Human iPSC-derived neural progenitor cells secreting GDNF provide protection in rodent models of ALS and retinal degeneration

Stem Cell Reports. 2023 Aug 8;18(8):1629-1642. doi: 10.1016/j.stemcr.2023.03.016. Epub 2023 Apr 20.

Abstract

Human induced pluripotent stem cells (iPSCs) are a renewable cell source that can be differentiated into neural progenitor cells (iNPCs) and transduced with glial cell line-derived neurotrophic factor (iNPC-GDNFs). The goal of the current study is to characterize iNPC-GDNFs and test their therapeutic potential and safety. Single-nuclei RNA-seq show iNPC-GDNFs express NPC markers. iNPC-GDNFs delivered into the subretinal space of the Royal College of Surgeons rodent model of retinal degeneration preserve photoreceptors and visual function. Additionally, iNPC-GDNF transplants in the spinal cord of SOD1G93A amyotrophic lateral sclerosis (ALS) rats preserve motor neurons. Finally, iNPC-GDNF transplants in the spinal cord of athymic nude rats survive and produce GDNF for 9 months, with no signs of tumor formation or continual cell proliferation. iNPC-GDNFs survive long-term, are safe, and provide neuroprotection in models of both retinal degeneration and ALS, indicating their potential as a combined cell and gene therapy for various neurodegenerative diseases.

Keywords: ALS; CNS; Cell Therapy; GDNF; Human iPSC; Neurodegeneration; Retinitis Pigmentosa; Stem cell therapy; iPSC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis* / pathology
  • Animals
  • Astrocytes / pathology
  • Disease Models, Animal
  • Glial Cell Line-Derived Neurotrophic Factor / genetics
  • Humans
  • Induced Pluripotent Stem Cells* / pathology
  • Rats
  • Retinal Degeneration* / pathology
  • Retinal Degeneration* / therapy
  • Rodentia

Substances

  • Glial Cell Line-Derived Neurotrophic Factor