Abstract
BackgroundOsteoarthritis (OA) is the most common joint degenerative disorder, with little effective therapy to date. Nanofat is a cocktail of cells obtained from fat tissue, which possesses regenerative capacity and has a potential in treating OA. This study aimed to determine the anti-OA efficacy of Nanofat from basic and clinical aspects and explore its action mode.MethodsFlow cytometry was performed to characterize Nanofat. A monoiodoacetate-induced OA rat model was employed for in vivo study. Cell viability and wound healing assays were conducted for in vitro study. Real-time PCR and Western blot assays were applied to explore the molecular action mode of Nanofat. Moreover, a retrospective analysis was conducted to determine the clinical efficacy and safety of Nanofat on knee OA patients.ResultsThe in vivo results showed that Nanofat significantly attenuated pain symptoms and protected cartilage ECM (Col2) from damage, and its effects were not significantly differed with adipose tissue-derived stem cells (both P > 0.05). The in vitro results showed that Nanofat promoted the cell viability and migration of chondrocytes and significantly restored the IL-1β-induced abnormal gene expressions of Col2, Aggrecan, Sox9, Adamts5, Mmp3, Mmp9 Mmp13, IL-6 and Col10 and protein expressions of Col2, MMP9, MMP13, and Sox9 of chondrocytes. The regulatory actions of Nanofat on these anabolic, catabolic, and hypertrophic molecules of chondrocytes were similar between two treatment routes: co-culture and conditioned medium, suggesting a paracrine-based mode of action of Nanofat. Moreover, the clinical data showed that Nanofat relieved pain and repaired damaged cartilage of OA patients, with no adverse events.ConclusionIn sum, this study demonstrated the anti-OA efficacy as well as a paracrine-based action mode of Nanofat, providing novel knowledge of Nanofat and suggesting it as a promising and practical cell therapy for clinical treatment of OA.
Highlights
Osteoarthritis (OA) is the most common joint degenerative disorder, affecting hundreds of thousands of patients around the world, especially the middle-aged and old people [1]
Nanofat expressed the classical adipose-derived mesenchymal stem cells (MSCs) (ADSCs) markers including CD29, CD44 and CD90, which was in line with another study [23, 30, 31], while the high expression of CD34, CD29 and CD90 could indicate the existence of endothelial progenitor cells, pericytes and vascular smooth muscle cells [23]
Therapeutic effects of Nanofat and ADSCs on osteoarthritic rats To study the potential effects of Nanofat and ADSCs on OA, we constructed a rat OA model by articular injection of MIA
Summary
Osteoarthritis (OA) is the most common joint degenerative disorder, affecting hundreds of thousands of patients around the world, especially the middle-aged and old people [1]. Pharmaceutical treatment is a conventional strategy for OA before surgery, applying nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, local analgesics, corticosteroid injection and hyaluronic acid injection [6]. These treatments are usually palliative and merely provide symptomatic relief from pain, failing to prevent cartilage damage and subsequent destruction of other joint tissues [7]. Osteoarthritis (OA) is the most common joint degenerative disorder, with little effective therapy to date. This study aimed to determine the anti-OA efficacy of Nanofat from basic and clinical aspects and explore its action mode
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