Establishment of optimal tissue regenerating procedures using monocyte-derived multipotential cells for tissue regeneration

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We recently discovered a primitive human cell population called monocyte-derived multipotential cells (MOMC), which has a fibroblast-like morphology and a unique phenotype positive for CD14, CD45, CD34, and type I collagen. MOMC contain progenitors with capacity to differentiate into a variety of non-phagocytes, including bone, cartilage, fat, skeletal and cardiac muscle, neuron, and endothelium. This study was aimed to assess efficacy of MOMC transplantation in tissue regeneration and to establish optimal culture conditions that generate MOMC for tissue regeneration therapy.1)Evaluation of efficacy of MOMC transplantation in animal modelsEfficacy of transplantation of syngeneic MOMC was assessed using 2 different rat models, including cerebral infarction and skin flap procedure. Rats were subjected to 1 hour of left middle cerebral artery occlusion and received intra-cranial transplantation of MOMCs at day 7. Neurological function assessed by Corner test was improved in rats transplan … More ted of MOMC, but not in control rats transplanted of macrophages or medium alone. In immunohistochemical analysis, the number of newly formed blood vessels was significantly increased in MOMC-transplanted rats, compared with controls rats. Transplanted MOMC were confirmed to be incorporated in blood vessel wall and differentiate into endothelial cells. A principally concordant finding regarding functional improvement and in vivo differentiation of MOMC to endothelial cells was obtained from rat skin flap model.2)Establishment of optimal culture conditions that generate human MOMCWe previously found that MOMC can be enriched in culture of human peripheral blood mononuclear cells on fibronectin-coated plastic plates in the presence of soluble factor(s) derived from activated platelets. Potential platelet-derived factors with such capacity were screened by culturing circulating monocytes in the presence or absence of candidate molecules with molecular weight < 30,000, which were released upon platelet activation. As a result, SDF-1 was identified as a factor that promotes MOMC generation. Based on this, we have successfully developed an ex vivo procedure that generates a large number of human MOMC by culturing circulating monocytes on recombinant fibronectin with exogenous SDF-1.These findings together indicate that MOMC transplantation is a promising strategy that regenerates the damaged tissue. Less