Enhanced In Vivo Delivery of Stem Cells using Microporous Annealed Particle Scaffolds
Enhanced In Vivo Delivery of Stem Cells using Microporous Annealed Particle Scaffolds
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DOI：
10.1002/smll.201903147
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发表时间：
2019-08-13
期刊：
影响因子：
13.3
通讯作者：
Di Carlo, Dino
中科院分区：
文献类型：
--
作者：
Koh, Jaekyung;Griffin, Donald R.;Di Carlo, Dino
递送至适当的组织隔室是阻碍细胞治疗剂用于医学病症的潜力的主要障碍。在生物材料内输送细胞可以改善定位，但传统和更新的空隙形成水凝胶必须在制造过程中预先将细胞添加到支架中。最近开发了可注射的原位交联微孔支架，其显示出在三维中为体外细胞增殖和生长提供基质的显著能力。这些支架在体内递送细胞的能力目前尚不清楚。在本文中，显示间充质干细胞（MSC）可以与注射后立即原位组装的微粒支架局部共注射。当与单独的细胞递送或传统的原位交联纳米多孔水凝胶内的递送相比时，微孔支架内的MSC递送增强了皮下MSC保留。两周后，形成血管的内皮细胞被募集到支架上，保留MSC标志物CD29的细胞在支架内保持活力。这些发现突出了这种方法在通过可注射多孔基质实现干细胞的局部递送中的效用，同时限制了在支架制造过程中引入细胞的障碍。
Delivery to the proper tissue compartment is a major obstacle hampering the potential of cellular therapeutics for medical conditions. Delivery of cells within biomaterials may improve localization, but traditional and newer void-forming hydrogels must be made in advance with cells being added into the scaffold during the manufacturing process. Injectable, in situ cross-linking microporous scaffolds are recently developed that demonstrate a remarkable ability to provide a matrix for cellular proliferation and growth in vitro in three dimensions. The ability of these scaffolds to deliver cells in vivo is currently unknown. Herein, it is shown that mesenchymal stem cells (MSCs) can be co-injected locally with microparticle scaffolds assembled in situ immediately following injection. MSC delivery within a microporous scaffold enhances MSC retention subcutaneously when compared to cell delivery alone or delivery within traditional in situ cross-linked nanoporous hydrogels. After two weeks, endothelial cells forming blood vessels are recruited to the scaffold and cells retaining the MSC marker CD29 remain viable within the scaffold. These findings highlight the utility of this approach in achieving localized delivery of stem cells through an injectable porous matrix while limiting obstacles of introducing cells within the scaffold manufacturing process.