Cell-free fat extract attenuates osteoarthritis via chondrocytes regeneration and macrophages immunomodulation

Abstract

Background The prevalence of osteoarthritis (OA) is increasing, yet clinically effective and economical treatments are unavailable. We have previously proposed a cell-free fat extract (CEFFE) containing multiple cytokines, which possessed antiapoptotic, anti-oxidative, and proliferation promotion functions, as a “cell-free” strategy. In this study, we aimed to evaluate the therapeutic effect of CEFFE in vivo and in vitro. Methods In vivo study, sodium iodoacetate-induced OA rats were treated with CEFFE by intra-articular injections for 8 weeks. Behavioral experiments were performed every two weeks. Histological analyses, anti-type II collagen, and toluidine staining provided structural evaluation. Macrophage infiltration was assessed by anti-CD68 and anti-CD206 staining. In vitro study, the effect of CEFFE on macrophage polarization and secretory factors was evaluated by flow cytometry, immunofluorescence, and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The effect of CEFFE on cartilage regeneration was accessed by cell counting kit-8 assay and qRT-PCR. The generation of reactive oxygen species (ROS) and levels of ROS-related enzymes were investigated by qRT-PCR and western blotting. Results In rat models with sodium iodoacetate (MIA)-induced OA, CEFFE increased claw retraction pressure while decreasing bipedal pressure in a dose-dependent manner. Moreover, CEFFE promoted cartilage structure restoration and increased the proportion of CD206+ macrophages in the synovium. In vitro, CEFFE decreased the proportion of CD86+ cells and reduced the expression of pro-inflammatory factors in LPS + IFN-γ induced Raw 264.7. In addition, CEFFE decreased the expression of interleukin-6 and ADAMTs-5 and promoted the expression of SOX-9 in mouse primary chondrocytes. Besides, CEFFE reduced the intracellular levels of reactive oxygen species in both in vitro models through regulating ROS-related enzymes. Conclusions CEFFE inhibits the progression of OA by promoting cartilage regeneration and limiting low-grade joint inflammation. Graphical abstract

Fat Extract Modulates Calcium Signaling and Protects against Hyperactive Osteoclastogenesis in Bone Remodeling with Antioxidant Capacity

“…[ 29 ] Jia et al found that CEFFE inhibited osteoarthritis progression via promoting cartilage regeneration and limiting joint inflammation. [ 30 ] These findings highlight the multifaceted impact of CEFFE on bone homeostasis. In addition, CEFFE could also enhance soft tissue regeneration and even rejuvenate aging cells.…”

Pro-vasculogenic Fibers by PDA-Mediated Surface Functionalization Using Cell-Free Fat Extract (CEFFE)

“…This benefited for not only the growth and functional expression of ECs but also modulating macrophages into the anti-inflammatory phenotype, as also confirmed in our study (Figure S5). It is likely that the presented multiple growth factors in FE may function synergistically to stimulate vascularization. − While it is the previously demonstrated pro-angiogenic effect of FE that initiated our current effort for engineering pro-vasculogenic fibers, increasing evidence suggests that our FE, derived from healthy young women of different ages (22–35 years old) , in different locations of the body (e.g., abdomen, thighs, and upper arms) with relatively stable concentrations of the major growth factors, has omnipotent biological functions in the treatment of different diseases, such as ischemic stroke, osteoporosis, osteoarthritis, spinal cord injuries, chronic wound healing, reproductive related disorders, , and so on. With the multifaceted actions identified in FE, in tandem with its cell recruitment capability observed in our current study (Figures E,F and S1) and elsewhere, the FE-PDA@PCL/GT fiber system will be well suitable for engineering 3D fibrous scaffolds , for in situ regeneration of different tissues.…”

Regeneration of articular cartilage defects: Therapeutic strategies and perspectives

“…For example, CEFFE attenuates osteoarthritis via chondrocyte regeneration and macrophage immunomodulation. 192 In addition, PRP may promote AC lubrication and regeneration, and retards the progression of OA by stimulating cell migration, proliferation, differentiation of progenitor/MSCs, joint homeostasis, and joint lubrication. 193 , 194 The function of BMSCs extracted exosomes was verified in vitro and in OA model in vivo.…”