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      In vivo production of mesenchymal stromal cells after injection of autologous platelet-rich plasma activated by recombinant human soluble tissue factor in the bone marrow of healthy volunteers.

      Tissue Engineering. Part A
      Adult, Bone Marrow, drug effects, Cell Differentiation, genetics, Cell Proliferation, Cell Separation, Colony-Forming Units Assay, Cytokines, metabolism, Endothelial Cells, cytology, Female, Fibroblasts, Flow Cytometry, Gene Expression Regulation, Healthy Volunteers, Humans, Injections, Male, Mesenchymal Stromal Cells, Middle Aged, Osteoblasts, Osteogenesis, Platelet-Rich Plasma, Recombinant Proteins, pharmacology, Thromboplastin, Transplantation, Autologous, Young Adult

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          Abstract

          Autologous mesenchymal stromal cell (MSC)-based therapies offer one of the most promising and safe methods for regeneration or reconstruction of tissues and organs. Routine procedures to obtain adequate amount of autologous stem cells need their expansion through culture, with risks of contamination and cell differentiation, leading to the loss of cell ability for therapies. We suggest the use of human bone marrow (BM) as a physiological bioreactor to produce autologous MSC by injection of autologous platelet-rich plasma activated by recombinant human soluble tissue factor (rhsTF) in iliac crest. A trial on 13 healthy volunteers showed the feasibility and harmlessness of the procedure. The phenotype and cellularity of BM cells were not modified, on day 3 after injection. Endothelial progenitor cells (EPC) were mobilized to the bloodstream, without stimulation of hematopoietic stem cells (HSC). MSC level in BM increased with a specific commitment to preosteoblastic cell population both in vivo and in vitro. This self-stimulation system of BM seems thus to be a promising feasible process 3 days before clinical cell therapy applications.

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