Intra-articularly injected mesenchymal stem cells promote cartilage regeneration, but do not permanently engraft in distant organs
Intra-articularly injected mesenchymal stem cells promote cartilage regeneration, but do not permanently engraft in distant organs
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DOI：
10.1038/s41598-019-46554-5
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发表时间：
2019-07-12
影响因子：
4.6
通讯作者：
Erben, Reinhold G.
中科院分区：
文献类型：
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作者：
Satue, Maria;Schueler, Christiane;Erben, Reinhold G.
关节腔内注射间充质干细胞(MSCs)促进关节软骨修复。然而，移植后细胞的命运和作用仍不清楚。本研究旨在评价骨髓间充质干细胞在IA注射后的生物分布及疗效。我们使用了一种免疫活性的双转基因大鼠模型，该模型基于供体大鼠普遍表达热稳定的人胎盘碱性磷酸酶(ALPP)，受体大鼠表达热敏性ALPP形式。在受体大鼠的髌股沟处形成局灶性软骨缺损。将从供体大鼠分离的骨髓间充质干细胞注射到受体的滑膜腔内，并在注射后6个月以上对远端器官和膝关节进行细胞示踪。其中一例受者于注射后1d肺组织内可见少量供体MSCs。在后来的所有时间点，我们都未能在任何研究组织中检测到供体MSCs。注射IA的MSCs仍留在滑膜腔内，种植在软骨损伤内，直到注射后1个月仍可检测到。尽管MSCs的数量随着时间的推移而减少，但组织学和免疫荧光胶原染色表明，MSCs注射促进了软骨再生。我们的研究支持使用骨髓间充质干细胞通过IA输送进行软骨修复的安全性和有效性。
Intra-articular (IA) injection of mesenchymal stem cells (MSCs) promotes articular cartilage repair. However, cell fate and action after transplantation remain unclear. This study aimed at evaluating the biodistribution and efficacy of MSCs after IA injection. We used an immunocompetent, dual transgenic rat model, which is based on donor rats ubiquitously expressing heat stable human placental alkaline phosphatase (ALPP), and recipient rats expressing a heat sensitive ALPP form. A focal cartilage defect was created in the patellofemoral groove of recipient rats. Bone marrow-derived MSCs isolated from donor rats were injected into the synovial cavity of recipients, and cell tracking was performed in distant organs and knees over 6 months post-injection. A few donor MSCs were observed in the lung of one of the recipients, 1 day post-injection. We failed to detect donor MSCs in any of the studied tissues at all later time points. IA-injected MSCs remained in the synovial cavity, engrafted within the cartilage lesion, and were detectable up to 1 month post-injection. Although the number of MSCs decreased over time, MSCs injection promoted cartilage regeneration as evidenced by histology and immunofluorescent collagen staining. Our study supports the safety and efficacy of using MSCs for cartilage repair via IA delivery.