Abstract 336: Human Bone Contains Primitive Cells With Angiogenic and Immunomodulatory Properties

Abstract

Previously, we have shown that treatments of cortical bone derived stem cells (CBSCs) reduce ventricular remodeling and improve cardiac functions in both mouse and pig myocardial infarction (MI) models. The goals of the present study were to isolate and characterize human CBSCs (hCBSCs). Using bone fragments obtained at the time surgeries, we isolated three morphologically distinctive hCBSC phenotypes; 1) sphere forming (SF); 2) epithelial like monolayer (ELM); and 3) larger and spindle shaped (LSS) phenotype. The hCBSC phenotypes grew without senescence in culture. Mean doubling time (hour) for SF, ELM, and LSS at the passage number 20 (P20) were 19.54, 21.21, and 20.3 respectively and at the P40 were 18.01, 17.13, and 20.56 respectively. All of the phenotypes were found to have surface expression of CD44; however, other markers detected (CD105, CD90, CD73, CD106, CD271, and CD133) on mouse CBSCs (mCBSCs) were not detected along with the markers not detected on the surface of mCBSCs (CD45, CD11b, CD31, CD34, CD117, and CD325). Erythrocytes (CD235a) and immune cell markers (CD2, CD3, CD14, CD16, CD19, and CD56) were also not detected. The hCBSCs were found without histocompatibility antigen Ia (MHC-Ia: HLA-A, HLA-B, and HLA-C) and MHC-II (HLA-DR); instead, they expressed soluble forms of MHC-Ib (HLA-G5, HLA-G6, and HLA-G7), potent inhibitor of natural killer cells and other immune cells. These features are commonly found in immune privileged cells. Further, the hCBSCs produced the immunomodulatory and anti-inflammatory factors (IL-4, IL-1RA, TGF-b and IL-10). Additionally, the hCBSCs secreted angiogenic factors that organize endothelial cells into tube like structures. From these results, the hCBSCs we isolated have totally different surface marker characteristics compared to any other known cells including mCBSCs. In addition to their angiogenic effects, the hCBSCs have immunomodulatory properties that could make them suitable for cell therapy targeting inflammatory diseases such post myocardial infarction remodeling.