To recruit or to graft? Comparing the recruitment of resident non-neuronal cells by lineage reprogramming with engraftment of stem cell-derived neurons for neuronal replacement therapies

Neurons are post-mitotic cells that are not replaced once lost, leading to the need for neuronal replacement therapies for central nervous system (CNS) repair. The generation of induced pluripotent stem cell (iPSC) derived human neurons is relatively advanced, with the capacity to generate pure and...

Full description

Saved in:
Bibliographic Details
Main Author: Daniel A. Peterson
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnins.2025.1589790/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849732747937972224
author Daniel A. Peterson
author_facet Daniel A. Peterson
author_sort Daniel A. Peterson
collection DOAJ
description Neurons are post-mitotic cells that are not replaced once lost, leading to the need for neuronal replacement therapies for central nervous system (CNS) repair. The generation of induced pluripotent stem cell (iPSC) derived human neurons is relatively advanced, with the capacity to generate pure and validated populations of different neuronal subtypes as clinical grade cells ready for engraftment. Clinical trials using human-derived embryonic stem cells (hESC) and iPSC-derived neurons are underway. As an alternative approach, the ability to target in vivo resident non-neuronal cells with reprogramming factors to induce replacement neurons has been demonstrated. The ability to engineer a defined population of resident replacement neurons that retain their cytoarchitectural location may permit an additional, more focused therapeutic strategy for specific circuits that could complement the bulk engraftment of ex vivo stem cell-derived replacement neurons. This mini-review summarizes and compares these two strategies and offers a perspective on the steps needed to advance recruitment as a complementary therapeutic strategy.
format Article
id doaj-art-e26ccf07a12f4ccb925020d77b40f10b
institution DOAJ
issn 1662-453X
language English
publishDate 2025-05-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Neuroscience
spelling doaj-art-e26ccf07a12f4ccb925020d77b40f10b2025-08-20T03:08:14ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-05-011910.3389/fnins.2025.15897901589790To recruit or to graft? Comparing the recruitment of resident non-neuronal cells by lineage reprogramming with engraftment of stem cell-derived neurons for neuronal replacement therapiesDaniel A. PetersonNeurons are post-mitotic cells that are not replaced once lost, leading to the need for neuronal replacement therapies for central nervous system (CNS) repair. The generation of induced pluripotent stem cell (iPSC) derived human neurons is relatively advanced, with the capacity to generate pure and validated populations of different neuronal subtypes as clinical grade cells ready for engraftment. Clinical trials using human-derived embryonic stem cells (hESC) and iPSC-derived neurons are underway. As an alternative approach, the ability to target in vivo resident non-neuronal cells with reprogramming factors to induce replacement neurons has been demonstrated. The ability to engineer a defined population of resident replacement neurons that retain their cytoarchitectural location may permit an additional, more focused therapeutic strategy for specific circuits that could complement the bulk engraftment of ex vivo stem cell-derived replacement neurons. This mini-review summarizes and compares these two strategies and offers a perspective on the steps needed to advance recruitment as a complementary therapeutic strategy.https://www.frontiersin.org/articles/10.3389/fnins.2025.1589790/fulllineage reprogrammingstem cell therapeuticscell graftinggene therapyneural repair and regenerationCNS repair
spellingShingle Daniel A. Peterson
To recruit or to graft? Comparing the recruitment of resident non-neuronal cells by lineage reprogramming with engraftment of stem cell-derived neurons for neuronal replacement therapies
Frontiers in Neuroscience
lineage reprogramming
stem cell therapeutics
cell grafting
gene therapy
neural repair and regeneration
CNS repair
title To recruit or to graft? Comparing the recruitment of resident non-neuronal cells by lineage reprogramming with engraftment of stem cell-derived neurons for neuronal replacement therapies
title_full To recruit or to graft? Comparing the recruitment of resident non-neuronal cells by lineage reprogramming with engraftment of stem cell-derived neurons for neuronal replacement therapies
title_fullStr To recruit or to graft? Comparing the recruitment of resident non-neuronal cells by lineage reprogramming with engraftment of stem cell-derived neurons for neuronal replacement therapies
title_full_unstemmed To recruit or to graft? Comparing the recruitment of resident non-neuronal cells by lineage reprogramming with engraftment of stem cell-derived neurons for neuronal replacement therapies
title_short To recruit or to graft? Comparing the recruitment of resident non-neuronal cells by lineage reprogramming with engraftment of stem cell-derived neurons for neuronal replacement therapies
title_sort to recruit or to graft comparing the recruitment of resident non neuronal cells by lineage reprogramming with engraftment of stem cell derived neurons for neuronal replacement therapies
topic lineage reprogramming
stem cell therapeutics
cell grafting
gene therapy
neural repair and regeneration
CNS repair
url https://www.frontiersin.org/articles/10.3389/fnins.2025.1589790/full
work_keys_str_mv AT danielapeterson torecruitortograftcomparingtherecruitmentofresidentnonneuronalcellsbylineagereprogrammingwithengraftmentofstemcellderivedneuronsforneuronalreplacementtherapies