Effects of Conditioned Medium From Osteoarthritic Cartilage Fragments on Donor-Matched Infrapatellar Fat Pad–Derived Mesenchymal Stromal Cells

Abstract

Background: Mesenchymal stromal cell (MSC)–based therapies have emerged as a promising strategy for osteoarthritis (OA) treatment. In particular, infrapatellar fat pad (IPFP)–derived MSCs have become a good option to treat knee OA. Purpose: To investigate the influence of the local microenvironment of the knee joint, especially OA cartilage, on the bioactivities of injected/implanted IPFP MSCs. Study Design: Controlled laboratory study. Methods: Conditioned medium (CM) derived from OA cartilage fragments was collected and characterized. Donor-matched IPFP MSCs were treated with control medium (Dulbecco’s modified Eagle medium (DMEM)/F-12 or chondrogenic medium), control medium + CM, or CM alone; and a series of behaviors including the viability, migration, chondrogenic and hypertrophic differentiation, and catabolic activity of IPFP MSCs were evaluated among groups. Results: There were 14 cytokines detected in CM. CM treatment improved the viability of IPFP MSCs. CM hindered the migration of IPFP MSCs. In chondrogenic differentiation, the presence of CM increased the expression of chondrogenic markers but also enhanced the state of hypertrophy and catabolism. Conclusion: OA cartilage–secreted factors could induce chondrogenic differentiation but also resulted in negative effects including the weakened migration, increased hypertrophy, and catabolism of IPFP MSCs in vitro. Clinical Relevance: These findings provide an insight on the fate of IPFP MSCs after intra-articular injections.

Tropoelastin improves adhesion and migration of intra-articular injected infrapatellar fat pad MSCs and reduces osteoarthritis progression

“…Firstly, human infrapatellar fat pads were obtained from OA patients, and IPFP-MSCs were isolated according to the methods described in our pervious study [ 40 ] ( Fig. S1A ).…”

Mechanical dissection and culture of mouse cranial neural crest cells

“…These findings suggest that the origin as well as the application of the medium are the same between the two types of cells. In addition, DMEM: F12 is commonly used in stem cell cultures, such as human subcutaneous fat-derived mesenchymal stem cells (Dhanasekaran, Indumathi, Rashmi, Rajkumar, & Sudarsanam, 2012) and infrapatellar fat pad-derived mesenchymal stromal cells (Fu, Song, Guo, Yang, & Chen, 2019). DMEM: F12 combines high concentrations of glucose, amino acids, and vitamins with various components of F-12, which contain zinc, putrescine, hypoxanthine, and thymidine.…”

Source and hub of inflammation: The infrapatellar fat pad and its interactions with articular tissues during knee osteoarthritis

“…42 In contrast, cocultures of IFP-MSCs with OA cartilage fragment derived conditioned medium have been shown to reduce the migration potential of IFP-MSC, mediate a hypertrophic differentiation phenotype and enhance catabolic signaling pathways. 43 These stark differences likely result from different experimental setups, treatment durations and compositions of the chondrogenic culture media used.…”

“…Cocultures of chondrocytes and IFP‐MSCs can promote chondrogenic differentiation of IFP‐MSCs, 41 and suppression of chondrocyte inflammation and MSC hypertrophy when compared to either of the cell populations cultured alone 42 . In contrast, cocultures of IFP‐MSCs with OA cartilage fragment derived conditioned medium have been shown to reduce the migration potential of IFP‐MSC, mediate a hypertrophic differentiation phenotype and enhance catabolic signaling pathways 43 . These stark differences likely result from different experimental setups, treatment durations and compositions of the chondrogenic culture media used.…”