Royal College of Surgeons in Ireland
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Neurotrophic extracellular matrix proteins promote neuronal and iPSC astrocyte progenitor cell- and nano-scale process extension for neural repair applications

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posted on 2025-01-14, 09:37 authored by Cian O' ConnorCian O' Connor, Rena MullallyRena Mullally, Sarah F McComish, Julia O'Sullivan, Ian WoodsIan Woods, Ingmar SchoenIngmar Schoen, Massimiliano GarreMassimiliano Garre, Maeve A Caldwell, Adrian DervanAdrian Dervan, Fergal O'BrienFergal O'Brien
The extracellular matrix plays a critical role in modulating cell behaviour in the developing and adult central nervous system influencing neural cell morphology, function and growth. Neurons and astrocytes, play vital roles in neural signalling and support respectively and respond to cues from the surrounding matrix environment. However, a better understanding of the impact of specific individual extracellular matrix proteins on both neurons and astrocytes is critical for advancing the development of matrix-based scaffolds for neural repair applications. This study aimed to provide an in-depth analysis of how different commonly used extracellular matrix proteins— laminin-1, Fn, collagen IV, and collagen I—affect the morphology and growth of trophic induced pluripotent stem cell (iPSC)-derived astrocyte progenitors and mouse motor neuron-like cells. Following a 7-day culture period, morphological assessments revealed that laminin-1, fibronectin, and collagen-IV, but not collagen I, promoted increased process extension and a stellate morphology in astrocytes, with collagen-IV yielding the greatest increases. Subsequent analysis of neurons grown on the different extracellular matrix proteins revealed a similar pattern with laminin-1, fibronectin, and collagen-IV supporting robust neurite outgrowth. fibronectin promoted the greatest increase in neurite extension, while collagen-I did not enhance neurite growth compared to poly-L-lysine controls. Super-resolution microscopy highlighted extracellular matrix-specific nanoscale changes in cytoskeletal organization, with distinct patterns of actin filament distribution where the three basement membrane-associated proteins (laminin-1, fibronectin, and collagen-IV) promoted the extension of fine cellular processes. Overall, this study demonstrates the potent effect of laminin-1, fibronectin and collagen-IV to promote both iPSC-derived astrocyte progenitor and neuronal growth, yielding detailed insights into the effect of extracellular matrix proteins on neural cell morphology at both the whole cell and nanoscale levels. The ability of laminin-1, collagen-IV and fibronectin to elicit strong growth-promoting effects highlight their suitability as optimal extracellular matrix proteins to incorporate into neurotrophic biomaterial scaffolds for the delivery of cell cargoes for neural repair.

Funding

Anatomical Society Student Fellowship

Physiological Society Professional Development Award

Microscopy Society of Ireland Training Bursary

Super-Resolution Imaging Consortium (SRIC)

Science Foundation Ireland

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Advanced Materials and BioEngineering Research Centre (AMBER)

Science Foundation Ireland

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History

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Comments

The original article is available at https://onlinelibrary.wiley.com/

Published Citation

O'Connor C, et al. Neurotrophic extracellular matrix proteins promote neuronal and iPSC astrocyte progenitor cell- and nano-scale process extension for neural repair applications. J Anat. 2024

Publication Date

28 October 2024

PubMed ID

39463075

Department/Unit

  • Tissue Engineering Research Group (TERG)
  • Anatomy and Regenerative Medicine
  • Amber (Advanced Material & Bioengineering Research) Centre
  • School of Pharmacy and Biomolecular Sciences
  • Chemistry

Research Area

  • Vascular Biology
  • Biomaterials and Regenerative Medicine
  • Chemistry and Pharmaceutical Sciences
  • Immunity, Infection and Inflammation

Publisher

Wiley

Version

  • Published Version (Version of Record)