The efficacy of lapine preconditioned or genetically modified IL4 over-expressing bone marrow-derived mesenchymal stromal cells in corticosteroid-associated osteonecrosis of the femoral head in rabbits.
The efficacy of lapine preconditioned or genetically modified IL4 over-expressing bone marrow-derived mesenchymal stromal cells in corticosteroid-associated osteonecrosis of the femoral head in rabbits.
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DOI：
10.1016/j.biomaterials.2021.120972
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发表时间：
2021-08
期刊：
影响因子：
14
通讯作者：
中科院分区：
文献类型：
--
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骨髓间充质干细胞（MSCs）用于增强髓芯减压（CD）的细胞治疗是治疗早期股骨头坏死（ONFH）的一种有前途的治疗方法。最近，已经描述了使用预处理的（具有促炎细胞因子）MSC（pMSC）或通过使用过表达抗炎细胞因子的MSC及时解决炎症来免疫调节成骨的治疗潜力。在这里，pMSCs暴露于肿瘤坏死因子-α和脂多糖3天加速体外成骨分化。此外，使用兔骨髓来源的MSC和兔皮质类固醇相关ONFH模型，将用可注射水凝胶包封的pMSC注射到骨隧道中促进体内股骨头中的血管生成和成骨。相反，体外和体内研究表明，通过使用在巨细胞病毒启动子下携带兔IL 4基因的慢病毒载体建立的过表达IL 4的遗传修饰的MSC（IL 4-MSC）加速了MSC的增殖并降低了股骨头中空陷窝的百分比。因此，使用pMSCs和IL 4-MSCs的CD的连续性细胞治疗可能有望治愈早期ONFH中的骨坏死病变。这些干预措施必须以时间敏感的方式应用，而不干扰骨愈合的强制性急性炎症阶段。
Cell-based therapy for augmentation of core decompression (CD) using mesenchymal stromal cells (MSCs) is a promising treatment for early stage osteonecrosis of the femoral head (ONFH). Recently, the therapeutic potential for immunomodulation of osteogenesis using preconditioned (with pro-inflammatory cytokines) MSCs (pMSCs), or by the timely resolution of inflammation using MSCs that over-express anti-inflammatory cytokines has been described. Here, pMSCs exposed to tumor necrosis factor-alpha and lipopolysaccharide for 3 days accelerated osteogenic differentiation in vitro. Furthermore, injection of pMSCs encapsulated with injectable hydrogels into the bone tunnel facilitated angiogenesis and osteogenesis in the femoral head in vivo, using rabbit bone marrow-derived MSCs and a model of corticosteroid-associated ONFH in rabbits. In contrast, in vitro and in vivo studies demonstrated that genetically-modified MSCs that over-express IL4 (IL4-MSCs), established by using a lentiviral vector carrying the rabbit IL4 gene under the cytomegalovirus promoter, accelerated proliferation of MSCs and decreased the percentage of empty lacunae in the femoral head. Therefore, adjunctive cell-based therapy of CD using pMSCs and IL4-MSCs may hold promise to heal osteonecrotic lesions in the early stage ONFH. These interventions must be applied in a temporally sensitive fashion, without interfering with the mandatory acute inflammatory phase of bone healing.
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影响因子：
5.6
作者：
Bastidas-Coral, Angela P.;Hogervorst, Jolanda M. A.;Bakker, Astrid D.
通讯作者：
Bakker, Astrid D.
影响因子：
3.3
作者：
Custodio, C. A.;Alves, C. M.;Mano, J. F.
通讯作者：
Mano, J. F.
DOI：
10.3109/15419069509081275
发表时间：
1995-01-01
期刊：
CELL ADHESION AND COMMUNICATION
影响因子：
--
作者：
AKIYAMA, SK;AOTA, S;YAMADA, KM
通讯作者：
YAMADA, KM
影响因子：
5.4
作者：
Fischer, JE;Johnson, JE;Graham, BS
通讯作者：
Graham, BS
影响因子：
12.4
作者：
Jiang, Yaping;Yu, Min;Wang, Jing
通讯作者：
Wang, Jing