Harnessing 3D collagen hydrogel-directed conversion of human GMSCs into SCP-like cells to generate functionalized nerve conduits.
Harnessing 3D collagen hydrogel-directed conversion of human GMSCs into SCP-like cells to generate functionalized nerve conduits.
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DOI：
10.1038/s41536-021-00170-y
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发表时间：
2021-09-30
影响因子：
7.2
通讯作者：
Le AD
中科院分区：
文献类型：
--
作者：
Zhang Q;Nguyen P;Burrell JC;Zeng J;Shi S;Shanti RM;Kulischak G;Cullen DK;Le AD
尽管显微外科技术不断进步，但严重周围神经损伤（PNI）后获得满意的功能恢复仍然是临床上的主要挑战之一。自体神经移植是目前治疗PNI的金标准，但存在几个主要的局限性。越来越多的证据表明，各种类型的神经引导导管（NGC）与作为支持细胞的出生后干细胞相结合，可能是神经自体移植的一种有希望的替代方案。在这项研究中，牙龈衍生的间充质干细胞（GMSC）在软胶原水凝胶中的3D培养下显示出与神经嵴干细胞样细胞（NCSC）和/或许旺细胞样细胞（SCP）的发育/分化相关的一组基因的表达显著增加，并与2D培养的对应物相比，与NOTCH 3信号通路激活相关。3D-胶原水凝胶诱导的NCSC相关基因的上调通过特异性NOTCH抑制剂的存在而被废除。进一步的研究表明，包埋在三维胶原水凝胶中的GMSC能够迁移到天然NGC的多层细胞外基质（ECM）壁中，并与对齐的基质结构良好地整合，从而导致功能化NGC的生物制造。在大鼠面神经节段性缺损模型中，植入负载GMSC衍生的NCSC/SCP样细胞（命名为GiSC）的功能化NGC显著改善了功能恢复和轴突再生。总之，我们的研究已经确定了一种通过利用GMSC向GiSC的3D胶原水凝胶定向转化来快速生物制造功能化NGC的方法。
Achieving a satisfactory functional recovery after severe peripheral nerve injuries (PNI) remains one of the major clinical challenges despite advances in microsurgical techniques. Nerve autografting is currently the gold standard for the treatment of PNI, but there exist several major limitations. Accumulating evidence has shown that various types of nerve guidance conduits (NGCs) combined with post-natal stem cells as the supportive cells may represent a promising alternative to nerve autografts. In this study, gingiva-derived mesenchymal stem cells (GMSCs) under 3D-culture in soft collagen hydrogel showed significantly increased expression of a panel of genes related to development/differentiation of neural crest stem-like cells (NCSC) and/or Schwann cell precursor-like (SCP) cells and associated with NOTCH3 signaling pathway activation as compared to their 2D-cultured counterparts. The upregulation of NCSC-related genes induced by 3D-collagen hydrogel was abrogated by the presence of a specific NOTCH inhibitor. Further study showed that GMSCs encapsulated in 3D-collagen hydrogel were capable of transmigrating into multilayered extracellular matrix (ECM) wall of natural NGCs and integrating well with the aligned matrix structure, thus leading to biofabrication of functionalized NGCs. In vivo, implantation of functionalized NGCs laden with GMSC-derived NCSC/SCP-like cells (designated as GiSCs), significantly improved the functional recovery and axonal regeneration in the segmental facial nerve defect model in rats. Together, our study has identified an approach for rapid biofabrication of functionalized NGCs through harnessing 3D collagen hydrogel-directed conversion of GMSCs into GiSCs.
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DOI：
10.1021/la502418s
发表时间：
2014-09-23
期刊：
Langmuir : the ACS journal of surfaces and colloids
影响因子：
--
作者：
Drzewiecki KE;Parmar AS;Gaudet ID;Branch JR;Pike DH;Nanda V;Shreiber DI
通讯作者：
Shreiber DI
影响因子：
4.8
作者：
Kaltschmidt, Barbara;Kaltschmidt, Christian;Widera, Darius
通讯作者：
Widera, Darius
影响因子：
5.2
作者：
Boddupally, Keerthi;Wang, Guangfang;Kobielak, Agnieszka
通讯作者：
Kobielak, Agnieszka
影响因子：
7.6
作者：
Khayat, A.;Monteiro, N.;Yelick, P. C.
通讯作者：
Yelick, P. C.
影响因子：
23.9
作者：
Kim, Yong Jun;Lim, Hotae;Lee, Gabsang
通讯作者：
Lee, Gabsang