Injectable polypeptide hydrogels via methionine modification for neural stem cell delivery.
Injectable polypeptide hydrogels via methionine modification for neural stem cell delivery.
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DOI：
10.1016/j.biomaterials.2018.03.057
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发表时间：
2018-09
期刊：
影响因子：
14
通讯作者：
Deming TJ
中科院分区：
文献类型：
--
作者：
Wollenberg AL;O'Shea TM;Kim JH;Czechanski A;Reinholdt LG;Sofroniew MV;Deming TJ
具有可调节的理化和生物学特性的可注射水凝胶是改善神经干/祖细胞（NSPC）移植以治疗中枢神经系统（CNS）损伤和疾病的潜在工具。在这里，我们开发了用于 NSPC 移植的可注射二嵌段共聚肽水凝胶 (DCH)，其中含有修饰的 L-蛋氨酸 (Met) 的亲水片段。通过将 Met 聚合后修饰为各种功能衍生物，并将不同的氨基酸共聚单体掺入亲水链段，制备了多种基于 Met 的 DCH。基于 Met 的 DCH 组装成自修复水凝胶，具有浓度和成分依赖的机械性能。非离子甲亚砜制剂 (DCHMO) 的机械性能在不同的水介质中保持稳定，而阳离子制剂则表现出盐离子依赖性刚度降低。小鼠 NSPC 在 DCHMO 中的存活率与标准培养条件下的存活率相当，并且亚砜功能赋予细胞不污染特性。在体外富含血清的环境中，与细胞粘附材料相比，DCHMO 在保持 NSPC 干性和多能性方面更胜一筹。注入未受伤前脑的 DCHMO 中的 NSPC 仍保留在局部，4 周后，表现出不成熟的星形胶质细胞表型，与宿主神经组织整合，并充当支持宿主衍生轴突生长的细胞基质。这些发现表明，基于 Met 的 DCH 是进一步研究中枢神经系统损伤和疾病模型中 NSPC 移植的合适载体。
Injectable hydrogels with tunable physiochemical and biological properties are potential tools for improving neural stem/progenitor cell (NSPC) transplantation to treat central nervous system (CNS) injury and disease. Here, we developed injectable diblock copolypeptide hydrogels (DCH) for NSPC transplantation that contain hydrophilic segments of modified L-methionine (Met). Multiple Met-based DCH were fabricated by post-polymerization modification of Met to various functional derivatives, and incorporation of different amino acid comonomers into hydrophilic segments. Met-based DCH assembled into self-healing hydrogels with concentration and composition dependent mechanical properties. Mechanical properties of non-ionic Met-sulfoxide formulations (DCHMO) were stable across diverse aqueous media while cationic formulations showed salt ion dependent stiffness reduction. Murine NSPC survival in DCHMO was equivalent to that of standard culture conditions, and sulfoxide functionality imparted cell non-fouling character. Within serum rich environments in vitro, DCHMO was superior at preserving NSPC stemness and multipotency compared to cell adhesive materials. NSPC in DCHMO injected into uninjured forebrain remained local and, after 4 weeks, exhibited an immature astroglial phenotype that integrated with host neural tissue and acted as cellular substrates that supported growth of host-derived axons. These findings demonstrate that Met-based DCH are suitable vehicles for further study of NSPC transplantation in CNS injury and disease models.
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影响因子：
3.4
作者：
Deming, TJ
通讯作者：
Deming, TJ
影响因子：
5.5
作者：
Deming, TJ
通讯作者：
Deming, TJ
影响因子：
64.8
作者：
Falkner, Susanne;Grade, Sofia;Huebener, Mark
通讯作者：
Huebener, Mark
影响因子：
5.9
作者：
Ballios, Brian G.;Cooke, Michael J.;Donaldson, Laura;Coles, Brenda L. K.;Morshead, Cindi M.;van der Kooy, Derek;Shoichet, Molly S.
通讯作者：
Shoichet, Molly S.
星形胶质细胞疤痕形成有助于中枢神经系统轴突再生。
影响因子：
64.8
作者：
Anderson MA;Burda JE;Ren Y;Ao Y;O'Shea TM;Kawaguchi R;Coppola G;Khakh BS;Deming TJ;Sofroniew MV
通讯作者：
Sofroniew MV