title: Platelet-rich plasma releasate differently stimulates cellular commitment toward the chondrogenic lineage according to concentration.
abstract: Platelet-rich plasma has been used to treat articular cartilage defects, with the expectations of anabolic and anti-inflammatory effects. However, its role on cellular chondrogenic or fibrogenic commitment is still a controversy. Herein, the role of platelet-rich plasma releasate, the product obtained following platelet-rich plasma activation, on cellular commitment toward the chondrogenic lineage was evaluated in vitro. Human nasoseptal chondrogenic cells and human bone marrow mesenchymal stromal cells were used as cell types already committed to the chondrogenic lineage and undifferentiated cells, respectively, as different concentrations of platelet-rich plasma releasate were tested in comparison to commonly used fetal bovine serum. Low concentration of platelet-rich plasma releasate (2.5%) presented similar effects on cellular growth compared to 10% fetal bovine serum, for both cell types. In a three-dimensional culture system, platelet-rich plasma releasate alone did not induce full nasoseptal chondrogenic cells cartilage-like pellet formation. Nonetheless, platelet-rich plasma releasate played a significant role on cell commitment as high-passage nasoseptal chondrogenic cells only originated cartilage-like pellets when expanded in the presence of platelet-rich plasma releasate rather than fetal bovine serum. Histological analyses and measurements of pellet area demonstrated that even low concentrations of platelet-rich plasma releasate were enough to prevent nasoseptal chondrogenic cells from losing their chondrogenic potential due to in vitro expansion thereby promoting their recommitment. Low concentration of platelet-rich plasma releasate supplemented in chondrogenic medium also increased the chondrogenic potential of mesenchymal stromal cells seeded on collagen-hyaluronic acid scaffolds, as observed by an increase in chondrogenic-related gene expression, sulfated glycosaminoglycan production, and compressive modulus following in vitro culture. On the contrary, higher concentration of platelet-rich plasma releasate (10%) hampered some of these features. In conclusion, platelet-rich plasma releasate was able to prevent cellular chondrogenic capacity loss, inducing regain of their phenotype, and modulate cell commitment. Our data support the hypothesis of platelet-rich plasma chondrogenic potential, allowing fetal bovine serum substitution for platelet-rich plasma releasate at specific concentrations in culture medium when chondrogenic commitment is desired on specific cell types and moments of culture.
authors.affiliation: Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brasil ; Excellion Serviços Biomédicos, Amil/UnitedHealth Group, Petrópolis, Brasil.
authors.forename: Ronaldo Jfc
authors.initials: RJ
authors.lastname: do Amaral
authors.affiliation: Tissue Engineering Research Group, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland ; Trinity Centre for Bioengineering, Trinity College Dublin (TCD), Dublin, Ireland ; Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI & TCD, Dublin, Ireland.
authors.forename: Amos
authors.initials: A
authors.lastname: Matsiko
authors.affiliation: Laboratório de Biologia e Tecnologia Celular, Universidade Veiga de Almeida, Rio de Janeiro, Brasil.
authors.forename: Marcel Rp
authors.initials: MR
authors.lastname: Tomazette
authors.affiliation: Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti, Rio de Janeiro, Brasil.
authors.forename: Wanessa Kr
authors.initials: WK
authors.lastname: Rocha
authors.affiliation: Laboratório de Biologia e Tecnologia Celular, Universidade Veiga de Almeida, Rio de Janeiro, Brasil.
authors.forename: Eric
authors.initials: E
authors.lastname: Cordeiro-Spinetti
authors.affiliation: Tissue Engineering Research Group, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland ; Trinity Centre for Bioengineering, Trinity College Dublin (TCD), Dublin, Ireland ; Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI & TCD, Dublin, Ireland.
authors.forename: Tanya J
authors.initials: TJ
authors.lastname: Levingstone
authors.affiliation: Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brasil.
authors.forename: Marcos
authors.initials: M
authors.lastname: Farina
authors.affiliation: Tissue Engineering Research Group, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland ; Trinity Centre for Bioengineering, Trinity College Dublin (TCD), Dublin, Ireland ; Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI & TCD, Dublin, Ireland.
authors.forename: Fergal J
authors.initials: FJ
authors.lastname: O'Brien
authors.affiliation: Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brasil.
authors.forename: Marcia C
authors.initials: MC
authors.lastname: El-Cheikh
authors.affiliation: Excellion Serviços Biomédicos, Amil/UnitedHealth Group, Petrópolis, Brasil ; Laboratório de Biologia e Tecnologia Celular, Universidade Veiga de Almeida, Rio de Janeiro, Brasil.
authors.forename: Alex
authors.initials: A
authors.lastname: Balduino
keywords: Platelet-rich plasma; cartilage repair; chondrogenesis; mesenchymal stromal cells; nasoseptal chondrogenic cells