Abstract 793: The Role of akt-1 and Hematopoietic Stem Cells in Amelioration of Myocardial Function Following Myocardial Infarction
Background: The transplantation of hematopoietic stem cells (HSC) has been proposed as a strategy for cardiac repair and prevention of cardiac remodeling in dameged hearts. We assessed if Akt-1 was important in HSC dependent amelioration of myocardial performance in infarcted myocardium.
Objective: Our goal was to compare the effects of wild type and Akt1 deficient (Akt1−/−) HSC, delivered to injured heart using targeting strategy, on cardiac function and remodeling.
Methods: Bone marrow from wild type and Akt1−/− mice was collected from tibias femurs and iliac crests. Lin−-c-kit+ HSC was sorted by magnetic cell sorting using a MACS separator. A “bi-antibody” heteroconjugate of anti-c-kit x anti-VCAM-1 antibodies was used to “arm” HSC to increase cell homing. SCID mice were used as recipients. Myocardial infarction (MI) was created by ligation of the left anterior descending artery. After 48 hours, mice were given ‘armed’ HSC by tail vein injection and divided into 4 groups:
Sham: underwent thoractomy without MI;
MI: received cell culture medium;
MI + wt: received 5x105 wild type HSC;
MI + Akt-1−/− : received 5x105 Akt-1−/− HSC.
Two weeks after HSC administration, cardiac function was measured in Langendorff mode. Cardiac morphology was examined by H&E, Masson trichrome stainings.
Results: Administration of wild type HSC to SCID mice with infarcted hearts significantly increased the recovery of left ventricular systolic pressure (LVSP), left ventricular developed pressure (LVDP) and LV dp/dt as compared to mice in the MI group (p<0.05). These improvements were eliminated in mice who received Akt-1−/−HSC cells. H&E staining demonstrated that MI + wt hearts had smaller infarctions relative to MI + Akt-1−/− hearts. Masson staining showed less fibrosis in the MI + wt hearts as compared to MI + Akt-1−/− hearts.
Conclusion: Akt-1 plays an essential role in the hematopoietic stem cell dependent amelioration of myocardial function following myocardial infarction.