Programmable microencapsulation for enhanced mesenchymal stem cell persistence and immunomodulation
Programmable microencapsulation for enhanced mesenchymal stem cell persistence and immunomodulation
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DOI：
10.1073/pnas.1819415116
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发表时间：
2019-07-30
影响因子：
11.1
通讯作者：
Mooney, David J.
中科院分区：
文献类型：
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作者：
Mao, Angelo S.;Ozkale, Berna;Mooney, David J.
间充质干细胞（MSC）疗法在改善免疫失调疾病方面表现出特别的前景，但受到体内细胞持续时间短和表型不一致的阻碍。在这里，我们证明了使用微流体装置将生物材料包封到藻酸盐中可以显著增加静脉内（i.v.）注射细胞簇形成和随后与聚赖氨酸交联的组合导致注射的MSC半衰期增加超过一个数量级。这些修饰延长了持久性，即使在存在先天性和适应性免疫介导的清除。许可的封装MSC与炎性细胞因子移植前增加免疫调节相关基因的表达，并许可的封装物促进受体血液和骨髓与同种异体供体细胞亚致死照射后的2倍增加相似。微凝胶包封维持MSC存活和增加总体免疫调节能力的能力可适用于一般地改善MSC疗法。
Mesenchymal stem cell (MSC) therapies demonstrate particular promise in ameliorating diseases of immune dysregulation but are hampered by short in vivo cell persistence and inconsistencies in phenotype. Here, we demonstrate that biomaterial encapsulation into alginate using a microfluidic device could substantially increase in vivo MSC persistence after intravenous (i.v.) injection. A combination of cell cluster formation and subsequent cross-linking with polylysine led to an increase in injected MSC half-life by more than an order of magnitude. These modifications extended persistence even in the presence of innate and adaptive immunity-mediated clearance. Licensing of encapsulated MSCs with inflammatory cytokine pretransplantation increased expression of immunomodulatory-associated genes, and licensed encapsulates promoted repopulation of recipient blood and bone marrow with allogeneic donor cells after sublethal irradiation by a similar to 2-fold increase. The ability of microgel encapsulation to sustain MSC survival and increase overall immunomodulatory capacity may be applicable for improving MSC therapies in general.