Intra-articular delivery of purified mesenchymal stem cells from C57BL/6 or MRL/MpJ superhealer mice prevents posttraumatic arthritis.
Intra-articular delivery of purified mesenchymal stem cells from C57BL/6 or MRL/MpJ superhealer mice prevents posttraumatic arthritis.
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DOI：
10.3727/096368912x653264
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发表时间：
2013
影响因子：
3.3
通讯作者：
Guilak F
中科院分区：
文献类型：
--
作者：
Diekman BO;Wu CL;Louer CR;Furman BD;Huebner JL;Kraus VB;Olson SA;Guilak F
关节损伤显著增加了骨关节炎（OA）的发病率，估计占OA的12%。创伤后关节炎（PTA）在关节内骨折后尤其常见，目前尚无改善疾病的治疗方法。我们假设，间充质干细胞（MSC）的交付将通过改变小鼠膝关节骨折后炎症和再生的平衡来预防PTA。此外，我们检查了来自MRL/MpJ（MRL）“超级治疗者”小鼠品系的MSC与来自C57 BL/6（B6）小鼠的MSC相比将显示出增加的多谱系和治疗潜力的假设，因为MRL小鼠已经显示出异常的体内再生能力。使用细胞表面标志物（CD 45 −/TER 119 −/PDGFRα+/Sca-1+）从骨髓中前瞻性分离高度纯化的MSC群体。当在2%氧气下培养时，B6 MSC在三周内扩增超过100，000倍，并且与MRL MSC相比显示出更大的成脂、成骨和成软骨分化。骨折后仅接受对照盐水注射的小鼠在8周后表现出PTA，但向关节输送10，000个B6或MRL MSC阻止了PTA的发展。血清和滑液中的细胞因子水平受到干细胞治疗的影响，包括在几个时间点升高的全身性白细胞介素-10。骨髓间充质干细胞的输送并没有降低滑膜炎症的程度，但在修复过程中确实显示出骨体积的增加。这项研究提供了证据表明，关节内干细胞治疗可以预防骨折后PTA的发展，并对关节损伤后在明显OA证据出现之前可能的临床干预措施具有意义。
Joint injury dramatically enhances the onset of osteoarthritis (OA) and is responsible for an estimated 12% of OA. Post-traumatic arthritis (PTA) is especially common after intraarticular fracture, and no disease-modifying therapies are currently available. We hypothesized that the delivery of mesenchymal stem cells (MSCs) would prevent PTA by altering the balance of inflammation and regeneration after fracture of the mouse knee. Additionally, we examined the hypothesis that MSCs from the MRL/MpJ (MRL) “superhealer” mouse strain would show increased multilineage and therapeutic potentials as compared to those from C57BL/6 (B6) mice, as MRL mice have shown exceptional in vivo regenerative abilities. A highly purified population of MSCs was prospectively isolated from bone marrow using cell surface markers (CD45−/TER119−/PDGFRα+/Sca-1+). B6 MSCs expanded greater than 100,000 fold in three weeks when cultured at 2% oxygen and displayed greater adipogenic, osteogenic, and chondrogenic differentiation as compared to MRL MSCs. Mice receiving only a control saline injection after fracture demonstrated PTA after 8 weeks, but the delivery of 10,000 B6 or MRL MSCs to the joint prevented the development of PTA. Cytokine levels in serum and synovial fluid were affected by treatment with stem cells, including elevated systemic interleukin-10 at several time points. The delivery of MSCs did not reduce the degree of synovial inflammation but did show increased bone volume during repair. This study provides evidence that intra-articular stem cell therapy can prevent the development of PTA after fracture and has implications for possible clinical interventions after joint injury before evidence of significant OA.