Long-term survival of autologous peripheral nerve fascicles transplanted into the substantia nigra of participants with Parkinson disease: Preliminary observations

Cell transplantation therapies for Parkinson disease (PD) require confirmation that grafted tissue withstands the degenerative environment of the diseased brain. Autologous peripheral nerve tissue (PNT) grafts transplanted into the substantia nigra (SN) have been investigated in an ongoing clinical program, but characterization of graft survival after extended periods in the human CNS has been limited. We present histological and immunohistochemical analysis of PNT grafts in postmortem tissue from two participants who lived 7 years 11 months and 9 years 2 months following transplantation. Grafts persisted as structurally organized tissue with preserved fascicular architecture, compartmentalized boundaries defined by convergent GFAP-negative and COL1A1-positive demarcation, and cellular density comparable to naïve sural nerve. Immune cell presence within grafts was limited (4-7%) and concentrated at graft-host interfaces. Vascular networks including CD31-positive capillaries and SMA-positive arterioles were identified within grafts. Transplanted tissue maintained PNS identity with Schwann cell markers p75NTR, S100B, and MPZ detected within grafts, contrasting MBP expression in surrounding parenchyma. TH-positive processes within grafts, spatially associated with MPZ immunoreactivity, supported interactions between grafted Schwann cells and catecholaminergic processes consistent with dopaminergic origin. These findings provide histological evidence that autologous PNT grafts persist as organized, cellularly viable, transplanted tissue with maintained PNS identity after extended survival in the parkinsonian SN.