Abstract
BackgroundMesenchymal stem cells (MSCs) are found in synovial fluid (SF) and can easily be harvested during arthrocentesis or arthroscopy. However, SF-MSC characterization and chondrogenicity in collagen sponges have been poorly documented as well as their hypothetical in vivo chondroprotective properties with intra-articular injections during experimental osteoarthritis (OA).MethodsSF-MSCs were isolated from human SF aspirates in patients suffering from advanced OA undergoing total knee joint replacements. SF-MSCs at passage 2 (P2) were characterized by flow cytometry for epitope profiling. SF-MSCs at P2 were subsequently cultured in vitro to assess their multilineage potentials. To assess their chondrogenicity, SF-MSCs at P4 were seeded in collagen sponges for 4 weeks under various oxygen tensions and growth factors combinations to estimate their gene profile and matrix production. Also, SF-MSCs were injected into the joints in a nude rat anterior cruciate ligament transection (ACLT) to macroscopically and histologically assess their possible chondroprotective properties,.ResultsWe characterized the stemness (CD73+, CD90+, CD105+, CD34−, CD45−) and demonstrated the multilineage potency of SF-MSCs in vitro. Furthermore, the chondrogenic induction (TGF-ß1 ± BMP-2) of these SF-MSCs in collagen sponges demonstrated a good capacity of chondrogenic gene induction and extracellular matrix synthesis. Surprisingly, hypoxia did not enhance matrix synthesis, although it boosted chondrogenic gene expression (ACAN, SOX9, COL2A1). Besides, intra-articular injections of xenogenic SF-MSCs did exert neither chondroprotection nor inflammation in ACLT-induced OA in the rat knee.ConclusionsAdvanced OA SF-MSCs seem better candidates for cell-based constructs conceived for cartilage defects rather than intra-articular injections for diffuse OA.
Highlights
Mesenchymal stem cells (MSCs) are found in synovial fluid (SF) and can be harvested during arthrocentesis or arthroscopy
The objective of this study is to explore the potentialities of an original cell source of MSCs derived from synovial fluid (SF-MSCs) from OA patients undergoing total knee joint replacement (i) to produce cartilage tissue-engineered substitutes to treat focal lesions of cartilage and (ii) the potentialities of intra-articular (i.a.) injections of SF-MSCs to treat experimental knee OA diffuse lesions in the rat
Characterization of human SF-MSCs The characterization of surface epitopes on isolated SF cells was performed at the end of the second passage (P2) demonstrating, as expected [24], that the cells were negative for hematopoietic markers like CD34, CD45, and Human leukocyte antigen - antigen D related (HLA-DR)
Summary
Mesenchymal stem cells (MSCs) are found in synovial fluid (SF) and can be harvested during arthrocentesis or arthroscopy. Articular cartilage has a very limited self-healing potential. Articular cartilage defects are a common problem in orthopedic surgery and can lead to osteoarthritis (OA). Many cells-based treatment strategies for cartilage lesions were developed, and autologous chondrocyte implantation (ACI) is a standard treatment for focal chondral lesions repair [1]. ACI has disadvantages and leads to the formation of fibrotic and hypertrophic cartilage and possible donor site morbidity by risk of OA development [2]. Mesenchymal stem cells (MSCs) are studied as an interesting alternative source of cells for cartilage engineering due to their self-renewal capacity, their accessibility, and their multilineage differentiation capacity. MSCs can be isolated from different adult tissues such as bone marrow, adipose tissue, and synovium or from fetal tissues such as Wharton’s jelly [3]
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