Human Adipose Tissue Derived Pericytes Increase Life Span in Utrn(tm1Ked) Dmd(mdx)/J Mice

Human Adipose Tissue Derived Pericytes Increase Life Span in Utrn(tm1Ked) Dmd(mdx)/J Mice

Author Valadares, M. C. Google Scholar
Gomes, J. P. Google Scholar
Castello, G. Google Scholar
Assoni, A. Google Scholar
Pellati, M. Google Scholar
Bueno, C. Google Scholar
Corselli, M. Google Scholar
Silva, H. Autor UNIFESP Google Scholar
Bartolini, P. Google Scholar
Vainzof, M. Google Scholar
Margarido, P. F. Google Scholar
Baracat, E. Google Scholar
Peault, B. Google Scholar
Zatz, M. Google Scholar
Institution Universidade de São Paulo (USP)
Univ Calif Los Angeles
Orthoped Hosp
Universidade Federal de São Paulo (UNIFESP)
Natl Nucl Energy Commiss IPEN CNEN
Abstract Duchenne muscular dystrophy (DMD) is still an untreatable lethal X-linked disorder, which affects 1 in 3500 male births. It is caused by the absence of muscle dystrophin due to mutations in the dystrophin gene. the potential regenerative capacity as well as immune privileged properties of mesenchymal Stem Cells (MSC) has been under investigation for many years in an attempt to treat DMD. One of the questions to be addressed is whether stem cells from distinct sources have comparable clinical effects when injected in murine or canine muscular dystrophy animal models. Many studies comparing different stem cells from various sources were reported but these cells were obtained from different donors and thus with different genetic backgrounds. Here we investigated whether human pericytes obtained from 4 different tissues (muscle, adipose tissue, fallopian tube and endometrium) from the same donor have a similar clinical impact when injected in double mutant Utrn(tm1Ked) Dmd(mdx)/J mice, a clinically relevant model for DMD. After a weekly regimen of intraperitoneal injections of 106 cells per 8 weeks we evaluated the motor ability as well as the life span of the treated mice as compared to controls. Our experiment showed that only adipose tissue derived pericytes are able to increase significantly (39 days on average) the life span of affected mice. Microarray analysis showed an inhibition of the interferon pathway by adipose derived pericytes. Our results suggest that the clinical benefit associated with intraperitoneal injections of these adult stem cells is related to immune modulation rather than tissue regeneration.
Keywords Pericytes
Stem Cells
DMD
Life Span
Adipose Tissue
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
INCT
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Date 2014-12-01
Published in Stem Cell Reviews and Reports. Totowa: Humana Press Inc, v. 10, n. 6, p. 830-840, 2014.
ISSN 1550-8943 (Sherpa/Romeo, impact factor)
Publisher Humana Press Inc
Extent 830-840
Origin http://dx.doi.org/10.1007/s12015-014-9537-9
Access rights Closed access
Type Article
Web of Science ID WOS:000344868600008
URI http://repositorio.unifesp.br/handle/11600/38503

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