Cranial repair using BMP-2 gene engineered bone marrow stromal cells
Cranial repair using BMP-2 gene engineered bone marrow stromal cells
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DOI：
10.1016/j.jss.2003.08.003
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发表时间：
2004-06-01
影响因子：
2.2
通讯作者：
Lou, JR
中科院分区：
文献类型：
--
作者：
Chang, SCN;Chuang, HL;Lou, JR
背景。骨移植物、同种异体移植物和生物相容性人工骨替代物在用于修复颅骨缺损时均存在其缺点。组织工程骨有望作为修复这些缺陷的替代方案。材料和方法。植入前 1 个月，从髂嵴抽吸物中分离兔骨髓间充质基质细胞 (MSC)，并在单层培养物中扩增。然后在植入前 1 周，用复制缺陷型腺病毒-人 BMP-2 基因感染这些 MSC。通过去除骨诱导性骨膜和硬脑膜，在动物中产生双侧临界尺寸的颅骨缺损。将 MSC 与藻酸盐 UP（超纯）混合以形成 MSC/聚合物构建体。用于对照位点的 MSC 感染了腺病毒 β-半乳糖苷酶 (β-gal)。 1周、6周、3个月后，各实验组处死5只兔，对颅骨缺损部位进行组织学检查。结果。观察到使用组织工程 MSC/藻酸盐构建体几乎完全修复了大尺寸颅骨缺损。 H&E 染色和 von Kossa 染色应该可以更好地在实验部位再生骨骼。 BMP-2 治疗颅骨缺损后 3 个月时，3D CT 成像显示骨形成存在统计学显着性差异（0.79 +/- 0.06 与 0.47 +/- 0.05 cm(2)，p < 0.001），但在 6 周时则没有差异（0.36 +/- 0.04 与 0.33 +/- 0.03 cm(2)，P = 0.347).结论。使用组织工程骨可以实现大颅骨缺损的近乎完全修复。要实现这一目标，必须使用新开发的聚合物以及将干细胞概念与基因医学相结合。 (C) 2004 Elsevier Inc. 保留所有权利。
Background. Bone grafts, allografts, and biocompatible artificial bone substitutes all have their shortcomings when used for the repair of cranial bone defects. Tissue engineered bone shows promise as an alternative for the repair of these defects.Materials and methods. Rabbit bone marrow mesenchymal stromal cells (MSCs) were separated from iliac crest aspirates and expanded in a monolayer culture 1 month before implantation. These MSCs were then infected with replication-defective adenovirus-human BMP-2 genes 1 week before implantation. Bilateral critical-size cranial defects were created in the animal with removal of osteoinductive periosteum and dura. MSCs were mixed with alginate UP (ultrapure) to form MSC/polymer construct. MSCs used for the control site were infected with adenovirus beta-galactosidase (beta-gal). After 1 week, 6 weeks, and 3 months, five rabbits from each experimental group were sacrificed and the cranial defect site was examined by histology study.Results. Near-complete repair of the large size cranial defects using the tissue engineered MSC/alginate construct was observed. The H&E stain and von Kossa's staining should better regenerate bone at the experiment site. A statistically significant difference in bone formation was noted by 3D CT imaging at 3 months post-BMP-2 treatment of the cranial defects (0.79 +/- 0.06 versus 0.47 +/- 0.05 cm(2), p < 0.001) but not at 6 weeks (0.36 +/- 0.04 versus 0.33 +/- 0.03 cm(2), P = 0.347).Conclusions. Near-complete repair of large cranial defects can be achieved using tissue engineered bone. The use of newly developed polymers as well as the integration of the stem cell concept with gene medicine is necessary to attain this goal. (C) 2004 Elsevier Inc. All rights reserved.