Human peripheral nerve xenografts and rat peripheral nerve allografts implanted to the striatum: Methodology and initial findings of cell-based therapy.

BACKGROUND

Peripheral nerve tissue engrafted into the central nervous system may provide regenerative effects in various CNS injury models or in a clinical trial using autologous sural nerve tissue grafts implanted into the substantia nigra of patients with Parkinson's disease (PD) as an adjuvant to Deep Brain Stimulation (DBS).

NEW METHOD: We describe a proof-of-concept neuro-avatar animal model to inform ongoing and future clinical trials and study the survival, biodistribution, and host responses to allografts or xenografts of human peripheral nerve fascicles. Human peripheral nerve tissue (PNT) was prepared as either injury-naïve or injured and then nerve fascicles were implanted into the rat naïve dorsal striatum or striatum pretreated with a fibril-seeding model of synucleinopathies.

RESULTS

At post-implantation, immunohistochemistry and MRI-imaging indicated both injury-naïve and injured nerve xenografts appeared to remain viable and stable at their implantation site with no evidence of nerve cell migration. Proton magnetic resonance spectroscopy of the xenografted brain identified increases in N-acetyl aspartate (NAA), a marker of neuronal integrity, in regions surrounding the xenograft. Preliminary RNAscope analysis of the xenografted brain indicates xenografts express mRNA for NGF and mitochondrial marker, ALDH2. Likewise, allografts of sciatic nerve implanted into the fibril-seeded brain were viable grafts 60 days after being placed into the degenerating brain and induced a sprouting response in the fibril-seeded brain.

CONCLUSION

We believe the neuro-avatar rodent model described in this study may be an asset for studying the possible regenerative effects of PNT engrafted into the degenerating brain.