Leucocyte and Platelet-rich Fibrin: a carrier of autologous multipotent cells for regenerative medicine

J Cell Mol Med. 2018 Mar;22(3):1840-1854. doi: 10.1111/jcmm.13468. Epub 2018 Jan 5.

Abstract

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.

Keywords: autologous cell therapies; circulating multipotent cells; haemoderivatives; in vivo guided regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis / drug effects
  • Adipogenesis / genetics
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Gene Expression Profiling / methods
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Leukocytes / metabolism*
  • Multipotent Stem Cells / cytology
  • Multipotent Stem Cells / drug effects
  • Multipotent Stem Cells / metabolism*
  • Neurogenesis / drug effects
  • Neurogenesis / genetics
  • Platelet-Rich Fibrin / metabolism*
  • Proteomics / methods
  • Regenerative Medicine / methods*
  • Wound Healing / drug effects

Substances

  • Intercellular Signaling Peptides and Proteins

Associated data

  • GENBANK/NM_003236.3
  • GENBANK/NM_000660.6
  • GENBANK/NM_002309.4
  • GENBANK/NM_000575.4
  • GENBANK/NM_000576.2
  • GENBANK/NM_000589.3
  • GENBANK/NM_000600.4
  • GENBANK/NM_000572.2
  • GENBANK/NM_000882.3
  • GENBANK/FJ795028.1
  • GENBANK/AH003016.2
  • GENBANK/NM_001066.2
  • GENBANK/NM_174900.3
  • GENBANK/NM_003106.3
  • GENBANK/NM_213662.1
  • GENBANK/NM_017617.3
  • GENBANK/NM_002701.4
  • GENBANK/NM_004235.4
  • GENBANK/NM_024865.2
  • GENBANK/NM_006086.3
  • GENBANK/NM_000552.4
  • GENBANK/NM_000442.4
  • GENBANK/NM_000194.2
  • GENBANK/AE2000