Bone marrow-derived mononuclear cell therapy alleviates left ventricular remodeling and improves heart function in rat-dilated cardiomyopathy.
OBJECTIVE
This study hypothesized that bone marrow-derived mononuclear cell (BMDMNC) therapy may improve cardiac function through preventing cell death, alleviating left ventricular (LV) remodeling, and enhancing angio-/vasculo-genesis, as well as preserving LV contractility in a rat model of dilated cardiomyopathy (DCM).


METHODS
A model of DCM in Sprague-Dawley rats was used to investigate the effects of BMDMNC therapy on inflammatory and oxidative response, energy depression, cellular apoptosis, expressions of protein kinase C-(PKC)-epsilon, and connexin43 protein (Cx43) in LV myocardium and heart function.


METHODS
An animal model research laboratory at Kaohsiung Chang Gung Memorial Hospital.


METHODS
The rats were divided into group 1 (normal control, n = 8), group 2 (saline-treated DCM, n = 10), and group 3 (1.2 x 10 BMDMNC implanted into LV anterior wall on day 35 after DCM induction, n = 10). The DCM and normal control rats were killed on day 90 following DCM induction.


RESULTS
The results demonstrated that Cx43 protein expression and messenger RNA expressions of peroxisome proliferator-activated receptor-gamma coactivator 1 alpha, endothelial nitric oxide synthase, and interleukin-10 were higher, whereas messenger RNA expressions of endothelin-1 and matrix metalloproteinase-9 were lower in groups 1 and 3 than in group 2 (all p < 0.05). Additionally, expressions of PKC-epsilon in plasma membrane and mitochondria and LV function were conserved in group 1 and improved in group 3, whereas cardiomyocyte apoptosis, mitochondrial oxidative stress, and fibrosis of LV myocardium were reduced in groups 1 and 3 than in group 2 (all p < 0.005).


CONCLUSIONS
BMDMNC therapy in DCM significantly improves LV function by limiting cellular apoptosis, inflammatory and oxidative responses, and by up-regulating expressions of Cx43, PKC-epsilon, and energy transcription factors.
Sun
Cheuk-Kwan
CK
Division of General Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Republic of China.
Chang
Li-Teh
LT
Sheu
Jiunn-Jye
JJ
Chiang
Chiang-Hua
CH
Lee
Fan-Yen
FY
Wu
Chiung-Jen
CJ
Chua
Sarah
S
Fu
Morgan
M
Yip
Hon-Kan
HK
D000818:Animals; D016026:Bone Marrow Transplantation; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology* / Q000601:surgery*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020257:Ventricular Remodeling