仿生水凝胶指导脊髓祖细胞分化，促进脊髓损伤后的功能恢复。
Biomimetic hydrogels direct spinal progenitor cell differentiation and promote functional recovery after spinal cord injury.
机构信息
Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, United States of America. J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, United States of America.
出版信息
J Neural Eng. 2018 Apr;15(2):025004. doi: 10.1088/1741-2552/aaa55c.
OBJECTIVE
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.
APPROACH
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.
MAIN RESULTS
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 six weeks compared to the media control group.
SIGNIFICANCE
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.
目的
疾病或创伤（如脊髓损伤 [SCI]）导致的脱髓鞘对神经功能和恢复有毁灭性影响。许多研究人员正在研究通过提高体内少突胶质细胞的可用性来最小化脱髓鞘的治疗方法。干细胞和少突胶质前体细胞的移植是一种很有前途的选择，但试验受到未定向分化的困扰。在这里，我们引入了一种生物材料，该材料经过优化可作为 SCI 后细胞输送载体，将神经祖细胞（NPC）定向分化为少突胶质细胞。
方法
对基于胶原蛋白的水凝胶进行修饰，使其模仿新生脊髓的机械性能，并包含发育中细胞外基质中的成分，为 NPC 提供适当的化学线索，以将其分化为少突胶质细胞。然后将含有细胞的水凝胶移植到单侧颈挫伤 SCI 模型中，以检查该治疗的功能恢复情况。进行了六项行为测试和组织学评估，以检查该治疗的体内反应。
主要结果
我们的结果表明，与标准培养条件相比，我们可以使用由胶原蛋白、透明质酸和层粘连蛋白组成的三组分生物材料实现 NPC 中少突胶质细胞分化的显著增加，该生物材料具有与新生神经组织相匹配的机械性能。此外，具有和不具有 NPC 的水凝胶移植 SCI 大鼠表现出功能恢复。与培养基对照组相比，移植 NPC 水凝胶的动物在六周内表现出明显的功能恢复。
意义
这里提出的三组分水凝胶具有提供体内分化线索的潜力，以鼓励中枢神经系统的再生。
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