Abstract
We investigated the effects of intra-articular injections of alginate-microencapsulated adipose tissue-derived mesenchymal stem cells (ASCs) during osteoarthritis (OA) development in a rabbit model of anterior cruciate ligament transection (ACLT). We induced OA in mature New Zealand white rabbits by bilateral ACLT. Stifle joints were categorised into four groups according to intra-articular injection materials. Alginate microbeads and microencapsulated ASCs were prepared using the vibrational nozzle technology. Two weeks after ACLT, the rabbits received three consecutive weekly intra-articular injections of 0.9% NaCl, alginate microbeads, ASCs, or microencapsulated ASCs, into each joint. Nine weeks after ACLT, we euthanised the rabbits and collected bilateral femoral condyles for macroscopic, histological, and immunohistochemical analyses. Macroscopic evaluation using the modified OA Research Society International (OARSI) score and total cartilage damage score showed that cartilage degradation on the femoral condyle was relatively low in the microencapsulated-ASC group. Histological analysis of the lateral femoral condyles indicated that microencapsulated ASCs had significant chondroprotective effects. Immunohistochemically, the expression of MMP-13 after the articular cartilage damage was relatively low in the microencapsulated-ASC-treated stifle joints. During the development of experimental OA, as compared to ASCs alone, intra-articular injection of microencapsulated ASCs significantly decreased the progression and extent of OA.
Highlights
Degenerative joint disease or osteoarthritis (OA) of the knee is the most common form of arthritis and reduces quality of life by causing pain, stiffness, and physical disability [1]
We investigated the effects of periodic intra-articular injection of alginate-microencapsulated adipose tissue-derived mesenchymal stem cells (ASCs) on OA in a rabbit model of anterior cruciate ligament transection (ACLT)
To determine the total cartilage damage score (TCDS), femoral condyles were graded based on ink retention; quantification of a defect region in femoral condyles was conducted in ImageJ (NIH, Bethesda, MD, USA): image analysis software
Summary
Degenerative joint disease or osteoarthritis (OA) of the knee is the most common form of arthritis and reduces quality of life by causing pain, stiffness, and physical disability [1]. Many treatments with MSCs have been developed, adipose tissue-derived mesenchymal stem cells (ASCs) have several advantages. Intra-articular injection of ASCs improves the functioning and reduces pain and cartilage defects of the knee joint [11]. Systemic or local stem cell-based therapies represent a growing field of treatment of OA, resulting in repair of articular cartilage [15]. Most therapeutic effects of MSCs are thought to act in a paracrine manner by promoting angiogenesis, tissue regeneration, and production of soluble anti-inflammatory factors [16, 22, 23]. Alginatemicroencapsulated cells provide a mechanical barrier that acts as an artificial extracellular matrix, increasing cell viability and allowing for a release of stem cell-produced growth factors and anti-inflammatory factors into surrounding injured tissue [24]. We hypothesised that the microencapsulated ASCs would reduce OA progression more effectively than ASCs alone would
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