The Treatment Efficacy of Bone Tissue Engineering Strategy for Repairing Segmental Bone Defects Under Osteoporotic Conditions

The Treatment Efficacy of Bone Tissue Engineering Strategy for Repairing Segmental Bone Defects Under Osteoporotic Conditions
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骨质疏松条件下骨组织工程策略修复节段性骨缺损的治疗效果。

DOI:
10.1089/ten.tea.2015.0071
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发表时间:
2015-09-01
影响因子:
4.1
通讯作者:
Zhang, Wen Jie
Zhang, Wen Jie
中科院分区:
医学3区
文献类型:
--
作者:
Wang, Zhen Xing;Chen, Cheng;Zhang, Wen Jie

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利用干细胞治疗骨质疏松症增加骨量和预防骨折的潜力是目前的一个重点领域。然而,关于骨折后骨缺损在骨质疏松条件下愈合的有效性,现有的数据很少。本研究旨在探讨是否可以使用同种异体干细胞为基础的组织工程(TE)的方法修复骨质疏松症的兔模型中的临界尺寸的节段性骨缺损,并探讨骨质疏松症对治疗效果的潜在影响。体外扩增兔胎儿骨髓间充质干细胞(BMSCs)。然后将脱钙骨基质(DBM)支架与同种异体胎儿BMSC接种,并在成骨培养基中培养以工程化BMSC/DBM构建体。在卵巢切除(OVX)兔中产生临界尺寸的桡骨缺损,通过插入BMSC/DBM结构或单独使用DBM支架修复缺损。同时,年龄匹配的非卵巢切除(non-OVX)家兔作为对照。在骨质疏松条件下治疗后3个月(OVX兔),与DBM支架相比,插入缺损内的BMSC/DBM构建体产生了显著更多的骨组织,如X射线、显微计算机断层扫描和组织学分析所示。此外,与正常非骨质疏松状态(年龄匹配的非OVX兔)相比,骨缺损治疗效果受到骨质疏松状态的不利影响,骨再生显著减少。本研究证明了同种异体胎儿BMSC为基础的TE策略修复骨缺损在骨质疏松症的条件下的潜力。然而,在OVX动物中,治疗有效性可能会受到相当大的影响。因此,需要一种更复杂的策略来解决与骨质疏松症相关的复杂致病条件。
The potential of increasing bone mass and preventing fractures in osteoporosis using stem cell therapy is currently an area of intense focus. However, there are very little data available regarding the postfracture bony defect healing efficacy under osteoporotic conditions. This study aims to investigate whether critical-sized segmental bone defects in a rabbit model of osteoporosis could be repaired using an allogenic stem cell-based tissue engineering (TE) approach and to investigate the potential influence of osteoporosis on the treatment efficacy. Rabbit fetal bone marrow mesenchymal stem cells (BMSCs) were harvested and expanded in vitro. Decalcified bone matrix (DBM) scaffolds were then seeded with allogenic fetal BMSCs and cultivated in osteogenic media to engineer BMSC/DBM constructs. Critical-sized radial defects were created in ovariectomized (OVX) rabbits and the defects were repaired either by insertion of BMSC/DBM constructs or by DBM scaffolds alone. Also, nonovariectomized age-matched (non-OVX) rabbits were served as control. At 3 months post-treatment under the osteoporotic condition (OVX rabbits), the BMSC/DBM constructs inserted within the defect generated significantly more bone tissue when compared to the DBM scaffold as demonstrated by the X-ray, microcomputed tomography, and histological analyses. In addition, when compared to a normal nonosteoporotic condition (age-matched non-OVX rabbits), the defect treatment efficacy was adversely affected by the osteoporotic condition with significantly less bone regeneration. This study demonstrated the potential of allogenic fetal BMSC-based TE strategy for repairing bone defects in an osteoporotic condition. However, the treatment efficacy could be considerably compromised in the OVX animals. Therefore, a more sophisticated strategy that addresses the complicated pathogenic conditions associated with osteoporosis is needed.