Harnessing 3D collagen hydrogel-directed conversion of human GMSCs into SCP-like cells to generate functionalized nerve conduits

Loading...
Thumbnail Image
Penn collection
Departmental Papers (Dental)
Degree type
Discipline
Subject
Cell culture
Cell signaling
Collagen
Genes
Molecular biology
Neurons
Stem cells
5' nucleotidase
brain derived neurotrophic factor
cell surface marker
collagen
collagen gel
complementary DNA
cytoskeleton protein
dll1 protein
dll4 protein
epidermal growth factor receptor
erbb receptor feedback inhibitor 1
F actin
glial cell derived neurotrophic factor
glial cell line derived neurotrophic factor
glial fibrillary acidic protein
Hermes antigen
human insulin
hydrogel
inhibitor of differentiation 1
neurotrophic factor
Notch3 receptor
protein Jagged 2
protein p75
protein S100B
Thy 1 membrane glycoprotein
transcription factor Ets 1
transcription factor Ets 2
transcription factor HES 1
transcription factor HES 4
transcription factor hes 7
transcription factor hey 1
transcription factor jun
transcription factor Slug
transcription factor snail1
transcription factor Sox10
transcription factor Sox9
transcription factor tbx3
transcription factor Twist
unclassified drug
vinculin
Biofabrication
Functional recovery
Functionalized
Gold standards
Mesenchymal stem cell
Nerve conduits
Nerve injuries
Neural crests
Peripheral nerves
Schwann cells
animal cell
animal experiment
animal model
Article
cell differentiation
cell encapsulation
cell migration
comparative study
controlled study
extracellular matrix
facial nerve
facial nerve injury
female
gene expression
gingiva
gingiva derived mesenchymal stem cell
gingival tissue
human
human cell
human tissue
in vivo study
mesenchymal stem cell
muscle action potential
nerve conduction velocity
nerve fiber regeneration
neural crest cell
nonhuman
protein expression
rat
real time polymerase chain reaction
Schwann cell
signal transduction
three dimensional cell culture
two dimensional cell culture
upregulation
Hydrogels
Dentistry
Oral and Maxillofacial Surgery
Other Dentistry
Funder
Grant number
License
Copyright date
Distributor
Related resources
Author
Nguyen, Phuong
Burrell, Justin C
Zeng, Jincheng
Shi, Shihong
Shanti, Rabie M.
Kulischak, Grace
Cullen, D Kacy
Contributor
Abstract

Achieving a satisfactory functional recovery after severe peripheral nerve injuries (PNI) remains one of the major clinical challenges despite advances in microsurgical techniques. Nerve autografting is currently the gold standard for the treatment of PNI, but there exist several major limitations. Accumulating evidence has shown that various types of nerve guidance conduits (NGCs) combined with post-natal stem cells as the supportive cells may represent a promising alternative to nerve autografts. In this study, gingiva-derived mesenchymal stem cells (GMSCs) under 3D-culture in soft collagen hydrogel showed significantly increased expression of a panel of genes related to development/differentiation of neural crest stem-like cells (NCSC) and/or Schwann cell precursor-like (SCP) cells and associated with NOTCH3 signaling pathway activation as compared to their 2D-cultured counterparts. The upregulation of NCSC-related genes induced by 3D-collagen hydrogel was abrogated by the presence of a specific NOTCH inhibitor. Further study showed that GMSCs encapsulated in 3D-collagen hydrogel were capable of transmigrating into multilayered extracellular matrix (ECM) wall of natural NGCs and integrating well with the aligned matrix structure, thus leading to biofabrication of functionalized NGCs. In vivo, implantation of functionalized NGCs laden with GMSC-derived NCSC/SCP-like cells (designated as GiSCs), significantly improved the functional recovery and axonal regeneration in the segmental facial nerve defect model in rats. Together, our study has identified an approach for rapid biofabrication of functionalized NGCs through harnessing 3D collagen hydrogel-directed conversion of GMSCs into GiSCs. © 2021, The Author(s).

Advisor
Date Range for Data Collection (Start Date)
Date Range for Data Collection (End Date)
Digital Object Identifier
Series name and number
Publication date
2021-12-01
Journal title
npj Regenerative Medicine
Volume number
Issue number
Publisher
Publisher DOI
Journal Issue
Comments
Recommended citation
Collection