Rat adipose tissue-derived stem cells transplantation attenuates cardiac dysfunction post infarction and biopolymers enhance cell retention.
BACKGROUND
Cardiac cell transplantation is compromised by low cell retention and poor graft viability. Here, the effects of co-injecting adipose tissue-derived stem cells (ASCs) with biopolymers on cell cardiac retention, ventricular morphometry and performance were evaluated in a rat model of myocardial infarction (MI).


RESULTS
99mTc-labeled ASCs (1x10(6) cells) isolated from isogenic Lewis rats were injected 24 hours post-MI using fibrin a, collagen (ASC/C), or culture medium (ASC/M) as vehicle, and cell body distribution was assessed 24 hours later by gamma-emission counting of harvested organs. ASC/F and ASC/C groups retained significantly more cells in the myocardium than ASC/M (13.8+/-2.0 and 26.8+/-2.4% vs. 4.8+/-0.7%, respectively). Then, morphometric and direct cardiac functional parameters were evaluated 4 weeks post-MI cell injection. Left ventricle (LV) perimeter and percentage of interstitial collagen in the spare myocardium were significantly attenuated in all ASC-treated groups compared to the non-treated (NT) and control groups (culture medium, fibrin, or collagen alone). Direct hemodynamic assessment under pharmacological stress showed that stroke volume (SV) and left ventricle end-diastolic pressure were preserved in ASC-treated groups regardless of the vehicle used to deliver ASCs. Stroke work (SW), a global index of cardiac function, improved in ASC/M while it normalized when biopolymers were co-injected with ASCs. A positive correlation was observed between cardiac ASCs retention and preservation of SV and improvement in SW post-MI under hemodynamic stress.


CONCLUSIONS
We provided direct evidence that intramyocardial injection of ASCs mitigates the negative cardiac remodeling and preserves ventricular function post-MI in rats and these beneficial effects can be further enhanced by administering co-injection of ASCs with biopolymers.
Danoviz
Maria E
ME
Heart Institute, University of São Paulo Medical School, São Paulo, Brazil.
Nakamuta
Juliana S
JS
Marques
Fabio L N
FL
dos Santos
Leonardo
L
Alvarenga
Erica C
EC
dos Santos
Alexandra A
AA
Antonio
Ednei L
EL
Schettert
Isolmar T
IT
Tucci
Paulo J
PJ
Krieger
Jose E
JE
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D001704:Biopolymers / Q000008:administration & dosage / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005337:Fibrin / Q000008:administration & dosage / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D007267:Injections; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D001704:Biopolymers; D005337:Fibrin; D003094:Collagen