Human-Derived Motor Neuron Progenitor Cell Implantation Rescues Motor Endplates Following Peripheral Nerve Injury.
- 1Department of Orthopedic Surgery, University of California, Irvine, CA.
- 2Department of Anatomy & Neurobiology, University of California, Irvine, CA.
- 3Reeve-Irvine Research Center, University of California, Irvine, CA.
Abstract
Purpose
Degradation of motor endplates (MEPs) following peripheral nerve injury (PNI) is a major determinant of functional recovery, as prolonged denervation renders target muscles progressively unreceptive to reinnervation. While prior studies have demonstrated that stem cell-based therapies may provide neurotrophic support following PNI, their potential effects on MEP preservation have not been well studied. We hypothesized that transplantation of human-induced pluripotent stem cell (hiPSC)-derived motor neuron progenitors (MNPs) into chronically denervated muscle would be associated with preservation of MEP architecture.Methods
With Institutional Animal Care and Use Committee approval, chronic denervation injuries were created in mice via sciatic nerve transection. After 4 months of denervation, when MEPs have consistently degraded in this animal model, the denervated tibialis anterior (TA) was injected with low-dose MNPs (10,000 cells), high-dose MNPs (500,000 cells), or phosphate-buffered saline (negative control). Using a previously established method, hiPSCs were differentiated into functional MNPs prior to injection. At selected time points post-injection, the TA was harvested and immunostained to confirm MNP viability and detect the presence of MEPs.Results
Transplanted MNPs remained viable within host muscle at both evaluated time points. No identifiable MEPs were detected in phosphate-buffered saline-treated chronically denervated muscle. In contrast, MNP-treated muscles demonstrated the presence of MEP-like structures following prolonged denervation. Qualitative differences in MEP density and morphologic complexity were observed between treatment groups, with greater preservation seen in the higher-dose cohort. Contralateral uninjured muscles demonstrated intact native MEP architecture.Conclusions
Intramuscular transplantation of hiPSC-derived MNPs into chronically denervated muscle was associated with preservation of MEP morphology in this preclinical proof-of-concept model. These preliminary findings suggest that cellular therapies may represent a potential adjunctive strategy to preserve end-organ receptivity following delayed peripheral nerve injury.Type of study/level of evidence
Preclinical controlled animal study, Level V.
Related
- Multilayered extracellular matrix derived scaffolds direct progenitor cell differentiation in vitro and osteochondral-tissue formation in vivo.
- Human CD34⁺ progenitor-derived DC2 and DC3 subsets support CD169-mediated HIV-1 uptake
- A rare pre-existing progenitor-like Primed SMC compartment is the dominant inferred source of SMC-derived cellularity in vascular injury and atherosclerosis
- Cannabis THC:CBD Composition Affects Oligodendrocyte Progenitor Cell Characteristics Following Acute Cannabis Vapor Inhalation in Adult Male and Female Mice
- Establishment of a cochlear lymphatic vascular network and immune surveillance system following cochlear implantation
BibTeX
@article{gonzales2026humanderived,
title = {{Human-Derived Motor Neuron Progenitor Cell Implantation Rescues Motor Endplates Following Peripheral Nerve Injury.}},
author = {Luigi P Gonzales and Chris Lee and Arjun T Gupta and David J Wright and Tyler R Johnston and Sang Ho Yoon and Robert Hunt and Oswald Steward and Ranjan Gupta},
journal = {Journal of hand surgery global online},
year = {2026},
month = oct,
doi = {10.1016/j.jhsg.2026.101161},
url = {https://europepmc.org/article/MED/42898828},
note = {CC BY},
}
RIS
TY - JOUR
TI - Human-Derived Motor Neuron Progenitor Cell Implantation Rescues Motor Endplates Following Peripheral Nerve Injury.
AU - Luigi P Gonzales
AU - Chris Lee
AU - Arjun T Gupta
AU - David J Wright
AU - Tyler R Johnston
AU - Sang Ho Yoon
AU - Robert Hunt
AU - Oswald Steward
AU - Ranjan Gupta
PY - 2026
DA - 2026/10/12
JO - Journal of hand surgery global online
DO - 10.1016/j.jhsg.2026.101161
UR - https://europepmc.org/article/MED/42898828
AB - Purpose Degradation of motor endplates (MEPs) following peripheral nerve injury (PNI) is a major determinant of functional recovery, as prolonged denervation renders target muscles progressively unreceptive to reinnervation. While prior studies have demonstrated that stem cell-based therapies may provide neurotrophic support following PNI, their potential effects on MEP preservation have not been well studied. We hypothesized that transplantation of human-induced pluripotent stem cell (hiPSC)-derived motor neuron progenitors (MNPs) into chronically denervated muscle would be associated with preservation of MEP architecture.Methods With Institutional Animal Care and Use Committee approval, chronic denervation injuries were created in mice via sciatic nerve transection. After 4 months of denervation, when MEPs have consistently degraded in this animal model, the denervated tibialis anterior (TA) was injected with low-dose MNPs (10,000 cells), high-dose MNPs (500,000 cells), or phosphate-buffered saline (negative control). Using a previously established method, hiPSCs were differentiated into functional MNPs prior to injection. At selected time points post-injection, the TA was harvested and immunostained to confirm MNP viability and detect the presence of MEPs.Results Transplanted MNPs remained viable within host muscle at both evaluated time points. No identifiable MEPs were detected in phosphate-buffered saline-treated chronically denervated muscle. In contrast, MNP-treated muscles demonstrated the presence of MEP-like structures following prolonged denervation. Qualitative differences in MEP density and morphologic complexity were observed between treatment groups, with greater preservation seen in the higher-dose cohort. Contralateral uninjured muscles demonstrated intact native MEP architecture.Conclusions Intramuscular transplantation of hiPSC-derived MNPs into chronically denervated muscle was associated with preservation of MEP morphology in this preclinical proof-of-concept model. These preliminary findings suggest that cellular therapies may represent a potential adjunctive strategy to preserve end-organ receptivity following delayed peripheral nerve injury.Type of study/level of evidence Preclinical controlled animal study, Level V.
SN - 2589-5141
ER -