Progenitor Cells Activated by Platelet Lysate in Human Articular Cartilage as a Tool for Future Cartilage Engineering and Reparative Strategies

Abstract

Regenerative strategies for human articular cartilage are still challenging despite the presence of resident progenitor cell population. Today, many efforts in the field of regenerative medicine focus on the use of platelet derivatives due to their ability to reactivate endogenous mechanisms supporting tissue repair. While their use in orthopedics continues, mechanisms of action and efficacy need further characterization. We describe that the platelet lysate (PL) is able to activate chondro-progenitor cells in a terminally differentiated cartilage tissue. Primary cultures of human articular chondrocytes (ACs) and cartilage explants were set up from donor hip joint biopsies and were treated in vitro with PL. PL recruited a chondro-progenitors (CPCs)-enriched population from ex vivo cartilage culture, that showed high proliferation rate, clonogenicity and nestin expression. CPCs were positive for in vitro tri-lineage differentiation and formed hyaline cartilage-like tissue in vivo without hypertrophic fate. Moreover, the secretory profile of CPCs was analyzed, together with their migratory capabilities. Some CPC-features were also induced in PL-treated ACs compared to fetal bovine serum (FBS)-control ACs. PL treatment of human articular cartilage activates a stem cell niche responsive to injury. These facts can improve the PL therapeutic efficacy in cartilage applications.

Characterization and Chondroprotective Effects of Extracellular Vesicles From Plasma- and Serum-Based Autologous Blood-Derived Products for Osteoarthritis Therapy

“…Although hypACT EVs and blood product promote inflammation indicated by COX2 expression and IL-6 secretion, respectively, this might be beneficial. As low-grade inflammation is characteristic to OA ( Robinson et al, 2016 ) and might trap cartilage regeneration in a self-perpetuating loop, a short-term inflammatory boost might break the vicious circle to allow progression to later stages of wound healing, dampening inflammation and promoting tissue homeostasis, similar to the effects of the platelet secretome including EVs in wounds after blood coagulation and platelet lysate ( Golebiewska and Poole, 2015 ; Nguyen et al, 2018 ; Carluccio et al, 2020 ).…”

Gene Expression Signatures of Synovial Fluid Multipotent Stromal Cells in Advanced Knee Osteoarthritis and Following Knee Joint Distraction

“…Our results showed clear clustering of chondrocytes away from both types of MSCs indicating toward less-differentiated nature of both types of MSCs. Recent studies have indicated the existence, within the OA cartilage, of highly proliferative and migrating CPCs (Koelling et al, 2009;Fellows et al, 2017;Carluccio et al, 2020), which could in theory, be shed into the SF and contribute to increased levels of matrix-turnover molecules in SF MSCs. Chondrocyte cultures, which were derived from the full-depth OA cartilage in the present study, could also contain the progeny of these migrating CPCs.…”

Platelet Lysate Induces in Human Osteoblasts Resumption of Cell Proliferation and Activation of Pathways Relevant for Revascularization and Regeneration of Damaged Bone

“…We reported that the platelet factors promoted the activation of the cell proliferation machinery and the cell-cycle re-entry of several types of cells, including chondrocytes and chondroprogenitors [ 18 , 19 , 20 ], human umbilical vein endothelial cells [ 21 , 22 ], bone marrow and umbilical cord mesenchymal stromal cells (MSCs) [ 21 , 23 ], adipose tissue cells [ 21 , 23 , 24 ], and amniotic fluid cells [ 25 ].…”