Hydrogel and neural progenitor cell delivery supports organotypic fetal spinal cord development in an ex vivo model of prenatal spina bifida repair

水凝胶和神经祖细胞输送支持产前脊柱裂修复体外模型中的器官型胎儿脊髓发育

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作者:Juan C Biancotti, Kendal A Walker, Guihua Jiang, Julie Di Bernardo, Lonnie D Shea, Shaun M Kunisaki

Abstract

Studying how the fetal spinal cord regenerates in an ex vivo model of spina bifida repair may provide insights into the development of new tissue engineering treatment strategies to better optimize neurologic function in affected patients. Here, we developed hydrogel surgical patches designed for prenatal repair of myelomeningocele defects and demonstrated viability of both human and rat neural progenitor donor cells within this three-dimensional scaffold microenvironment. We then established an organotypic slice culture model using transverse lumbar spinal cord slices harvested from retinoic acid-exposed fetal rats to study the effect of fibrin hydrogel patches ex vivo. Based on histology, immunohistochemistry, gene expression, and enzyme-linked immunoabsorbent assays, these experiments demonstrate the biocompatibility of fibrin hydrogel patches on the fetal spinal cord and suggest this organotypic slice culture system as a useful platform for evaluating mechanisms of damage and repair in children with neural tube defects.

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