Mesenchymal Stem Cells From a Hypoxic Culture Improve and Engraft Achilles Tendon Repair
Mesenchymal Stem Cells From a Hypoxic Culture Improve and Engraft Achilles Tendon Repair
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DOI：
10.1177/0363546513480786
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发表时间：
2013-05-01
影响因子：
4.8
通讯作者：
Hung, Shih-Chieh
中科院分区：
文献类型：
--
作者：
Huang, Tung-Fu;Yew, Tu-Lai;Hung, Shih-Chieh
背景资料：在低氧条件下培养的人骨髓间充质干细胞（MSCs）增加骨愈合能力。假设：在低氧条件下培养的大鼠MSCs在移植到受伤的跟腱后增加肌腱愈合潜力。研究设计：对照实验室研究。方法：生物力学测试，组织学分析，和溴脱氧尿苷（BrdU）标记/进行胶原免疫组织化学以证明与常氧MSC相比，用低氧MSC增强跟腱断裂部位增加愈合能力。MSC和对照。实验采用50只Sprague-Dawley大鼠，其中2只大鼠作为骨髓间充质干细胞来源。将大鼠的切断跟腱等分为3组：低氧MSC、常氧MSC和未处理（载体对照）。未切割肌腱作为正常未切割对照。结果测量包括24只大鼠的力学测试、组织学分析和另外24只大鼠的BrdU标记/胶原免疫组织化学。在切口后2周，低氧MSC组的极限破坏载荷显著大于未处理或常氧MSC组（分别为2.1 N/mm（2）vs 1.1 N/mm（2）或1.9 N/mm（2））和切开后4周（分别为5.5 N/mm（2）vs 1.7 N/mm（2）或2.7 N/mm（2））。低氧MSC组在切开后4周的极限破坏载荷（5.5 N/mm 2）接近但仍显著低于未切断肌腱的极限破坏载荷（7.2 N/mm 2）。通过半定量博纳尔组织病理学分级量表确定的组织学分析显示，与未处理或常氧MSC组相比，低氧MSC组在2周和4周时的跟腱愈合均得到显著改善。免疫组化进一步表明，缺氧和常氧MSC组有更强的免疫染色的I型和III型胶原比未处理组在2周和4周后切口。此外，注射前的骨髓间充质干细胞的BrdU标记进一步确定的掺入和保留的移植细胞在破裂situation.Conclusion：移植缺氧骨髓间充质干细胞可能是一个更好的和更容易获得的治疗比常氧骨髓间充质干细胞为跟腱rupture.Clinical Relevance：本研究提供的证据表明，移植缺氧骨髓间充质干细胞可能是一个有前途的治疗跟腱断裂。
Background: Bone marrow-derived mesenchymal stem cells (MSCs) from humans cultured under hypoxic conditions increase bone healing capacity.Hypothesis: Rat MSCs cultured under hypoxic conditions increase the tendon healing potential after transplantation into injured Achilles tendons.Study Design: Controlled laboratory study.Methods: Biomechanical testing, histological analysis, and bromodeoxyuridine (BrdU) labeling/collagen immunohistochemistry were performed to demonstrate that augmentation of an Achilles tendon rupture site with hypoxic MSCs increases healing capacity compared with normoxic MSCs and controls. Fifty Sprague-Dawley rats were used for the experiments, with 2 rats as the source of bone marrow MSCs. The cut Achilles tendons in the rats were equally divided into 3 groups: hypoxic MSC, normoxic MSC, and nontreated (vehicle control). The uncut tendons served as normal uncut controls. Outcome measures included mechanical testing in 24 rats, histological analysis, and BrdU labeling/collagen immunohistochemistry in another 24 rats.Results: The ultimate failure load in the hypoxic MSC group was significantly greater than that in the nontreated or normoxic MSC group at 2 weeks after incision (2.1 N/mm(2) vs 1.1 N/mm(2) or 1.9 N/mm(2), respectively) and at 4 weeks after incision (5.5 N/mm(2) vs 1.7 N/mm(2) or 2.7 N/mm(2), respectively). The ultimate failure load in the hypoxic MSC group at 4 weeks after incision (5.5 N/mm(2)) was close to but still significantly less than that of the uncut tendon (7.2 N/mm 2). Histological analysis as determined by the semi-quantitative Bonar histopathological grading scale revealed that the hypoxic MSC group underwent a significant improvement in Achilles tendon healing both at 2 and 4 weeks when compared with the nontreated or normoxic MSC group via statistical analysis. Immunohistochemistry further demonstrated that the hypoxic and normoxic MSC groups had stronger immunostaining for type I and type III collagen than did the nontreated group both at 2 and 4 weeks after incision. Moreover, BrdU labeling of MSCs before injection further determined the incorporation and retention of transplanted cells at the rupture site.Conclusion: Transplantation of hypoxic MSCs may be a better and more readily available treatment than normoxic MSCs for Achilles tendon ruptures.Clinical Relevance: The present study provides evidence that transplantation of hypoxic MSCs may be a promising therapy for the treatment of Achilles tendon ruptures.