Preprint
Long-term Connectivity between Spinal Cord Tissue Transplants and the Injured Phrenic Motor Network
bioRxiv
27 Jul 2026
PMID: 42619812
Abstract
Restoring vital motor functions after spinal cord injury (SCI) remains a central challenge in neuroscience and regenerative medicine. Cervical SCI can cause life-threatening respiratory deficits by damaging the phrenic motor network that controls the diaphragm. Cellular transplantation offers a viable means to improve function by providing new neurons that can relay supraspinal drive to denervated spinal phrenic networks, yet the long-term stability of transplants is poorly defined. Here, we examine donor-host neuronal synaptic connectivity in a respiratory model of cervical SCI, 1-year post-transplantation in adult rats. Embryonically-derived spinal cord tissue was transplanted into the lesion cavity one-week post-SCI, and transplant integration and diaphragm function were assessed at 1-month and 1-year post-transplantation. At 1-month, transplant-recipients exhibited significantly greater diaphragm output than injured, vehicle control animals. The extent of recovery at 1-year, however, was significantly less, coinciding with anatomical changes in graft neuronal density and donor-host connectivity, revealed by transneuronal tracing (pseudorabies virus). These results demonstrate that embryonic spinal cord transplants can improve phrenic motor activity after cervical SCI, but that long-term efficacy may be limited by reduced donor-host connectivity.
Cell transplantation can repair injured spinal cord circuits, but whether donor-host connections persist long term remains unclear. Using a rat model of cervical spinal cord injury, we show that embryonic spinal cord transplants improve diaphragm activity and integrate with the injured phrenic motor network at early time points, but these benefits decline by 1 year after transplantation. This loss of functional recovery is accompanied by reduced transneuronal labeling of donor neurons and changes in graft tissue composition. These results provide important proof of principle that transplant-host connectivity can be evaluated over extended survival times and identify long-term stability of donor-host integration as a critical challenge for achieving durable respiratory repair after spinal cord injury.
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Details
- Title
- Long-term Connectivity between Spinal Cord Tissue Transplants and the Injured Phrenic Motor Network
- Creators
- Adam A. Hall - Drexel UniversityLyandysha V. Zholudeva - Gladstone InstitutesTheresa Connors - Drexel UniversityVictoria Spruance - Drexel UniversityTara Fortino - Department of Neurobiology & Anatomy, Drexel University College of MedicineKayla Schardien - Department of Neurobiology & Anatomy, Drexel University College of MedicineAlessia Niceforo - Marion Murray Spinal Cord Research Center, Drexel University College of MedicineKimberly J. Dougherty - Marion Murray Spinal Cord Research Center, Drexel University College of MedicineLiang Qiang - Marion Murray Spinal Cord Research Center, Drexel University College of MedicineMichael A. Lane - Marion Murray Spinal Cord Research Center, Drexel University College of Medicine
- Publication Details
- bioRxiv
- Publisher
- Cold Spring Harbor Laboratory
- Edition
- 1.1
- Number of pages
- 30
- Resource Type
- Preprint
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Other Identifier
- 991022203443804721