STROME-DEPENDENT EXPANSION OF HEMOPOIETIC PRECURSORS DURING 7-DAY MODELING OF THE EFFECTS OF MICROGRAVITY

It is well known that long-term space missions influence various myeloid shoots of hemopoiesis in humans and animals. In this investigation, we used several optimized models of co-culturing mesenchymal stromal cells (MSCs) and hemopoietic stem and progenitor cells (HSPCs) to analyze the HSPCs suspension fractions following 7-day modeling of the effects of microgravity. We determined the number of developing HSPCs, presence of colony-forming units (CFU) of various hemopoietic shoots and phenotype spectrum of cells in colonies. We observed an increased number of HSPCs, decreased number of CFUs, and changes in the structure of CFU population after the exposure to modeled microgravity.

Interleukin-3 promotes expansion of hemopoietic-derived CD45+ angiogenic cells and their arterial commitment via STAT5 activation

Interleukin-3 (IL-3) released by infiltrating inflammatory cells in different pathologic settings contributes to organ and tumor angiogenesis. Here we demonstrate that IL-3 expands a subset of CD45+ circulating angiogenic cells clonally derived from the hemopoietic progenitors. Moreover, CD45+ cells exposed to IL-3 acquire arterial specification and contribute to the formation of vessels in vivo. Depletion of signal transducer and activator of transcription 5 (STAT5) provides evidence that IL-3–mediated cell expansion and arterial morphogenesis rely on STAT5 activation. In addition, by means of Tie2-transgenic mice, we demonstrate that STAT5 also regulates IL-3–induced expansion and arterial specification of bonemarrow–derived CD45+ cells. Thus, our data provide the first evidence that, in inflammatory microenvironments containing IL-3, angiogenic cells derived from hemopoietic precursors can act as adult vasculogenic cells. Moreover, the characterization of the signaling pathway regulating these events provides the rationale for therapeutically targeting STAT5 in these pathologic settings.