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Cited by 18Mesenchymal stem cell researchPluripotent Stem Cells ResearchSpinal Cord Injury Research

Human iPSC-Derived MSCs induce neurotrophic effects and improve metabolic activity in acute neuronal injury models

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Kawatani, Keiji, Omana Suarez, Genesis, Perkerson, Ralph B., Parent, Ephraim E., Nambara, Toshihiko, Knight, Joshua A., Parsons, Tammee M., Gupta, Kshama +8 more·2025·The Journal of Neuroscience
DOI 10.1523/jneurosci.0606-24.2024PMC PMC11694398
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Abstract

Mesenchymal stromal cell (MSC) therapy has regenerative potentials to treat various pathological conditions including neurological diseases. MSCs isolated from various organs can differentiate into specific cell types to repair organ damages. However, their paracrine mechanisms are predicted to predominantly mediate their immunomodulatory, proangiogenic, and regenerative properties. While preclinical studies highlight the significant potential of MSC therapy in mitigating neurological damage from stroke and traumatic brain injury, the variability in clinical trial outcomes may stem from the inherent heterogeneity of somatic MSCs. Accumulating evidence has demonstrated that induced pluripotent stem cells (iPSCs) are an ideal alternative resource for the unlimited expansion and biomanufacturing of MSCs. Thus, we investigated how iPSC-derived MSCs (iMSCs) influence properties of iPSC-derived neurons. Our findings demonstrate that the secretome from iMSCs possesses neurotrophic effects, improving neuronal survival and promoting neuronal outgrowth and synaptic activity in vitro. Additionally, the iMSCs enhance metabolic activity via mitochondrial respiration in neurons, both in vitro and in mouse models. Glycolytic pathways also increased following the administration of iMSC secretome to iPSC-derived neurons. Consistently, in vivo experiments showed that intravenous administration of iMSCs compensated for the elevated energetic demand in male mice with irradiation-induced brain injury by restoring synaptic metabolic activity during acute brain damage. 18 F-FDG PET imaging also detected an increase in brain glucose uptake following iMSC administration. Together, our results highlight the potential of iMSC-based therapy in treating neuronal damage in various neurological disorders, while paving the way for future research and potential clinical applications of iMSCs in regenerative medicine.

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Authors
Kawatani, K., Omana Suarez, G., Perkerson, R. B., Parent, E. E., Nambara, T., Knight, J. A., Parsons, T. M., Gupta, K., Shue, F., Alnobani, A., Vibhute, P., Cai, H., Guerrero-Cázares, H., Copland, J. A., Quiñones-Hinojosa, A., & Kanekiyo, T.
Affiliations
Mayo Clinic (US)
Corresponding author
Kanekiyo, Takahisa
ORCID
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
2024-11-04
Volume
45
Issue
1
Pages
e0606242024
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
DOI
10.1523/jneurosci.0606-24.2024
PMC
PMC11694398
OpenAlex
W4404034925
Cited by
18
References
2
Citations by year
2026: 10 · 2025: 8
FWCI
5.05
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • HHS | NIH | National Institute on Aging (RF1AG068034, R01AG083981)
  • Mayo Clinic Center for Regenerative Biotherapeutics
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
Keywords
secretome, iPSC-derived neurons, neuronal survival, mitochondrial respiration, glycolysis, acute brain injury, synaptic activity, brain glucose uptake, 18F-FDG PET, stroke, traumatic brain injury, regenerative therapy
MeSH terms
Animals, Cell Differentiation, Cells, Cultured, Humans, Male, Mice, Inbred C57BL, Neurons, Mesenchymal Stem Cell Transplantation, Mice, Induced Pluripotent Stem Cells, Mesenchymal Stem Cells

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