Biomimetic Material-Assisted Delivery of Human Embryonic Stem Cell Derivatives for Enhanced In Vivo Survival and Engraftment.
Biomimetic Material-Assisted Delivery of Human Embryonic Stem Cell Derivatives for Enhanced In Vivo Survival and Engraftment.
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DOI：
10.1021/ab500021a
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发表时间：
2015-01-12
影响因子：
5.8
通讯作者：
Varghese S
中科院分区：
文献类型：
--
作者：
Kabra H;Hwang Y;Lim HL;Kar M;Arya G;Varghese S
人类胚胎干细胞（hESC）及其衍生物的分化和促进组织修复的能力具有治疗各种衰弱性疾病的巨大潜力。然而，提高移植细胞的体内活力和功能，这是将基于细胞的疗法转化为临床的关键决定因素，仍然是一项艰巨的任务。在这里，我们开发了一种混合生物材料，由透明质酸（HA）接枝6-氨基己酸部分（HA-6ACA），以改善细胞的交付和随后的体内功能，使用骨骼肌作为模型系统。我们的研究结果表明，仿生材料辅助的hESC衍生的肌源性祖细胞到NOD/SCID小鼠的心脏毒素损伤的骨骼肌中的递送以剂量依赖的方式显著促进移植细胞的存活和植入。发现供体细胞有助于受损肌纤维的再生和卫星细胞（肌肉特异性干细胞）隔室。这种具有成本效益且易于合成的仿生细胞递送载体可以在改善其他基于干细胞的疗法的结果方面发挥关键作用。
The ability of human embryonic stem cells (hESCs) and their derivatives to differentiate and contribute to tissue repair has enormous potential to treat various debilitating diseases. However, improving the in vivo viability and function of the transplanted cells, a key determinant of translating cell-based therapies to the clinic, remains a daunting task. Here, we develop a hybrid biomaterial consisting of hyaluronic acid (HA) grafted with 6-aminocaproic acid moieties (HA-6ACA) to improve cell delivery and their subsequent in vivo function using skeletal muscle as a model system. Our findings show that the biomimetic material-assisted delivery of hESC-derived myogenic progenitor cells into cardiotoxin-injured skeletal muscles of NOD/SCID mice significantly promotes survival and engraftment of transplanted cells in a dose-dependent manner. The donor cells were found to contribute to the regeneration of damaged muscle fibers and to the satellite cell (muscle specific stem cells) compartment. Such biomimetic cell delivery vehicles that are cost-effective and easy-to-synthesize could play a key role in improving the outcomes of other stem cell-based therapies.