Engineered mesenchymal stem cells with self-assembled vesicles for systemic cell targeting.
Engineered mesenchymal stem cells with self-assembled vesicles for systemic cell targeting.
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DOI：
10.1016/j.biomaterials.2010.03.006
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发表时间：
2010-07
期刊：
影响因子：
14
通讯作者：
Karp, Jeffrey M.
中科院分区：
文献类型：
--
作者：
Sarkar, Debanjan;Vemula, Praveen K.;Zhao, Weian;Gupta, Ashish;Karnik, Rohit;Karp, Jeffrey M.
细胞疗法有可能影响患者的生活质量。全身输注是一种方便的细胞递送方法;然而，植入的效率提出了一个重大挑战。已经表明，用粘附配体修饰细胞表面是改善细胞归巢的可行方法，然而包括遗传修饰的当前方法存在潜在的安全性问题，实际上是复杂的，并且不能适应多种归巢配体或不能适应多种细胞类型。我们在此报告了一种简便和通用的方法，使用脂质囊泡瞬时工程化细胞表面，以呈现促进细胞滚动的生物分子配体，这是归巢过程中的第一步之一。具体而言，我们证明了脂质囊泡与细胞膜快速融合，在细胞表面引入生物素部分，随后可以缀合链霉亲和素和潜在的任何生物素化归巢配体。鉴于细胞滚动是系统性细胞归巢的牢固粘附的先决条件，我们研究了在动态流动条件下，将唾液酸刘易斯X（SLeX）固定在间充质干细胞（MSC）上以诱导细胞在P-选择素表面上滚动的潜力。在剪切应力为0.5 dyn/cm 2时，SLeX修饰的MSC表现出明显改善的滚动相互作用，其速度为8 μm/s，而未修饰的MSC为61 μm/s。细胞表面修饰不影响MSC的表型，包括其活力和多谱系分化潜力。这些结果表明，用脂质囊泡对细胞表面的暂时修饰可用于有效地粘附粘附配体并潜在地将全身施用的细胞靶向至炎症部位。
Cell therapy has the potential to impact the quality of life of suffering patients. Systemic infusion is a convenient method of cell delivery; however, the efficiency of engraftment presents a major challenge. It has been shown that modification of the cell surface with adhesion ligands is a viable approach to improve cell homing, yet current methods including genetic modification suffer potential safety concerns, are practically complex and are unable to accommodate a wide variety of homing ligands or are not amendable to multiple cell types. We report herein a facile and generic approach to transiently engineer the cell surface using lipid vesicles to present biomolecular ligands that promote cell rolling, one of the first steps in the homing process. Specifically, we demonstrated that lipid vesicles rapidly fuse with the cell membrane to introduce biotin moieties on the cell surface that can subsequently conjugate streptavidin and potentially any biotinylated homing ligand. Given that cell rolling is a pre-requisite to firm adhesion for systemic cell homing, we examined the potential of immobilizing sialyl Lewis X (SLeX) on mesenchymal stem cells (MSCs) to induce cell rolling on a P-selectin surface, under dynamic flow conditions. MSCs modified with SLeX exhibit significantly improved rolling interactions with a velocity of 8 μm/s as compared to 61 μm/s for unmodified MSCs at a shear stress of 0.5 dyn/cm2. The cell surface modification does not impact the phenotype of the MSCs including their viability and multi-lineage differentiation potential. These results show that the transitory modification of cell surfaces with lipid vesicles can be used to efficiently immobilize adhesion ligands and potentially target systemically administered cells to the site of inflammation.
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影响因子：
4.7
作者：
Sarkar, Debanjan;Vemula, Praveen Kumar;Karp, Jeffrey M.
通讯作者：
Karp, Jeffrey M.
影响因子：
--
作者：
Jones, EA;Kinsey, SE;McGonagle, D
通讯作者：
McGonagle, D
影响因子：
37.8
作者：
Barbash, IM;Chouraqui, P;Leor, J
通讯作者：
Leor, J
影响因子：
2.4
作者：
Smith, CW
通讯作者：
Smith, CW
影响因子：
5.2
作者：
Brenner, S;Whiting-Theobald, N;Malech, HL
通讯作者：
Malech, HL