Optimizing Stem Cell Use for Articular Cartilage Regeneration Using PAM-T and PRP

Mariam Hussain

Introduction. Osteoarthritis (OA) is a degenerative joint disease that involves the destruction of articular cartilage and eventually leads to disability. Stems cells have been used as treatment, but there is controversy regarding the efficiency. In this study, we will be focusing on emerging methods of optimizing stem cell use related to articular cartilage regeneration and specifically use of activated platelet rich plasma (PRP) and microspheres releasing TGFβ3 (PAM-T).1-4 Methods. To test PRP’s effect on articular cartilage regeneration, adipose derived stem cells (ADSCs) were isolated and expanded from human adipose tissue. PRP was collected and activated from human peripheral blood. The effects of PRP were evaluated in vitro and in ADSC transplantation in vivo. In vitro, the effects of PRP on ADSC proliferation, differentiation into chondrogenic cells, and inhibition of angiogenic factors were investigated at three concentrations of PRP (10%, 15% and 20%). In vivo, ADSCs pretreated with or without PRP were transplanted into murine models of injured articular cartilage.4 Studies testing PAM-T first evaluated the chondrogenic differentiation of human mesenchymal stem cells (MSCs) seeded onto PAM-T in vitro and confirmed the up-regulation of chondrogenic markers while the secretome of the cells was not changed by the 3D environment. Human MSC was then seeded onto PAM-T in the knee joints of mice with collagenase-induced OA.2 Results. Studies found that PRP promoted ADSC proliferation and differentiation into chondrogenic cells that strongly expressed collagen II, Sox9 and aggrecan. Moreover, PRP inhibited expression of the angiogenic factor vascular endothelial growth factor. As a result, PRP-pretreated ADSCs improved healing of injured articular cartilage in murine models compared with that of untreated ADSCs.4 Studies focusing on PAM-T found that after 6 weeks, histological analysis revealed that formation of a cartilage-like tissue occurred at the vicinity of PAM-T that was not observed when MSCs were seeded onto PAM. Endogenous articular cartilage was also less degraded. The extent of cartilage protection was further analyzed by confocal laser microscopy. When MSCs seeded onto PAM-T were injected early after OA induction, protection of cartilage against degradation was evidenced and this effect was associated to a higher survival of MSCs in presence of TGFβ3.2 Conclusions. Pretreatment of stem cells with PRP and PAM-T are simple methods to efficiently use stem cells in articular cartilage regeneration and should be investigated further.2,4

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  4. Van Pham, P., Bui, K. H. T., Ngo, D. Q., Vu, N. B., Truong, N. H., Phan, N. L. C., … & Phan, N. K. (2013). Activated platelet-rich plasma improves adipose-derived stem cell transplantation efficiency in injured articular cartilage. Stem cell research & therapy, 4(4), 91.