Customized biomaterials to augment chondrocyte gene therapy.
Customized biomaterials to augment chondrocyte gene therapy.
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DOI：
10.1016/j.actbio.2017.02.008
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发表时间：
2017-04-15
影响因子：
9.7
通讯作者：
Bonassar LJ
中科院分区：
文献类型：
--
作者：
Aguilar IN;Trippel S;Shi S;Bonassar LJ
增强基因治疗的持续挑战是靶基因产物的瞬时可用性。这在组织工程应用中尤其如此。细胞短暂暴露于产品可能不足以促进组织再生。在这里，我们报告了一种新材料的开发，该材料被设计成对治疗性基因产物具有高亲和力。我们专注于胰岛素样生长因子-I（IGF-I）对许多组织如脊髓，心脏，大脑和软骨的高度合成代谢作用。组织储存IGF-I的方式之一是通过一组胰岛素样生长因子结合蛋白（IGFBP），如IGFBP-5。我们将来自IGFBP-5的IGF-I结合肽序列移植到藻酸盐上，以保留转染的软骨细胞产生的内源性IGF-I。这种新材料结合IGF-I并在培养物中释放生长因子至少30天。我们发现，这种结合增强了转染细胞的生物合成高达19倍。这些数据证明了细胞行为和材料化学的协调工程大大增强了细胞外基质合成和组织组装，并可作为其他治疗性蛋白质增强性能的模板。
A persistent challenge in enhancing gene therapy is the transient availability of the target gene product. This is particularly true in tissue engineering applications. The transient exposure of cells to the product could be insufficient to promote tissue regeneration. Here we report the development of a new material engineered to have a high affinity for a therapeutic gene product. We focus on insulin-like growth factor–I (IGF-I) for its highly anabolic effects on many tissues such as spinal cord, heart, brain and cartilage. One of the ways that tissues store IGF-I is through a group of insulin like growth factor binding proteins (IGFBPs), such as IGFBP-5. We grafted the IGF-I binding peptide sequence from IGFBP-5 onto alginate in order to retain the endogenous IGF-I produced by transfected chondrocytes. This novel material bound IGF-I and released the growth factor for at least 30 days in culture. We found that this binding enhanced the biosynthesis of transfected cells up to 19-fold. These data demonstrate the coordinated engineering of cell behavior and material chemistry to greatly enhance extracellular matrix synthesis and tissue assembly, and can serve as a template for the enhanced performance of other therapeutic proteins.
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DOI：
10.1302/0301-620x.89b5.18343
发表时间：
2007-05-01
影响因子：
--
作者：
Goodrich, L. R.;Hidaka, C.;Nixon, A. J.
通讯作者：
Nixon, A. J.
影响因子：
3.5
作者：
Kaul, G;Cucchiarini, M;Madry, H
通讯作者：
Madry, H
影响因子：
8
作者：
Hellgren, I;Drvota, V;Sylvén, C
通讯作者：
Sylvén, C
影响因子：
2.8
作者：
Bonassar, LJ;Grodzinsky, AJ;Trippel, SB
通讯作者：
Trippel, SB
影响因子：
2.9
作者：
KIM, YJ;SAH, RLY;GRODZINSKY, AJ
通讯作者：
GRODZINSKY, AJ