Morille Marie, Toupet Karine, Montero-Menei Claudia N, Jorgensen Christian, Noël Danièle
Inserm, U1183, Hôpital Saint-Eloi, Montpellier, F-34295, France; Université MONTPELLIER, UFR de Médecine, Montpellier, F-34000, France.
Inserm, U1066, Angers, F-44933, France; LUNAM University, Angers, F-49000, France.
Biomaterials. 2016 May;88:60-9. doi: 10.1016/j.biomaterials.2016.02.022. Epub 2016 Feb 18.
In the present study, we aimed at evaluating the ability of novel PLGA-P188-PLGA-based microspheres to induce the differentiation of mesenchymal stem/stromal cells (MSC) into chondrocytes. To this aim, we tested microspheres releasing TGFβ3 (PAM-T) in vitro and in situ, in a pathological osteoarthritic (OA) environment. We first evaluated the chondrogenic differentiation of human MSCs seeded onto PAM-T in vitro and confirmed the up-regulation of chondrogenic markers while the secretome of the cells was not changed by the 3D environment. We then injected human MSC seeded onto PAM-T in the knee joints of mice with collagenase-induced OA. After 6 weeks, histological analysis revealed that formation of a cartilage-like tissue occurred at the vicinity of PAM-T that was not observed when MSCs were seeded onto PAM. We also noticed that the endogenous articular cartilage was less degraded. The extent of cartilage protection was further analysed by confocal laser microscopy. When MSCs seeded onto PAM-T were injected early after OA induction, protection of cartilage against degradation was evidenced and this effect was associated to a higher survival of MSCs in presence of TGFβ3. This study points to the interest of using MSCs seeded onto PAM for cartilage repair and stimulation of endogenous cartilage regeneration.
在本研究中，我们旨在评估新型聚乳酸-聚乙醇酸共聚物-聚氧乙烯蓖麻油-聚乳酸-聚乙醇酸共聚物（PLGA-P188-PLGA）微球诱导间充质干/基质细胞（MSC）向软骨细胞分化的能力。为此，我们在体外和原位的病理性骨关节炎（OA）环境中测试了释放转化生长因子β3（TGFβ3）的微球（PAM-T）。我们首先评估了接种在PAM-T上的人MSC的软骨生成分化，并证实了软骨生成标志物的上调，而细胞的分泌组未因三维环境而改变。然后，我们将接种在PAM-T上的人MSC注射到胶原酶诱导的OA小鼠的膝关节中。6周后，组织学分析显示在PAM-T附近形成了类似软骨的组织，而当MSC接种在PAM上时未观察到这种情况。我们还注意到内源性关节软骨的降解较少。通过共聚焦激光显微镜进一步分析了软骨保护的程度。当在OA诱导后早期注射接种在PAM-T上的MSC时，证明了软骨对降解的保护作用，并且这种作用与在TGFβ3存在下MSC的更高存活率相关。这项研究指出了使用接种在PAM上的MSC进行软骨修复和刺激内源性软骨再生的意义。
