Abstract 21348: Bone Marrow Multipotent Mesenchymal Stromal Cells Prolong the Survival of Cardiac Allograft in Rats
In the present study we have evaluated the effects of local delivery of donor multipotent mesenchymal stromal cells (MSCs) on the survival of transplanted neonatal hearts in a rat ear pinna allograft model. Recipient inbred Wistar-Kyoto rats were transplanted with neonatal hearts extracted from pups of outbred Wistar rats (AL-MSC, n=5). Wistar-Kyoto MSCs, extracted from bone marrow and cultured in vitro were locally delivered in ear pinna around the neonatal heart immediately after transplantation. MSCs were previously labeled with DiI-CM-celltracker. MSCs were characterized as c-Kit, CD31 and CD45 negative cells and CD29 positive cells by flow cytometer and exhibited multipotential for differentiation. Recipient Wistar-Kyoto rats, transplanted with neonatal hearts of Wistar rats, but not receiving MSCs (AL-CON, n=9), were used as allogenic control. As an isogenic control, inbred Wistar-Kyoto rats were transplanted with neonatal Wistar-Kyoto hearts (ISO, n=9). In both AL-CON and ISO groups, saline was locally administered. After heart transplantation and local cell delivery, all animals were followed during three weeks and the survival of neonatal heart was evaluated by visual inspection and electrocardiographical recordings. Hearts with irregular rhythm and heart rate lower than 05 beats per minute (bpm) were considered rejected. At the end, heart tissue, inflammatory infiltration and DiICM positive cells were histologically evaluated. After three weeks, all neonatal hearts from ISO group were viable with mean (±SEM) heart rate of 74±12bpm. Viability and mean heart rate of neonatal hearts in AL-CON group were 77.8% and 9.0±1.8bpm, 44.4% and 7.1±2.1bpm and 22.2% and 2.2±1.2bpm, respectively. In AL-MSC group, viability and mean heart rate of neonatal hearts were 100.0% (p<0.05) and 70.8±18.5bpm (p<0.01), 100.0% (p<0.05) and 30.0±17.5bpm (p<0.05) and 20.0% and 2.0±0.9bpm, respectively. Moderate inflammatory infiltration and DiI-CM positive cells around heart tissue were observed in AL-MSC animals, contrasting with marked inflammatory infiltration and absence of heart tissue in AL-CON animals. Our results indicated that local delivery of MSCs prolonged the survival of transplanted hearts, possibly by induction of allograft tolerance.
- © 2010 by American Heart Association, Inc.