Abstract 1074: Bone Marrow-derived CD31+ Cells have Angiogenic-vasculogenic Properties and are Effective for Repairing Ischemic Cardiovascular Diseases
Background: CD31, PECAM-1 has been used as a marker for endothelial cells. However, recent data have indicated that CD31 is also expressed at an early developmental stage. We hypothesized that CD31 could serve as a comprehensive epitope to encircle various subsets of hemangioblastic cells in adult bone marrow (BM).
Methods and Results: A fraction of CD31+ cells of BM mononuclear cells in C57BL/6 mice co-expressed well known stem cell markers including c-kit, Sca-1, and flk-1. The expression levels of these markers were distinct when hematopoietic lineage positive cells were depleted (Lin−) from CD31+ cells. Moreover, Lin−CD31+ cells exclusively expressed genes characterizing pluripotency such as Oct4, Rex4, Nanog, and SSEA-1.A microarray revealed that CD31+ cells expressed multiple angiogenic genes compared to CD31− cells. In particular, only a CD31+ but not CD31− fraction gave rise to endothelial progenitor cells (EPCs) in a culture assay. To determine in vivo activity, we performed BM repopulating experiments. All mice transplanted with 1x105 CD31+ cells survived after lethal irradiation, whereas mice with CD31− cells all died within 4 weeks (n=10, each). We then tested therapeutic efficacy of CD31+ cells. In a hindlimb ischemia model, 1x106 cells were injected intravenously, and in a myocardial infarction (MI) model, 5x105 were injected intramyocardially. After 2 weeks of limb ischemia, CD31+ cell group showed increased limb perfusion and capillary density as well as greater efficacy to salvage ischemic limbs, compared to PBS, whole BM cell and CD31− cell injected groups (n=7, each). The injected CD31+ cells preferentially assumed pericytic morphology. However, a few cells were co-localized with capillaries and myocytes. After 2 and 4 weeks of MI and cell transplantation, systolic and diastolic functions were better and fibrosis-scar size was smaller in mice receiving CD31+ cells compared to the control groups (n=5, each).
Conclusions: We demonstrated that CD31 antigen can function as a comprehensive marker to encompass most of the currently identified BM cells showing hemangioblastic activity. These findings suggest that a strategy of CD31+ cell transplantation may have significant therapeutic potential for repairing ischemic limb and heart.