A major cause of shoulder pain and dysfunction is attributed to rotator cuff tears. Following surgical repair, there is a high prevalence of tear re-occurrence due to failure of the supraspinatus tendon to fully heal. Researchers sought to investigate the use of microfragmented adipose tissue (MFAT) to enhance tendon cell viability, proliferation, and growth factor production in this in vitro human model. Their working hypothesis was that signaling among neighboring cells via the action of autologous MFAT would reduce the expression of harmful inflammatory markers in tendon cells derived from damaged tissue.
In this study, supraspinatus tendon biopsies and lipoaspirate adipose tissue were collected from 10 patients undergoing arthroscopic shoulder surgery. Tendon cells isolated from a torn supraspinatus tendon biopsy were cultured in a laboratory. A portion of the tendon cells were co-cultured with MFAT for 48 hours. Tendon cells cultured in the absence of MFAT served as the control. Cell viability, RNA and DNA isolation, and gene expression were all measured and analyzed with respect to cell markers, transcription factors, cytokine and chemokine production. Researchers observed that neither cell viability nor DNA of tendon cells was influenced by MFAT. This observation suggests that cell proliferation is not supported by MFAT application. There was no significant increase in the ratio of collagen type I to collagen type III expression. This observation suggests that the effect of MFAT in the context of tendon pathology is evidence for the prevention of tendon fibrosis. A reduction in MMP-3 enzyme expression was observed, but not in MMP-1 expression. High levels of MMP-3 are correlated with the incidence of tendon re-tear after rotator cuff repair; thus, a reduction of this catabolic enzyme expression supports the use of MFAT in conjunction with surgical rotator cuff repair to lessen tear re-occurence. Increases were observed in anti-inflammatory IL-1Ra cytokines and VEGF content, while levels of pro-inflammatory cytokine IL-1B were reduced.
Therefore, this study showed that MFAT effectively increased anti-inflammatory and trophic mediators in the media of tendon cells co-cultured with MFAT for 48 hours. Through the release of biochemical mediators among co-cultured cells in an in vitro model, the reduction of inflammatory, catabolic, and fibrotic cell marker expression was observed in tendon cells derived from an injured supraspinatus tendon. Higher levels of IL-1Ra, VEGF, and IL-6 that were observed in co-cultured media demonstrates anti-inflammatory mechanism and the promotion of tissue healing with the use of MFAT. Furthermore, this model demonstrates the application of regenerative medicine treatments as intended to counteract inflammatory processes in order to favor restoration of tissue homeostasis and healing, rather than increasing cell proliferation. Access the article here.