Fibroblastic response to treatment with different preparations rich in growth factors.
OBJECTIVE
Preparations rich in growth factors (PRGF) release them plus bioactive proteins at localized sites, with the aim of triggering healing and regenerative processes. The prevailing paradigm suggests that their influence on proliferation, angiogenesis and the extracellular matrix synthesis is minimal. However, variations in their composition and impact on different cell phenotypes have not been examined.


METHODS
Sixteen fibroblast cultures obtained from three different anatomical sites (skin, synovium and tendon) of 16 donors were exposed to the molecular pool released from PRGF scaffolds, with increasing amounts of platelets. We evaluated cell proliferation, secretion of angiogenic growth factors (VEGF and HGF), synthesis of type I collagen and hyaluronic acid (HA), considering platelet dose and anatomical origin of the cells. Activity of transforming growth factor-beta (TGF-beta) in type I procollagen and HA synthesis was examined by adding exogenous TGF-beta to plasma preparations.


RESULTS
All plasma preparations induced a significant proliferative response compared to non-stimulated cells (P < 0.05). Maximum proliferation rate was obtained with PRGF with 2-fold or 4-fold platelet concentration. Exposure to PRGF stimulated VEGF synthesis exclusively in tendon cells (P < 0.05), which also exhibited a different pattern of HGF production (P < 0.05). PRGF enhanced HA synthesis (P < 0.05), but did not alter collagen I production. Platelet-secreted TGF-beta may be involved in HA, but not in type I procollagen synthesis.


CONCLUSIONS
Optimizing composition and use of platelet-rich products is crucial to enhancing the therapeutic potential of this technology. Our data show that the biological effects of PRGF may depend on concentration of platelets and on the anatomical source of the cells.
Anitua
E
E
Biotechnology Institute, BTI IMASD, Vitoria-Gasteiz, Spain.
Sánchez
M
M
Zalduendo
M M
MM
de la Fuente
M
M
Prado
R
R
Orive
G
G
Andía
I
I
D001688:Biological Products / Q000494:pharmacology; D001777:Blood Coagulation; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D017077:Culture Media, Conditioned; D005337:Fibrin / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000494:pharmacology*; D008297:Male; D053657:Platelet-Rich Plasma / Q000737:chemistry / Q000378:metabolism; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D012867:Skin / Q000166:cytology; D013583:Synovial Membrane / Q000166:cytology; D013710:Tendons / Q000166:cytology; D018800:Thy-1 Antigens / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D001688:Biological Products; D024042:Collagen Type I; D017077:Culture Media, Conditioned; C066855:HGF protein, human; D036341:Intercellular Signaling Peptides and Proteins; D018800:Thy-1 Antigens; D053773:Transforming Growth Factor beta1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor; D005337:Fibrin; D006820:Hyaluronic Acid; D011393:Procollagen-Proline Dioxygenase