Evidence map›Paper›PMID 35449132›Full record

ArticleNPJ Regenerative medicine2022

Optimizing maturity and dose of iPSC-derived dopamine progenitor cell therapy for Parkinson's disease.

Benjamin M Hiller, David J Marmion, Cayla A Thompson, Nathaniel A Elliott, Howard Federoff, Patrik Brundin, Virginia B Mattis, Christopher W McMahon, Jeffrey H Kordower

Open access · goldAbstract read
In one paragraph

Article in NPJ Regenerative medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
5.5field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.

  1. Pooled it
  2. Taurochenodeoxycholic acid alleviates MPPIBRO neuroscience reports · 2026
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  9. Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Cell reprogramming: methods, mechanisms and applications.Cell regeneration (London, England) · 2025
    Review
  15. The Programme for Manufacture of hPSC‑Based Products for AMD and PD.Advances in experimental medicine and biology · 2025
    Review
  16. Review
  17. Review
  18. The history and status of dopamine cell therapies for Parkinson's disease.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Benjamin M HillerDepartment of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
David J MarmionDepartment of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.ORCID http://orcid.org/0000-0003-4575-2380
Cayla A ThompsonFUJIFILM Cellular Dynamics Inc., Madison, WI, USA.
Nathaniel A ElliottFUJIFILM Cellular Dynamics Inc., Madison, WI, USA.ORCID http://orcid.org/0000-0001-6749-5624
Howard FederoffBrooklyn ImmunoTherapeutics, Brooklyn, NY, USA.
Patrik BrundinParkinson's Disease Center, Department for Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI, USA.
Virginia B MattisFUJIFILM Cellular Dynamics Inc., Madison, WI, USA.ORCID http://orcid.org/0000-0001-5204-5604
Christopher W McMahonFUJIFILM Cellular Dynamics Inc., Madison, WI, USA.
Jeffrey H KordowerDepartment of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA. jeffrey.kordower@asu.edu.ORCID http://orcid.org/0000-0001-8629-3294
Rush University Medical Center · USEterna Therapeutics (United States) · USVan Andel Institute · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In pursuit of treating Parkinson's disease with cell replacement therapy, differentiated induced pluripotent stem cells (iPSC) are an ideal source of midbrain dopaminergic (mDA) cells. We previously established a protocol for differentiating iPSC-derived post-mitotic mDA neurons capable of reversing 6-hydroxydopamine-induced hemiparkinsonism in rats. In the present study, we transitioned the iPSC starting material and defined an adapted differentiation protocol for further translation into a clinical cell transplantation therapy. We examined the effects of cellular maturity on survival and efficacy of the transplants by engrafting mDA progenitors (cryopreserved at 17 days of differentiation, D17), immature neurons (D24), and post-mitotic neurons (D37) into immunocompromised hemiparkinsonian rats. We found that D17 progenitors were markedly superior to immature D24 or mature D37 neurons in terms of survival, fiber outgrowth and effects on motor deficits. Intranigral engraftment to the ventral midbrain demonstrated that D17 cells had a greater capacity than D24 cells to innervate over long distance to forebrain structures, including the striatum. When D17 cells were assessed across a wide dose range (7,500-450,000 injected cells per striatum), there was a clear dose response with regards to numbers of surviving neurons, innervation, and functional recovery. Importantly, although these grafts were derived from iPSCs, we did not observe teratoma formation or significant outgrowth of other cells in any animal. These data support the concept that human iPSC-derived D17 mDA progenitors are suitable for clinical development with the aim of transplantation trials in patients with Parkinson's disease.

Identifiers

PMID35449132
PMCPMC9023503
OpenAlexW4224254778

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.