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On-Chip Neural Induction Boosts Neural Stem Cell Commitment : Toward a Pipeline for iPSC-Based Therapies

Jain, Saumey ; Voulgaris, Dimitrios ; Thongkorn, Surangrat ; Hesen, Rick ; Hägg, Alice LU orcid ; Moslem, Mohsen ; Falk, Anna LU and Herland, Anna (2024) In Advanced science (Weinheim, Baden-Wurttemberg, Germany)
Abstract

The clinical translation of induced pluripotent stem cells (iPSCs) holds great potential for personalized therapeutics. However, one of the main obstacles is that the current workflow to generate iPSCs is expensive, time-consuming, and requires standardization. A simplified and cost-effective microfluidic approach is presented for reprogramming fibroblasts into iPSCs and their subsequent differentiation into neural stem cells (NSCs). This method exploits microphysiological technology, providing a 100-fold reduction in reagents for reprogramming and a ninefold reduction in number of input cells. The iPSCs generated from microfluidic reprogramming of fibroblasts show upregulation of pluripotency markers and downregulation of fibroblast... (More)

The clinical translation of induced pluripotent stem cells (iPSCs) holds great potential for personalized therapeutics. However, one of the main obstacles is that the current workflow to generate iPSCs is expensive, time-consuming, and requires standardization. A simplified and cost-effective microfluidic approach is presented for reprogramming fibroblasts into iPSCs and their subsequent differentiation into neural stem cells (NSCs). This method exploits microphysiological technology, providing a 100-fold reduction in reagents for reprogramming and a ninefold reduction in number of input cells. The iPSCs generated from microfluidic reprogramming of fibroblasts show upregulation of pluripotency markers and downregulation of fibroblast markers, on par with those reprogrammed in standard well-conditions. The NSCs differentiated in microfluidic chips show upregulation of neuroectodermal markers (ZIC1, PAX6, SOX1), highlighting their propensity for nervous system development. Cells obtained on conventional well plates and microfluidic chips are compared for reprogramming and neural induction by bulk RNA sequencing. Pathway enrichment analysis of NSCs from chip showed neural stem cell development enrichment and boosted commitment to neural stem cell lineage in initial phases of neural induction, attributed to a confined environment in a microfluidic chip. This method provides a cost-effective pipeline to reprogram and differentiate iPSCs for therapeutics compliant with current good manufacturing practices.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
differentiation, iPSC, Microfluidic chip, neural stem cell, reprogramming, stem cell therapy
in
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
article number
e2401859
pages
13 pages
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:85191185622
  • pmid:38655836
ISSN
2198-3844
DOI
10.1002/advs.202401859
project
IndiCell: Individualized pluripotent stemcell-based treatment
language
English
LU publication?
yes
additional info
© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.
id
cb55923c-c26f-4909-b8c1-e55f099662d6
date added to LUP
2024-04-26 13:56:43
date last changed
2024-06-18 18:57:03
@article{cb55923c-c26f-4909-b8c1-e55f099662d6,
  abstract     = {{<p>The clinical translation of induced pluripotent stem cells (iPSCs) holds great potential for personalized therapeutics. However, one of the main obstacles is that the current workflow to generate iPSCs is expensive, time-consuming, and requires standardization. A simplified and cost-effective microfluidic approach is presented for reprogramming fibroblasts into iPSCs and their subsequent differentiation into neural stem cells (NSCs). This method exploits microphysiological technology, providing a 100-fold reduction in reagents for reprogramming and a ninefold reduction in number of input cells. The iPSCs generated from microfluidic reprogramming of fibroblasts show upregulation of pluripotency markers and downregulation of fibroblast markers, on par with those reprogrammed in standard well-conditions. The NSCs differentiated in microfluidic chips show upregulation of neuroectodermal markers (ZIC1, PAX6, SOX1), highlighting their propensity for nervous system development. Cells obtained on conventional well plates and microfluidic chips are compared for reprogramming and neural induction by bulk RNA sequencing. Pathway enrichment analysis of NSCs from chip showed neural stem cell development enrichment and boosted commitment to neural stem cell lineage in initial phases of neural induction, attributed to a confined environment in a microfluidic chip. This method provides a cost-effective pipeline to reprogram and differentiate iPSCs for therapeutics compliant with current good manufacturing practices.</p>}},
  author       = {{Jain, Saumey and Voulgaris, Dimitrios and Thongkorn, Surangrat and Hesen, Rick and Hägg, Alice and Moslem, Mohsen and Falk, Anna and Herland, Anna}},
  issn         = {{2198-3844}},
  keywords     = {{differentiation; iPSC; Microfluidic chip; neural stem cell; reprogramming; stem cell therapy}},
  language     = {{eng}},
  month        = {{04}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Advanced science (Weinheim, Baden-Wurttemberg, Germany)}},
  title        = {{On-Chip Neural Induction Boosts Neural Stem Cell Commitment : Toward a Pipeline for iPSC-Based Therapies}},
  url          = {{http://dx.doi.org/10.1002/advs.202401859}},
  doi          = {{10.1002/advs.202401859}},
  year         = {{2024}},
}