Rat Adipose Tissue-Derived Stem Cells Transplantation Attenuates Cardiac Dysfunction Post Infarction and Biopolymers Enhance Cell Retention

Autor(es)

Danoviz, Maria E. ^[1] ; Nakamuta, Juliana S. ^[1] ; Marques, Fabio L. N. ^[2] ; dos Santos, Leonardo ^[1] ; Alvarenga, Erica C. ^[3] ; dos Santos, Alexandra A. ^[4] ; Antonio, Ednei L. ^[4] ; Schettert, Isolmar T. ^[1] ; Tucci, Paulo J. ^[4] ; Krieger, Jose E. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Inst Heart, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Nucl Med Ctr, Radiopharm Lab, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Biophys, Sao Paulo - Brazil

^[4] Univ Fed Sao Paulo, Div Cardiol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 5, n. 8, p. e12077, 2010.
• Citações Web of Science: 68

Resumo

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). Methodology/Principal Findings: Tc-99m-labeled ASCs (1 x 10(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 administrating co-injection of ASCs with biopolymers. (AU)

• Processo FAPESP: 04/06784-4 - Capacidade de transdiferenciação das células mesenquimais do tecido adiposo: estudo no reparo cardiovascular
• Beneficiário: Juliana Sanajotti Nakamuta
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 05/54695-3 - Reparação cardíaca biológica pós-infarto: uso de células tronco derivadas do tecido adiposo, isoladas ou associadas a fibroblastos a fibroblastos geneticamente modificados para produzir VEGF
• Beneficiário: Maria Elena Danoviz
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto