Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, NJ 08854, USA.
Ann Biomed Eng. 2013 Jun;41(6):1193-207. doi: 10.1007/s10439-013-0765-y. Epub 2013 Feb 22.
The spinal cord has a limited capacity to self-repair. After injury, endogenous stem cells are activated and migrate, proliferate, and differentiate into glial cells. The absence of neuronal differentiation has been partly attributed to the interaction between the injured microenvironment and neural stem cells. In order to improve post-injury neuronal differentiation and/or maturation potential, cell-cell and cell-biochemical interactions have been investigated. However, little is known about the role of stem cell-matrix interactions on stem cell-mediated repair. Here, we specifically examined the effects of matrix elasticity on stem cell-mediated repair in the spinal cord, since spinal cord injury results in drastic changes in parenchyma elasticity and viscosity. Spinal cord-derived neural precursor cells (NPCs) were grown on bis-acrylamide substrates with various rigidities. NPC growth, proliferation, and differentiation were examined and optimal in the range of normal spinal cord elasticity. In conclusion, limitations in NPC growth, proliferation, and neuronal differentiation were encountered when substrate elasticity was not within normal spinal cord tissue elasticity ranges. These studies elucidate the effect injury mediated mechanical changes may have on tissue repair by stem cells. Furthermore, this information can be applied to the development of future neuroregenerative biomaterials for spinal cord repair.
脊髓的自我修复能力有限。损伤后,内源性干细胞被激活并迁移、增殖和分化为神经胶质细胞。神经分化的缺失部分归因于损伤微环境与神经干细胞之间的相互作用。为了提高损伤后神经元的分化和/或成熟潜能,已经研究了细胞-细胞和细胞-生化相互作用。然而,关于干细胞-基质相互作用对干细胞介导的修复的作用知之甚少。在这里,我们特别研究了基质弹性对脊髓中干细胞介导修复的影响,因为脊髓损伤会导致实质弹性和粘度的急剧变化。脊髓源性神经前体细胞(NPC)在具有不同刚性的双丙烯酰胺基质上生长。检查 NPC 的生长、增殖和分化,并在正常脊髓弹性范围内最佳。总之,当基质弹性不在正常脊髓组织弹性范围内时,会遇到 NPC 生长、增殖和神经元分化的限制。这些研究阐明了损伤介导的机械变化可能对干细胞组织修复的影响。此外,这些信息可应用于开发用于脊髓修复的未来神经再生生物材料。