A Novel Arthroscopic Technique for Intraoperative Mobilization of Synovial Mesenchymal Stem Cells

Abstract

Background: Mesenchymal stem cells (MSCs) have emerged as a promising candidate for tissue regeneration and restoration of intra-articular structures such as cartilage, ligaments, and menisci. However, the routine use of MSCs is limited in part by their low numbers and the need for methods and procedures outside of the joint or surgical field. Purpose: To demonstrate feasibility of a technique in which minimally manipulated synovial MSCs can be mobilized during knee arthroscopy, thereby showing proof of concept for the future evaluation and clinical use of native joint resident MSCs in single-stage joint repair strategies. Study Design: Descriptive laboratory study. Methods: Patients (n = 15) undergoing knee arthroscopy who were free from synovitis or active inflammation were selected. Three samples of irrigation fluid were collected from each patient at inception of the procedure, after an initial inspection of the joint, and after agitation of the synovium. MSC numbers were evaluated by colony forming unit–fibroblastic assay. The phenotype of synovial fluid resident and synovial-mobilized MSCs was determined by flow cytometry, and their functionality was determined by trilineage differentiation. Adhesion of culture-expanded mobilized MSCs to fibrin scaffolds was also evaluated to ascertain whether mobilized MSCs might concentrate at sites of bleeding. Results: Normal irrigation during arthroscopy depleted resident synovial fluid MSCs (4-fold decrease, n = 15). Numbers of MSCs mobilized through use of a purpose-made device were significantly higher (105-fold) than those mobilized through use of a cytology brush (median of 5763 and 54 colonies, respectively; P = .001; n = 15). The mobilized cellular fraction contained viable MSCs with proliferative potential and trilineage differentiation capacity for bone, cartilage, and fat lineages, and cultured daughter cells exhibited the standard MSC phenotype. Following culture, mobilized synovial MSCs also adhered to various fibrin scaffolds in vitro. The technique was simple and convenient to use and was not associated with any complications. Conclusion: Numbers of functional MSCs can be greatly increased during arthroscopy through use of this technique to mobilize cells from the synovium. Clinical Relevance: This study highlights a novel, single-stage technique to increase joint-specific, synovial-derived MSCs and thereby increase the repair potential of the joint. This technique can be undertaken during many arthroscopic procedures, and it supports the principle of integrating mobilized MSCs into microfracture sites and sites of bleeding or targeted repair through use of fibrin-based and other scaffolds.