Transplantation of SNAP-treated adipose tissue-derived stem cells improves cardiac function and induces neovascularization after myocardium infarct in rats.
Stem cell therapy has been considered a promise for damaged myocardial tissue. We have previously shown that S-nitroso-N-acetyl-D,L-penicillamine (SNAP) increases the expression of several muscular markers and VEGF in mesenchymal stem cells, indicating that transplantation of SNAP-treated cells could provide better functional outcomes. Here, we transplanted SNAP-treated adipose tissue-derived stem cells (ADSCs) in rat infarcted myocardium. After 30days, we observed a significant improvement of the ejection fraction in rats that received SNAP-treated ADSCs, compared with those that received untreated cells (p=0.008). Immunohistochemical reactions showed an increased expression of troponin T-C and von Willebrand factor, and organized vascular units in the infarcted area of tissue transplanted with treated ADSCs. SNAP exposure induced intracellular S-nitrosation, a decreased GSH/GSSG ratio, but did not increase cGMP levels. Collectively, these results indicate that SNAP alters the redox environment of ADSCs, possibly associated with a pre-differentiation state, which may improve cardiac function after transplantation.
Núcleo de Tecnologia Celular Pontifícia Universidade Católica do Paraná, Rua Imaculada Conceição 1155, Curitiba 80215-901, Brazil.
Gel R M
GR
Berardi
Carmen K
CK
Rebelatto
Heloísa F
HF
Tavares
Max
M
Ingberman
Patrícia
P
Shigunov
Fabiane
F
Barchiki
Alessandra M
AM
Aguiar
Nelson I
NI
Miyague
Julio C
JC
Francisco
Alejandro
A
Correa
Alexandra C
AC
Senegaglia
Paula Hansen
PH
Suss
José A
JA
Moutinho
Vanessa S
VS
Sotomaior
Lia S
LS
Nakao
Paulo S
PS
Brofman
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D005978:Glutathione / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006334:Heart Function Tests / Q000187:drug effects; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D015538:Nitrosation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013318:Stroke Volume / Q000187:drug effects; D014336:Troponin / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
D014336:Troponin; D014841:von Willebrand Factor; D049452:Green Fluorescent Proteins; D026423:S-Nitroso-N-Acetylpenicillamine; D005978:Glutathione