Biomimetic hydrogels direct spinal progenitor cell differentiation and promote functional recovery after spinal cord injury.
Biomimetic hydrogels direct spinal progenitor cell differentiation and promote functional recovery after spinal cord injury.
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DOI：
10.1088/1741-2552/aaa55c
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发表时间：
2018-04
影响因子：
4
通讯作者：
Schmidt CE
中科院分区：
文献类型：
--
作者：
Geissler SA;Sabin AL;Besser RR;Gooden OM;Shirk BD;Nguyen QM;Khaing ZZ;Schmidt CE
由疾病或创伤性损伤（如脊髓损伤（SCI））引起的脱髓鞘可能对神经功能和恢复产生破坏性影响。许多研究人员正在研究通过改善体内少突胶质细胞的可用性来减少脱髓鞘的治疗方法。干细胞和少突胶质细胞祖细胞的移植是一个有前途的选择，然而，试验受到无定向分化的困扰。在这里，我们介绍了一种生物材料，已被优化，以指导分化的神经祖细胞（NPC）向少突胶质细胞作为细胞输送车辆后SCI。胶原基水凝胶进行了修改，以模仿新生儿脊髓的机械性能，并在发展中的细胞外基质中存在的成分包括提供适当的化学线索的NPC，以指导其向少突胶质细胞分化。然后将含有细胞的水凝胶移植到SCI的单侧颈部挫伤模型中，以检查这种治疗的功能恢复。进行了六项行为测试和组织学评估，以检查对该处理的体内反应。我们的研究结果表明，我们可以实现一个显着增加少突胶质细胞分化的NPC相比，标准的培养条件下使用的三组分生物材料组成的胶原蛋白，透明质酸，和层粘连蛋白，具有机械性能匹配的新生儿神经组织。此外，有和没有NPC的水凝胶移植的SCI大鼠显示出功能恢复。与培养基对照组相比，用具有NPC的水凝胶移植的动物在6周内显示出显著增加的功能恢复。这里提出的三组分水凝胶有可能提供线索，在体内直接分化，以促进中枢神经系统的再生。
Demyelination that results from disease or traumatic injury, such as spinal cord injury (SCI), can have a devastating effect on neural function and recovery. Many researchers are examining treatments to minimize demyelination by improving oligodendrocyte availability in vivo. Transplantation of stem and oligodendrocyte progenitor cells is a promising option, however, trials are plagued by undirected differentiation. Here we introduce a biomaterial that has been optimized to direct the differentiation of neural progenitor cells (NPCs) toward oligodendrocytes as a cell delivery vehicle after SCI. A collagen-based hydrogel was modified to mimic the mechanical properties of the neonatal spinal cord, and components present in the developing extracellular matrix were included to provide appropriate chemical cues to the NPCs to direct their differentiation toward oligodendrocytes. The hydrogel with cells was then transplanted into a unilateral cervical contusion model of SCI to examine the functional recovery with this treatment. Six behavioral tests and histological assessment were performed to examine the in vivo response to this treatment. Our results demonstrate that we can achieve a significant increase in oligodendrocyte differentiation of NPCs compared to standard culture conditions using a three-component biomaterial composed of collagen, hyaluronic acid, and laminin that has mechanical properties matched to those of neonatal neural tissue. Additionally, SCI rats with hydrogel transplants, with and without NPCs, showed functional recovery. Animals transplanted with hydrogels with NPCs showed significantly increased functional recovery over 6 weeks compared to the media control group. The three-component hydrogel presented here has the potential to provide cues to direct differentiation in vivo to encourage regeneration of the central nervous system.
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DOI：
10.1016/j.bbagen.2014.01.021
发表时间：
2014-08-01
影响因子：
3
作者：
Bergstrom, Tobias;Holmqvist, Karin;Forsberg-Nilsson, Karin
通讯作者：
Forsberg-Nilsson, Karin
DOI：
10.1126/science.1171643
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Discher DE;Mooney DJ;Zandstra PW
通讯作者：
Zandstra PW
影响因子：
4.2
作者：
Chen K;Liu J;Assinck P;Bhatnagar T;Streijger F;Zhu Q;Dvorak MF;Kwon BK;Tetzlaff W;Oxland TR
通讯作者：
Oxland TR
影响因子：
14
作者：
Fuehrmann, T.;Tam, R. Y.;Shoichet, M. S.
通讯作者：
Shoichet, M. S.
影响因子：
4
作者：
Jagielska, Anna;Norman, Adele L.;Franklin, Robin J. M.
通讯作者：
Franklin, Robin J. M.