Neural precursor cells form integrated brain-like tissue when implanted into rat cerebrospinal fluid

Nikorn Pothayee,Jung-Hwa Tao-Cheng,Nadia Bouraoud,Stephen Dodd,Alan Koretsky,James Pickel,Alec Calac,Kathryn Sharer,Dragan Maric

doi:10.1038/s42003-018-0113-8

Abstract

There is tremendous interest in transplanting neural precursor cells for brain tissue regeneration. However, it remains unclear whether a vascularized and integrated complex neural tissue can be generated within the brain through transplantation of cells. Here, we report that early stage neural precursor cells recapitulate their seminal properties and develop into large brain-like tissue when implanted into the rat brain ventricle. Whereas the implanted cells predominantly differentiated into glutamatergic neurons and astrocytes, the host brain supplied the intact vasculature, oligodendrocytes, GABAergic interneurons, and microglia that seamlessly integrated into the new tissue. Furthermore, local and long-range axonal connections formed mature synapses between the host brain and the graft. Implantation of precursor cells into the CSF-filled cavity also led to a formation of brain-like tissue that integrated into the host cortex. These results may constitute the basis of future brain tissue replacement strategies.

Highlights

There is tremendous interest in transplanting neural precursor cells for brain tissue regeneration
Our experiments demonstrate that implanting early cortical neural precursor cells into the cerebrospinal fluid (CSF) space of the rat brain led to a remarkable proliferation and differentiation of precursor cells, forming large brain-like tissues that seamlessly attached and integrated with the host brain, without induction of glial scarring or eliciting an inflammatory response or graft rejection by the host
Green fluorescent protein (GFP)positive neural precursor cells lacking the surface phenotyping markers expressed by early glial or neuronal progenitors and their post-mitotic counterparts, as well as lacking markers expressed by resident non-neural cells, were isolated and enriched from E14 rat dorsal telencephalon dissociates using fluorescence activated cell sorting (FACS), as previously described[8] (Fig. 1a)

Summary

Introduction

There is tremendous interest in transplanting neural precursor cells for brain tissue regeneration. Implantation of precursor cells into the CSF-filled cavity led to a formation of brain-like tissue that integrated into the host cortex. Our experiments demonstrate that implanting early cortical neural precursor cells into the CSF space of the rat brain led to a remarkable proliferation and differentiation of precursor cells, forming large brain-like tissues that seamlessly attached and integrated with the host brain, without induction of glial scarring or eliciting an inflammatory response or graft rejection by the host. We show that brain-like tissue derived from cortical precursor cells could develop within a CSF-filled, injury-induced cavity in the cortex of adult rats and seamlessly integrated into the host brain, through the elimination of the glial scar, while generating extensive long-range axonal projections throughout the host brain

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Conclusion