Isolation and Characterization of 2 New Human Rotator Cuff and Long Head of Biceps Tendon Cells Possessing Stem Cell–Like Self-Renewal and Multipotential Differentiation Capacity

Randelli, Pietro; Conforti, Erika; Piccoli, Marco; Ragone, Vincenza; Creo, Pasquale; Cirillo, Federica; Masuzzo, Pamela; Tringali, Cristina; Cabitza, Paolo; Tettamanti, Guido; Gagliano, Nicoletta; Anastasia, Luigi

doi:10.1177/0363546512473572

Cited by 63 publications

(64 citation statements)

References 36 publications

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“…hTSCs were isolated from supraspinatus tendon of four adult donors (26 to 34 years old) undergoing arthroscopic rotator cuff repair as described previously [18]. The protocol for obtaining the tendon samples was approved by the Research Ethics Committee of Shanghai Sixth People's Hospital (Shanghai, China).…”

Section: Methodsmentioning

confidence: 99%

Autophagy Prevents Oxidative Stress-Induced Loss of Self-Renewal Capacity and Stemness in Human Tendon Stem Cells by Reducing ROS Accumulation

Chen

Ge²,

Wu³

et al. 2016

Cell Physiol Biochem

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Background/Aims: Tendon stem cells (TSCs) exhibit a high self-renewal capacity, multi-differentiation potential, and low immunogenicity; thus, these cells might provide a new cell source for tendon repair and regeneration. TSCs are exposed to increased oxidative stress at tendon injury sites; however, how TSCs maintain their stemness under oxidative stress is not clear. Methods and Results: In this study, we found that H₂O₂ treatment increased ROS accumulation in human TSCs (hTSCs) and resulted in loss of self-renewal capacity and stemness, as reflected in reduced colony formation and proliferation, decreased expression of the stemness markers Nanog, Oct-4, NS, and SSEA-4, and impaired differentiation capability. These H₂O₂-induced damages were prevented by pretreatment with starvation or rapamycin. Pretreatment with starvation or rapamycin prior to H₂O₂ exposure also led to decreased intracellular and mitochondrial ROS accumulation along with increased autophagic activity, as manifested in increased LC3 cleavage, Beclin-1 expression, and GFP-LC3-labeled autophagosome formation. Autophagy inhibition by 3-MA or CQ, or by shRNA silencing of Agt-7 or Beclin-1 reduced the protective effects of starvation and rapamycin on H₂O₂-treated hTSCs. Conclusion: Thus, the findings of this study suggest that autophagy prevents oxidative stress-induced loss of self-renewal capacity and stemness in hTSCs through suppression of ROS accumulation.

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Section: Methodsmentioning

confidence: 99%

Autophagy Prevents Oxidative Stress-Induced Loss of Self-Renewal Capacity and Stemness in Human Tendon Stem Cells by Reducing ROS Accumulation

Chen

Ge²,

Wu³

et al. 2016

Cell Physiol Biochem

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“…Specifically, platelet-derived GFs have been shown to improve rotator cuff healing (24), even though more clinical trials are necessary to show the real efficacy of these platelet concentrates in tendon healing. Promising future clinical therapeutic applications could also derive from the presence of stem cells in rotator cuff and long head biceps tendons (25). In conclusion, better knowledge of MMPs and TIMPs and more informed use of platelet concentrates and stem cells could open the way for a better strategy to optimize outcomes in rotator cuff tear therapy.…”

Section: J Ointsmentioning

confidence: 97%

Degenerative disease in rotator cuff tears: what are the biochemical and histological changes?

Giorgi¹

2014

jts

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The histopathological changes associated with rotator cuff tears include thinning and disorganization of collagen fibers, the presence of granulation tissue, increased levels of glycosaminoglycans, fibrocartilaginous metaplasia, calcification, fatty infiltration, and necrosis of the tendon margin with cell apoptosis. The biochemical changes include an increase in the expression of matrix metalloproteinases (MMPs) and a decrease in tissue inhibitor of metalloproteinases (TIMP) messenger ribonucleic acid expression. Histological evidence of tendinopathy has been found in patients with rotator cuff tear. Biochemical changes include significant increases in MMP1, MMP2, MMP3, and in TIMP1 and TIMP2 levels, not only at the lateral supraspinatus edge, but also in the macroscopically intact portion of the supraspinatus tendon and in the intact subscapularis. The tissue in the ruptured area of the supraspinatus tendon undergoes marked rearrangement at molecular levels. This involves the activity of MMP1, 2, and 3 and supports a critical role of MMPs in tendon physiology. Intact parts of the torn supraspinatus tendon can present the histopathological changes associated with rotator cuff tears. These findings suggest that biochemical changes can already occur in a macroscopically intact tendon and seem to point to a global degenerative process in the shoulder.Key Words: biology, histology, degenerative changes, rotator cuff tear.Rotator cuff tears are a frequent cause of shoulder pain and disability. The pathogenesis and the biochemical changes associated with rotator cuff tears are unclear, but they may arise from a combination of extrinsic impingement and intrinsic alterations within the tendon tissue itself (1). The etiology of rotator cuff disease is likely multifactorial, including age-related degeneration and microtrauma. Smoking, hypercholesterolemia and genetics have all been shown to influence the development of rotator cuff tearing (2). Tendons have a water content of 70%, while type I collagen accounts for 85% of their dry weight. Cells are scarce and those present are mostly (90-95%) fibroblasts. The histopathological changes associated with rotator cuff tears include thinning and disorganization of collagen fibers, the presence of granulation tissue, infiltration of glycosaminoglycans, fibrocartilaginous metaplasia, calcification, fatty degeneration, and necrosis of the tendon margin with cell apoptosis (3-5). These changes are also present in macroscopically intact tendons in the early stage of the degenerative process (3, 6). The degenerative changes at the tendon margin can also explain the high rate of recurrence after surgery, even in cases with less than grade 2 fatty infiltration (4). Chronic rotator cuff tears in elderly patients have limited healing potential and a high risk of recurrence, even if surgically treated. In these cases, the weak healing process seems to be produced more from the bursal side than from the tendinous one. Conversely, the healing potential of small and acute rotator c...

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“…Mesenchymal stem cells (MSCs) are used in tissue engineering and regenerative medicine applications for musculoskeletal tissue repair, particularly for their regenerative capabilities. MSCs can differentiate into tenocytes to promote tendon healing [2][3][4]. Engineered in vitro nanofiber scaffolds mimic the native topography of the extracellular matrix (ECM) microenvironmental cues that influence cell response and function including adhesion, migration, proliferation, and differentiation [5,6].…”

Section: Introductionmentioning

confidence: 99%

Aligned Nanofiber Topography Directs the Tenogenic Differentiation of Mesenchymal Stem Cells

2017

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Abstract:Tendon is commonly injured, heals slowly and poorly, and often suffers re-injury after healing. This is due to failure of tenocytes to effectively remodel tendon after injury to recapitulate normal architecture, resulting in poor mechanical properties. One strategy for improving the outcome is to use nanofiber scaffolds and mesenchymal stem cells (MSCs) to regenerate tendon. Various scaffold parameters are known to influence tenogenesis. We designed suspended and aligned nanofiber scaffolds with the hypothesis that this would promote tenogenesis when seeded with MSCs. Our aligned nanofibers were manufactured using the previously reported non-electrospinning Spinneret-based Tunable Engineered Parameters (STEP) technique. We compared parallel versus perpendicular nanofiber scaffolds with traditional flat monolayers and used cellular morphology, tendon marker gene expression, and collagen and glycosaminoglycan deposition as determinants for tendon differentiation. We report that compared with traditional control monolayers, MSCs grown on nanofibers were morphologically elongated with higher gene expression of tendon marker scleraxis and collagen type I, along with increased production of extracellular matrix components collagen (p = 0.0293) and glycosaminoglycan (p = 0.0038). Further study of MSCs in different topographical environments is needed to elucidate the complex molecular mechanisms involved in stem cell differentiation.

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Isolation and Characterization of 2 New Human Rotator Cuff and Long Head of Biceps Tendon Cells Possessing Stem Cell–Like Self-Renewal and Multipotential Differentiation Capacity

Cited by 63 publications

References 36 publications

Autophagy Prevents Oxidative Stress-Induced Loss of Self-Renewal Capacity and Stemness in Human Tendon Stem Cells by Reducing ROS Accumulation

Autophagy Prevents Oxidative Stress-Induced Loss of Self-Renewal Capacity and Stemness in Human Tendon Stem Cells by Reducing ROS Accumulation

Degenerative disease in rotator cuff tears: what are the biochemical and histological changes?

Aligned Nanofiber Topography Directs the Tenogenic Differentiation of Mesenchymal Stem Cells

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