Abstract
The tissue engineering approach in osteoarthritic cell therapy often requires the delivery of a substantially high cell number due to the low engraftment efficiency as a result of low affinity binding of implanted cells to the targeted tissue. A modification towards the cell membrane that provides specific epitope for antibody binding to a target tissue may be a plausible solution to increase engraftment. In this study, we intercalated palmitated protein G (PPG) with mesenchymal stem cells (MSCs) and antibody, and evaluated their effects on the properties of MSCs either in monolayer state or in a 3D culture state (gelatin microsphere, GM). Bone marrow MSCs were intercalated with PPG (PPG-MSCs), followed by coating with type II collagen antibody (PPG-MSC-Ab). The effect of PPG and antibody conjugation on the MSC proliferation and multilineage differentiation capabilities both in monolayer and GM cultures was evaluated. PPG did not affect MSC proliferation and differentiation either in monolayer or 3D culture. The PPG-MSCs were successfully conjugated with the type II collagen antibody. Both PPG-MSCs with and without antibody conjugation did not alter MSC proliferation, stemness, and the collagen, aggrecan, and sGAG expression profiles. Assessment of the osteochondral defect explant revealed that the PPG-MSC-Ab micromass was able to attach within 48 h onto the osteochondral surface. Antibody-conjugated MSCs in GM culture is a potential method for targeted delivery of MSCs in future therapy of cartilage defects and osteoarthritis.
Highlights
Osteoarthritis (OA) is a chronic degenerative disease of the joints characterized by articular cartilage degeneration of the knee, hip, or hand; synovitis; and the loss of extracellular matrix, accompanied by progressive pain and functional impairment [1]
We found that incubating the mesenchymal stem cells (MSCs) with palmitated protein G (PPG) did not affect their proliferation and differentiation regardless of the cell culture environments, demonstrating the inert effect of PPG on cell biology
We demonstrated that coating the cell surface with PPG does not interfere or affect the proliferation and stemness profile and differentiation ability of MSCs
Summary
Osteoarthritis (OA) is a chronic degenerative disease of the joints characterized by articular cartilage degeneration of the knee, hip, or hand; synovitis; and the loss of extracellular matrix, accompanied by progressive pain and functional impairment [1]. OA is one of the leading causes of chronic pain and disability, with 17.1 million people living with disability globally [2]. Due to the risk of failure and morbidity in the conventional treatments, the potential applicability of cell therapy and tissue engineering for treating OA were explored [4]. Cell-based therapies for the treatment of OA are not foreign; numerous studies have reported beneficial effects [5,6]. The therapies feature delivery of cells, in particular, mesenchymal stem cells (MSCs) to the knee by means of direct injection or implantation [7,8]
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