{
  "abstract": "Purpose\n\nDegradation 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\n\nWith 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\n\nTransplanted 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\n\nIntramuscular 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\n\nPreclinical controlled animal study, Level V.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Orthopedic Surgery, University of California, Irvine, CA.",
    "Department of Anatomy & Neurobiology, University of California, Irvine, CA.",
    "Reeve-Irvine Research Center, University of California, Irvine, CA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Luigi P Gonzales"
    },
    {
      "affs": [
        0
      ],
      "name": "Chris Lee"
    },
    {
      "affs": [
        0
      ],
      "name": "Arjun T Gupta"
    },
    {
      "affs": [
        0
      ],
      "name": "David J Wright"
    },
    {
      "affs": [
        0
      ],
      "name": "Tyler R Johnston"
    },
    {
      "affs": [
        0
      ],
      "name": "Sang Ho Yoon"
    },
    {
      "affs": [
        1
      ],
      "name": "Robert Hunt"
    },
    {
      "affs": [
        2
      ],
      "name": "Oswald Steward"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Ranjan Gupta"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b42addckx3kkt.bib",
  "cited_by": 0,
  "doi": "10.1016/j.jhsg.2026.101161",
  "fulltext_url": "https://europepmc.org/articles/PMC13679287",
  "id": "b42addckx3kkt",
  "issns": [
    "2589-5141"
  ],
  "landing_url": "https://europepmc.org/article/MED/42898828",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2804|Nerve injury and regeneration"
    ]
  ],
  "openalex": "W7221547554",
  "pdf_url": "https://europepmc.org/articles/PMC13679287?pdf=render",
  "pmcid": "PMC13679287",
  "pmid": "42898828",
  "published": "2026-10-12",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/b42addckx3kkt.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:33Z",
      "native_id": "MED:42898828",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42898828"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2804|Nerve injury and regeneration",
      "subfield": "neuroscience"
    }
  ],
  "title": "Human-Derived Motor Neuron Progenitor Cell Implantation Rescues Motor Endplates Following Peripheral Nerve Injury.",
  "title_text": "Human-Derived Motor Neuron Progenitor Cell Implantation Rescues Motor Endplates Following Peripheral Nerve Injury.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:33Z",
  "url": "https://research.draconitic.com/paper/b42addckx3kkt",
  "venue": "Journal of hand surgery global online",
  "versions": []
}