Abstract
Tendon repair is a medical challenge. Our present study investigated the effectiveness of acellular therapy consisting of conditioned medium (CM) of tendon stem cells (TSCs) induced with hepatocyte growth factor (HGF) in promoting the healing of injured Achilles tendon in a rat model. Proteomic analysis of soluble substances in the CM was performed using an array chip, and bioinformatic analysis was carried out to evaluate interactions among the factors. The effects of CM on viability and migratory capacity of tendon fibroblasts derived from rats with ruptured Achilles tendon were evaluated with the Cell Counting Kit 8 and wound healing assay, respectively. The expression of extracellular matrix (ECM)-related protein was assessed by western blotting. Rats with Achilles tendon injury were treated with CM by local injection for 2 weeks, and the organization of tendon fibers at the lesion site was evaluated by hematoxylin and eosin and Masson’s trichrome staining of tissue samples. The deposition and degradation of ECM proteins and the expression of inflammatory factors at the lesion site were evaluated by immunohistochemistry and immunofluorescence. Biomechanical testing was carried out on the injured tendons to assess functional recovery. There were 12 bioactive molecules in the CM, with HGF as the hub of the protein–protein interaction network. CM treatment enhanced the viability and migration of tendon fibroblasts, altered the expression of ECM proteins, promoted the organization of tendon fibers, suppressed inflammation and improved the biomechanics of the injured Achilles tendon. These results suggest that HGF stimulates the secretion of soluble secretory products by TSCs and CM promotes the repair and functional recovery of ruptured Achilles tendon. Thus, HGF-induced TSC CM has therapeutic potential for the treatment of tendinopathy.
Highlights
Tendons are prone to injury through tearing or rupture as they are overstretched during physical activity (Kannus and Natri, 1997)
Our results demonstrate that hepatocyte growth factor (HGF)-induced tendon stem cells (TSCs) conditioned medium (CM) is a novel acellular therapy that can facilitate the healing of injured tendon
We evaluated the effectiveness of the CM with the greatest therapeutic effect in all the above experiments [sections “Cell Counting Kit (CCK)-8,” “Wound healing assay,” “Western blotting,” “Immunohistochemistry analysis,” “Histological analysis,” and “Immunofluorescence analysis”] in promoting functional recovery in the rat model of Achilles tendon rupture
Summary
Tendons are prone to injury through tearing or rupture as they are overstretched during physical activity (Kannus and Natri, 1997). Unqualified repair can lead to long-term pain, discomfort, mobility impairment, and disability (Olsson et al, 2011; Gaspar et al, 2015; Braunstein et al, 2018). Various physical and biological interventions have been developed to improve the healing of injured tendons. Many stem cell (SC) types including mesenchymal (M)SCs derived from bone marrow (i.e., BMSCs) (Sharma and Snedeker, 2010; Yin et al, 2016; Veronesi et al, 2017), adipose tissue (Lee et al, 2017) and umbilical cord (Marmotti et al, 2018) were found to be effective in promoting tendon repair owing to their self-renewal capacity and multidifferentiation potential
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