Abstract 16038: Bone Marrow SSEA1+ Cells Contribute in the Response to Cardiac Pressure Overload
Introduction: SSEA1+ cells have been described as the most primitive mesenchymal progenitor cell in the bone marrow (BM). We have observed a significant proliferative response of SSEA1+ in response to pressure overload (PO) but their role in response to cardiac injury remains to be defined.
Methods and Results: Lethally irradiated mice were transplanted with normal bone marrow in which the wild-type SSEA1+ were replaced with GFP+ SSEA1+. PO was induced by trans-aortic constriction (TAC). The fate of GFP+ cells was determined in the BM, spleen, and heart by flow cytometry 1 w post-TAC. Mice were also transplanted with either total GFP BM or GFP BM depleted of SSEA1+ cells. TAC and Sham operations were performed and cardiac function was assessed by echocardiography. Consistent with the proliferative response of SSEA1+ following PO, we observed a 66.8% increase of GFP+ cells in the BM 1 w after TAC. However, this increase did not correlate with an increase in SSEA1+ cells. GFP+ hematopoietic stem cell (HSC) and endothelial progenitor cell (EPC) were observed in Sham (7 weeks post-transplant) in the BM and spleen, with GFP contribution increasing after TAC (BM - HSC 1.9% vs 10.92 %, EPC 9.3% vs 32.3%; spleen - HSC 1.5% vs 6.8%, EPC 2.4% vs 10.5%). Similarly, in the heart, there was an increase in the percentage of GFP+ EPC after TAC (Sham 1.6% vs TAC 9%). Interestingly, we observed minimal contribution of GFP+ cells to the cardiac stem cell population (Sham 0% vs TAC 0.5%). Mice with SSEA1 depleted BM had normal cardiac function and normal blood cell counts at baseline compared to total BM transplanted mice. However, in response to TAC, mice with SSEA1+ depleted BM had a reduced cardiac function in response to TAC resulting in decreased ejection fraction (SSEA1 depleted -19.4±2.1%, total GFP BM -6.1±0.7% percent change in EF compared to sham, p=0.04) 2 weeks post TAC.
Conclusions: Our results demonstrate for the first time, in vivo, the natural fate of BM SSEA1+ cells to become cells of hematopoietic and endothelial origin. We also have determined that BM SSEA1+ deficiency results in a reduced compensatory capacity in response to pressure overload. Further studies are in progress understand the mechanism in which SSEA1+ cells support the myocardium in response to TAC
- © 2011 by American Heart Association, Inc.