Identifying a molecular and cellular phenotype of mesenchymal stem cells mobilized from substance P in the peripheral blood

Abstract

Here we compared MSCs isolated from bone marrow (BMSC) and peripheral blood at 2 days after intravenous substance P (SP) injection (MSCSP) to define specific roles of circulating MSCs in tissue repair process. The mass analysis of changed genes over and under log2 fold showed 97% of genes were identical in these two groups. We found MSCSP increased the molecular signatures related to homing and engraftment (tetraspanin 8, tetraspanin 12), extracellular matrix (ECM) (collagen type IV α1, nidogen 2, laminin-α5, basement membrane components; collagen type XII α1, collagen XV α1, ECM components linking basement membrane to stroma), transmigration (ICAM-1, P-selectin, endothelin), motility (Rho GTPase activating protein 8, myosin heavy chain 10 and 11, troponin C type 1 and 2), transdifferentiation potential (keratin 19, CMTM 8), immunity (IL-1α, IL-33, IL-1R type 1), and angiogenesis (endothelin1, VEGF-C, IL-33, laminin-α5) according to functional classification of the 3 % of changed genes. Functional differences were also shown in MSCSP in regulation of viability of immune cells, Jurkat T cells and U937 monocytes. In addition, a-smooth muscle actin (α-SMA) significantly increased in MSCSP compared with BMSC, demonstrating committed differentiation to myofibroblast participated in tissue repair. However, intrinsic differentiation potential to mesenchymal tissues, adipogenesis and osteogenesis, was not altered in MSCSP. From the molecular and cellular phenotyping of MSCSP, circulating MSCSP seems to be a distinct population mobilized from heterogenous BMSC with well adapted for the participation in tissue repair process by enhancing homing, engraftment, migration, and angiogenesis with multipotent differentiation potential to either myofibroblasts or epithelial-like cells.