Adipose Tissue-Derived Stem Cell Treatment Prevents Renal Disease Progression


Autoria(s): Donizetti-Oliveira, Cassiano; Kuriki, Patricia Semedo; Silva, Marina Burgos da; Cenedeze, Marco Antonio; Malheiros, Denise Maria Avancini Costa; Reis, Marlene Antonia dos; Filho, Álvaro Pacheco e Silva; Câmara, Niels Olsen Saraiva
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

29/10/2013

29/10/2013

2012

Resumo

Adipose tissue-derived stem cells (ASCs) are an attractive source of stem cells with regenerative properties that are similar to those of bone marrow stem cells. Here, we analyze the role of ASCs in reducing the progression of kidney fibrosis. Progressive renal fibrosis was achieved by unilateral clamping of the renal pedicle in mice for 1 h; after that, the kidney was reperfused immediately. Four hours after the surgery, 2 x 10(5) ASCs were intraperitoneally administered, and mice were followed for 24 h posttreatment and then at some other time interval for the next 6 weeks. Also, animals were treated with 2 x 10(5) ASCs at 6 weeks after reperfusion and sacrificed 4 weeks later to study their effect when interstitial fibrosis is already present. At 24 h after reperfusion, ASC-treated animals showed reduced renal dysfunction and enhanced regenerative tubular processes. Renal mRNA expression of IL-6 and TNF was decreased in ASC-treated animals, whereas IL-4. IL-10, and HO-1 expression increased despite a lack of ASCs in the kidneys as determined by SRY analysis. As expected, untreated kidneys shrank at 6 weeks, whereas the kidneys of ASC-treated animals remained normal in size, showed less collagen deposition, and decreased staining for FSP-1, type I collagen, and Hypoxyprobe. The renal protection seen in ASC-treated animals was followed by reduced serum levels of TNF-alpha, KC, RANTES, and IL-1 alpha. Surprisingly, treatment with ASCs at 6 weeks, when animals already showed installed fibrosis, demonstrated amelioration of functional parameters, with less tissue fibrosis observed and reduced mRNA expression of type I collagen and vimentin. ASC therapy can improve functional parameters and reduce progression of renal fibrosis at early and later times after injury, mostly due to early modulation of the inflammatory response and to less hypoxia, thereby reducing the epithelial-mesenchymal transition.

Brazilian Foundation-FAPESP (Fundacao de Apoio a Pesquisa do Estado de Sao Paulo) [09/13251-6, 07/07139-3]

Brazilian Foundation FAPESP (Fundacao de Apoio a Pesquisa do Estado de Sao Paulo)

CNPq [473844/2009-5]

CNPq

DECIT/Ministerio do Saude

DECIT/Ministerio do Saude

Complex Fluids INCT

Complex Fluids INCT

Identificador

CELL TRANSPLANTATION, PUTNAM VALLEY, v. 21, n. 8, supl. 4, Part 1-2, pp. 1727-1741, OCT 24, 2012

0963-6897

http://www.producao.usp.br/handle/BDPI/36501

10.3727/096368911X623925

http://dx.doi.org/10.3727/096368911X623925

Idioma(s)

eng

Publicador

COGNIZANT COMMUNICATION CORP

PUTNAM VALLEY

Relação

CELL TRANSPLANTATION

Direitos

closedAccess

Copyright COGNIZANT COMMUNICATION CORP

Palavras-Chave #ADIPOSE-DERIVED STEM CELL #ACUTE KIDNEY INJURY #ISCHEMIA-REPERFUSION INJURY #FIBROSIS #INFLAMMATION #EPITHELIAL-MESENCHYMAL TRANSITION #ACUTE KIDNEY INJURY #NF-KAPPA-B #STROMAL CELLS #NITRIC-OXIDE #MYOCARDIAL-INFARCTION #FIBROSIS #INFLAMMATION #MECHANISMS #FAILURE #CELL & TISSUE ENGINEERING #MEDICINE, RESEARCH & EXPERIMENTAL #TRANSPLANTATION
Tipo

article

original article

publishedVersion