Sood Disha, Chwalek Karolina, Stuntz Emily, Pouli Dimitra, Du Chuang, Tang-Schomer Min, Georgakoudi Irene, Black Lauren D, Kaplan David L
Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford MA 02155, USA.
ACS Biomater Sci Eng. 2016;2(1):131-140. doi: 10.1021/acsbiomaterials.5b00446. Epub 2015 Dec 10.
The extracellular matrix (ECM) constituting up to 20% of the organ volume is a significant component of the brain due to its instructive role in the compartmentalization of functional microdomains in every brain structure. The composition, quantity and structure of ECM changes dramatically during the development of an organism greatly contributing to the remarkably sophisticated architecture and function of the brain. Since fetal brain is highly plastic, we hypothesize that the fetal brain ECM may contain cues promoting neural growth and differentiation, highly desired in regenerative medicine. Thus, we studied the effect of brain-derived fetal and adult ECM complemented with matricellular proteins on cortical neurons using 3D bioengineered model of cortical brain tissue. The tested parameters included neuronal network density, cell viability, calcium signaling and electrophysiology. Both, adult and fetal brain ECM as well as matricellular proteins significantly improved neural network formation as compared to single component, collagen I matrix. Additionally, the brain ECM improved cell viability and lowered glutamate release. The fetal brain ECM induced superior neural network formation, calcium signaling and spontaneous spiking activity over adult brain ECM. This study highlights the difference in the neuroinductive properties of fetal and adult brain ECM and suggests that delineating the basis for this divergence may have implications for regenerative medicine.
细胞外基质（ECM）占器官体积的20%，是大脑的重要组成部分，因为它在每个脑结构的功能微区划分中具有指导作用。在生物体发育过程中，ECM的组成、数量和结构会发生显著变化，这对大脑极其复杂的结构和功能有很大贡献。由于胎儿大脑具有高度可塑性，我们推测胎儿脑ECM可能含有促进神经生长和分化的线索，这在再生医学中是非常需要的。因此，我们使用皮质脑组织的3D生物工程模型，研究了补充基质细胞蛋白的胎儿和成人脑源性ECM对皮质神经元的影响。测试参数包括神经网络密度、细胞活力、钙信号传导和电生理学。与单一组分的I型胶原基质相比，成人和胎儿脑ECM以及基质细胞蛋白均显著改善了神经网络的形成。此外，脑ECM提高了细胞活力并降低了谷氨酸释放。与成人脑ECM相比，胎儿脑ECM诱导出更好的神经网络形成、钙信号传导和自发放电活动。这项研究突出了胎儿和成人脑ECM神经诱导特性的差异，并表明阐明这种差异的基础可能对再生医学有影响。
