Abstract
Background
Carpometacarpal osteoarthritis is a degenerative disease of the hand that causes pain, stiffness and weakness. Currently, no drugs are available to prevent progression or cure this disease. Ultimately, the last treatment option is the surgical removal of the trapezium bone. In order to this limited treatment options, the utilization of autologous fat injections or adipose-derived stem progenitor cells (ADSPCs) provides a novel treatment option to inhibit the progression of this disease and potentially regenerate the damaged tissue.
Objective
By utilizing next-generation-sequencing (NGS), we aim to uncover novel factors, released by ADSPCs or whole-fat aspirates, that might be involved into the metabolism of osteoarthritic cartilage.
Materials and Methods
Human fat tissue was collected from five patients undergoing abdominal liposuction. Fat- and ADSPCs-conditioned medium was prepared by incubating fat and ADSPCs for 48 h in culture medium with and without TNFα to stimulate the secretion of immunomodulatory factors. The transcriptome of stimulated and non-stimulated fat and ADSPCs was analyzed by NGS. Chondrocytes from osteoarthritic cartilage from seven patients undergoing trapeziectomy were isolated, expanded and pooled. Chondrocytes were treated with six different conditions for 72 h. While standard culture medium with and without TNFα served as control groups. Fat-conditioned medium with and without TNFα, as well as ADSPCs-conditioned medium with and without TNFα served as experimental groups. Before and after cultivation of osteoarthritic chondrocytes with conditioned medium, chondrocytes were analyzed by NGS to evaluate the effect of fat- and ADSPCs-conditioned medium onto transcriptional changes in osteoarthritic chondrocytes.
Results
To determine which factors might be involved in the anti-inflammatory effect of fat- and ADSPCs- conditioned medium, stimulated and non-stimulated fat and ADSPCs were analyzed by NGS. The most promising genes are cytokines, tissue inhibitors of matrix metalloproteinases and growth factors. In order to see the effect of conditioned medium from fat and ADSPCs on chondrocytes before and after cultivation with conditioned medium, NGS was performed. The gene expression of matrix metalloproteinases, cytokines, suppressors of cytokine signaling and cartilage specific proteins is of special interest.
Conclusion
We aimed to investigate in our study if the clinically approved fat injection into osteoarthritic joints has the same therapeutical effect as the not yet clinically approved injection of isolated ADSPCS. Since the use of autologous fat injections is not only clinically approved but also much more convenient for a clinical approach, it is of utmost interest to know if both injection methods have a sufficient treatment effect on osteoarthritis.
