Characterization of progenitor cells derived from torn human rotator cuff tendons by gene expression patterns of chondro
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RESEARCH ARTICLE
Open Access
Characterization of progenitor cells derived from torn human rotator cuff tendons by gene expression patterns of chondrogenesis, osteogenesis, and adipogenesis Issei Nagura1,2*, Takeshi Kokubu2, Yutaka Mifune2, Atsuyuki Inui2, Fumiaki Takase2, Yasuhiro Ueda2, Takeshi Kataoka2 and Masahiro Kurosaka2
Abstract Background: It is important to regenerate the tendon-to-bone interface after rotator cuff repair to prevent re-tears. The cells from torn human rotator cuff were targeted, and their capacity for multilineage differentiation was investigated. Methods: The edges of the rotator cuff were harvested during arthroscopic rotator cuff repair from nine patients, minced into pieces, and cultured on dishes. Adherent cells were cultured, phenotypically characterized. Then expandability, differentiation potential and gene expression were analyzed. Results: Flow cytometry revealed that the mesenchymal stem cells (MSC)-related markers CD29, CD44, CD105, and CD166 were positive. However, CD14, CD34, and CD45 were negative. On RT-PCR analyses, the cells showed osteogenic, adipogenic, and chondrogenic potential after 3 weeks of culture under the respective differentiation conditions. In addition, SOX9, type II collagen, and type X collagen expression patterns during chondrogenesis were similar to those of endochondral ossification at the enthesis. Conclusions: The cells derived from torn human rotator cuff are multipotent mesenchymal stem cells with the ability to undergo multilineage differentiation, suggesting that MSCs form this tissue could be regenerative capacity for potential self-repair. Keywords: Human rotator cuff, Multilineage potential, Enthesis, Chondrogenic differentiation
Background Rotator cuff injuries are a commonly encountered cause of shoulder pain and dysfunction. Clinical results of rotator cuff repair have been good for both open and arthroscopic surgery [1, 2]. Despite advances in surgical technique over the past few decades, rotator cuff retears occur often after repair. The rate of occurrence of a re-tear is as low as 11 % [3] and as high as 94 % for * Correspondence: [email protected] 1 Department of Orthopaedic Surgery, Kobe Rosai Hospital, 4-1-23 Kagoike-dori, Chuo-ku, Kobe 651-0053, Japan 2 Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
large and massive rotator cuff repairs [4]. Rotator cuff repair depends on tendon-to-bone healing. In particular, fibrovascular scar tissue forms between the tendon and the bone after surgical repair and fails to regenerate the native enthesis [5]. This scar tissue is weaker than the normal rotator cuff insertion and may make repairs prone to failure [6–8]. In addition, differences in the biological environment at the intra-articular versus extra-articular regions contribute to the histological differences in tendon-bone healing [9]. The synovial fluid, which contains the antiadhesive protein lubricin, inhibits tendon-to-bone healing [10, 11]. The
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