Autologous Fat Transfer Decreases the Expression of IL-1B in an in vitro Model of Basal Joint Osteoarthritis
Christopher G Larsen, MD, Brandon Alba, BA, Travis A Doering, MD, Yen Chen, MD, Daniel Grande, PhD, Armen K Kasabian, MD, Kate Nellans, MD, MPH and Lewis B Lane, MD, Northwell Health, New Hyde Park, NY
Basal joint osteoarthritis (OA) is a debilitating condition, affecting up to 36% of postmenopausal women. Conservative management includes splinting, hand therapy, and NSAIDs. For more advanced disease, steroid injections are the mainstay of treatment. However, symptomatic relief tends to be short-lived, and many patients seek surgical intervention. Recent clinical evidence suggests that autologous fat transfer (AFT) may be a promising means to treat this condition. Autologous fat obtained from liposuction is prepared and injected into the basal joint, with improvements in pain and function scores. The purpose of this study is to better understand the underlying mechanism of this therapy using in vitro cell culture.
Articular chondrocytes were isolated from human subjects and expanded in culture. Liposuction samples from human subjects were collected and processed to isolate adipose-derived stromal vascular fraction (SVF) cells. Chondrocytes were plated at 50,000 cells per well. A negative control group was treated with standard growth media and a positive control group, or OA group, was treated with inflammatory cytokines IL-IB and oncostatin-M (OSM). To mimic the injection of autologous fat, experimental groups received IL-1B + OSM plus either a low-dose or high dose of SVF cells. RT- PCR was performed at days 1-3 after treatment to measure gene expression of various inflammatory and anti-inflammatory genes, including IL-1B, IL-1 receptor antagonist (IL-1 RA), and matrix metalloproteinases (MMPs).
Compared to the OA group, the SVF-treated groups demonstrated a decrease in IL-1B expression at all timepoints. IL-1 RA expression also decreased in both SVT treated groups and was comparable to negative control levels. MMP13 expression was decreased in both the SVF treated groups relative to the OA group on day 3, but otherwise no trends were seen for expression of MMP 3, 9, or 13.
The results of this study suggest that AFT may function to decrease inflammation in basal joint osteoarthritis, as seen by changes in cytokine expression in vitro. Compared to the positive control group, the addition of adipose-derived SVF cells to chondrocytes grown in an inflammatory milieu significantly reduced the expression of IL-1B, an important inflammatory marker in osteoarthritis. Expression of IL-1 RA, an anti-inflammatory mediator was decreased in treatment groups, possibly indicating that with reduced inflammation chondrocytes need not upregulate this gene. No significant trends were noted for MMP expression. Further studies are underway to examine gene expression at a greater number of timepoints to better understand these anti-inflammatory properties.
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