, 2013;Shih et al, 2013;Wise et al, 2014;Li et al, 2015;Zhou et al, 2016;Tian et al, 2017;Zhou et al, 2017).…”

Avaliação do potencial terapêutico das células c-kit+lin- derivadas do tecido renal de ratos no tratamento da doença renal crônica experimental

“…Em relação ao uso destas células mesenquimais no tratamento da DRC, estudos prévios de pesquisadores brasileiros (Alexandre et al, 2009;Cavaglieri et al, 2009;Donizetti-Oliveira et al, 2011;Noronha et al, 2011) e outros grupos internacionais (Peng et al, 2013) região onde ocorre o domínio da proteína quinase, por um sítio de resíduo de tirosina (Hubbard, 2004).…”