Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 22, Issue 3, Pages 1840-1854Publisher
WILEY
DOI: 10.1111/jcmm.13468
Keywords
circulating multipotent cells; haemoderivatives; in vivo guided regeneration; autologous cell therapies
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Funding
- Foundation for Biology and Regenerative Medicine, Tissue Engineering and Signaling (TES) ONLUS (Padova, Italy)
- Associazione Volontari Italiani del Sangue/A.V.I.S. Regionale Veneto (Treviso, Italy)
- Associazione Bellunese Volontari del Sangue/A.B.V.S (Belluno, Italy)
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The wound healing is a complex process wherein inflammation, proliferation and regeneration evolve according to a spatio-temporal pattern from the activation of coagulation cascade to the formation of a plug clot including fibrin matrix, blood-borne cells and cytokines/growth factors. Creating environments conducive to tissue repair, the haemoderivatives are commonly proposed for the treatment of hard-to-heal wounds. Here, we explored in vitro the intrinsic regenerative potentialities of a leucocyte- and platelet-rich fibrin product, known as CPL-MB, defining the stemness grade of cells sprouting from the haemoderivative. Using highly concentrated serum-based medium to simulate wound conditions, we isolated fibroblast-like cells (CPL-CMCs) adhering to plastic and showing stable in vitro propagation, heterogeneous stem cell expression pattern, endothelial adhesive properties and immunomodulatory profile. Due to their blood derivation and expression of CXCR4, CPL-CMCs have been suggested to be immature cells circulating in peripheral blood at quiescent state until activation by both coagulation event and inflammatory stimuli such as stromal-derived factor 1/SDF1. Expressing integrins (CD49f, CD103), vascular adhesion molecules (CD106, CD166), endoglin (CD105) and remodelling matrix enzymes (MMP2, MMP9, MMP13), they showed a transendothelial migratory potential besides multipotency. Taken together, our data suggested that a standardized, reliable and economically feasible blood product such as CPL-MB functions as an artificial stem cell niche that, under permissive conditions, originate ex vivo immature cells that could be useful for autologous stem cell-based therapies.
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