Human Adipose-Derived Stem Cells Accelerate the Restoration of Tensile Strength of Tendon and Alleviate the Progression of Rotator Cuff Injury in a Rat Model

Abstract

Adult stem cell therapy for the treatment of tendon injuries is a growing area of research. This study is aimed to investigate the efficacy of human adipose-derived stem cell (hADSC) injection on the tendon during its healing process in a rat model of rotator cuff injury. hADSCs were injected 3 days after collagenase-induced rotator cuff injuries in experimental groups, while the control group received saline as a placebo. Histological and biomechanical analyses were performed 7, 14, 21, and 28 days after collagenase injection. Compared to the control group, it was found that inflammatory cells were significantly decreased in the hADSC-treated group after collagenase injection for 7 and 14 days. In the hADSC-injected group, the fiber arrangement and tendon organization had also been improved. On the seventh day after collagenase injection, the load to failure of the hADSC-injected group (15.87 ± 2.20 N) was notably higher than that of the saline-injected group (11.20 ± 1.35 N). It is suggested that the tensile strength of the supraspinatus tendon was significantly enhanced. Local administration of hADSCs might have the possibility to restore the tensile strength and attenuate the progression of tendinitis. Taken together, these findings demonstrate that the recovery processes in damaged tendons can be facilitated architecturally and functionally after hADSC injection.

Adipose-Derived Regenerative Cells Promote Tendon-Bone Healing in a Rabbit Model

“…Adipose-derived regenerative cells (ADRCs) have multilineage potential equivalent to 38 bone marrow-derived stem cells and can be easily obtained in large amounts from subcutaneous 39 adipose tissue without the need for culture and expansion. 4,5 Although a number of reports have 40 been published regarding clinical applications of ADRCs, [6][7][8][9][10][11][12][13][14][15][16] we are unaware of any study 41 investigating ADRCs for their potential benefit in enhancing tendon graft healing in a bone tunnel. 42…”

Biologics and stem cell‐based therapies for rotator cuff repair

“…Although this model does not result in spontaneous tears, it remains the gold standard for inducing chronic rotator cuff tendon pathology. To chemically induce degeneration, collagenase can be injected directly into the supraspinatus tendon to degrade the collagen structure . Although collagenase treatment is experimentally less laborious and results in much more rapid changes to the tendon structure compared to the mechanical methods described above, this method is not commonly used since it does not recapitulate the clinical condition, which is largely mechanical in etiology.…”

“…Coculture of ASCs with macrophages suggests that ASCs can shift macrophages toward an anti‐inflammatory M2 phenotype and exert a protective effect on tendon fibroblasts . Delivery of ASCs to augment rotator cuff repair in vivo generally reduces inflammation and the presence of inflammatory cells; however, functional properties do not improve . Similarly, delivery of bMSCs showed increased numbers of anti‐inflammatory M2 macrophages at later timepoints, in parallel with upregulated enthesis markers .…”

Designing the stem cell microenvironment for guided connective tissue regeneration

“…These cells serve as a source of cytokines and proteinases essential to angiogenesis and tissue regeneration, including vascular endothelial growth factor (VEGF), matrix metalloproteinases, insulin‐like growth factor‐1 (IGF‐1), hepatocyte growth factor, TGF‐β, and basic fibroblast growth factor (bFGF) . Specific to connective tissues, MSCs promote functional healing within the tendon and tendon‐to‐bone interface through secretion of factors that stimulate fibroblast proliferation and angiogenesis, inhibit apoptosis, and minimize fibrosis …”

“…53 Specific to connective tissues, MSCs promote functional healing within the tendon and tendon-to-bone interface through secretion of factors that stimulate fibroblast proliferation and angiogenesis, inhibit apoptosis, and minimize fibrosis. 52,54,55 Given that stem cells have been identified in many tissues throughout the body, both mesenchymal and nonmesenchymal in origin, it is likely that common cell regulation features are shared among the MSC microenvironments. To understand the cues that are most critical for modulating stem cell response, novel model systems of the cell microenvironment have been developed and are highlighted in the following sections.…”