期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：26
页码：E3431-E3440
DOI：10.1073/pnas.1501835112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceCell transplantation can restore function in neurodegenerative disorders, but the low rate of functional integration of donor cells into host is a major limiting factor for clinical application. This problem is closely related to the long-standing view that donor cells must be transplanted intraneurally. We show that glial scar, which is common in neurodegenerative conditions, inhibits the survival of intraneurally transplanted cells in our rat glial scar model in the auditory system. However, cells placed on the surface of scar tissue autonomously enter the nerve and become functionally integrated into the host. The glial scar, normally considered to be a barrier to cell transplantation, includes important structural and chemical cues that are disrupted by intraneural delivery but preserved by surface transplantation. Cell transplantation therapy has long been investigated as a therapeutic intervention for neurodegenerative disorders, including spinal cord injury, Parkinson's disease, and amyotrophic lateral sclerosis. Indeed, patients have high hopes for a cell-based therapy. However, there are numerous practical challenges for clinical translation. One major problem is that only very low numbers of donor cells survive and achieve functional integration into the host. Glial scar tissue in chronic neurodegenerative disorders strongly inhibits regeneration, and this inhibition must be overcome to accomplish successful cell transplantation. Intraneural cell transplantation is considered to be the best way to deliver cells to the host. We questioned this view with experiments in vivo on a rat glial scar model of the auditory system. Our results show that intraneural transplantation to the auditory nerve, preceded by chondroitinase ABC (ChABC)-treatment, is ineffective. There is no functional recovery, and almost all transplanted cells die within a few weeks. However, when donor cells are placed on the surface of a ChABC-treated gliotic auditory nerve, they autonomously migrate into it and recapitulate glia- and neuron-guided cell migration modes to repair the auditory pathway and recover auditory function. Surface transplantation may thus pave the way for improved functional integration of donor cells into host tissue, providing a less invasive approach to rescue clinically important neural tracts.
