Gene expression profiles of differentiated and undifferentiated adipose derived mesenchymal stem cells dynamically seeded onto a processed nerve allograft

Femke Mathot, Nadia Rbia, Roman Thaler, Allen T. Bishop, Andre J. Van Wijnen, Alexander Y. Shin

Research output: Contribution to journalArticle

Abstract

Background: Differentiation of mesenchymal stem cells (MSCs) into Schwann-like cells onto processed nerve allografts may support peripheral nerve repair. The purpose of this study was to understand the biological characteristics of undifferentiated and differentiated MSCs before and after seeding onto a processed nerve allograft by comparing gene expression profiles. Methods: MSCs from Lewis rats were cultured in maintenance media or differentiated into Schwann-like cells. Both treatment groups were dynamically seeded onto decellularized nerve allografts derived from Sprague-Dawley rats. Gene expression was quantified by quantitative polymerase chain reaction (qPCR) analysis of representative biomarkers, including neurotrophic (GDNF, PTN, GAP43, PMP22), angiogenic (CD31, VEGF1), extracellular matrix (ECM) (COL1A1, COL3A1, FBLN1, LAMB2) or cell cycle (CAPS3, CCBN2) genes. Gene expression values were statistically evaluated using a 2-factor ANOVA with repeated measures. Results: Baseline gene expression of undifferentiated and differentiated MSCs was significantly altered upon interaction with processed nerve allografts. Interaction between processed allografts and undifferentiated MSCs enhanced expression of neurotrophic (NGF, GDNF, PMP22), ECM (FBLN1, LAMB2) and regulatory cell cycle genes (CCNB2) during a 7-day time course. Interactions of differentiated MSCs with nerve allografts enhanced expression of neurotrophic (NGF, GDNF, GAP43), angiogenic (VEGF1), ECM (FBLN1) and regulatory cell cycle genes (CASP3, CCNB2) within one week. Conclusions: Dynamic seeding onto processed nerve allografts modulates temporal gene expression profiles of differentiated and undifferentiated MSCs. These changes in gene expressions may support the reparative functions of MSCs in supporting nerve regeneration in different stages of axonal growth.

Original languageEnglish (US)
Article number144151
JournalGene
Volume724
DOIs
StatePublished - Jan 15 2020

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Mesenchymal Stromal Cells
Transcriptome
Allografts
Glial Cell Line-Derived Neurotrophic Factor
Extracellular Matrix
Gene Expression
cdc Genes
Schwann Cells
Nerve Growth Factor
Regulator Genes
Nerve Regeneration
Peripheral Nerves
Caspase 3
Sprague Dawley Rats
Analysis of Variance
Cell Cycle
Biomarkers
Maintenance
Polymerase Chain Reaction
Growth

Keywords

  • Differentiation
  • Dynamic seeding
  • Peripheral nerve repair
  • qPCR
  • Schwann-like cells

ASJC Scopus subject areas

  • Genetics

Cite this

Gene expression profiles of differentiated and undifferentiated adipose derived mesenchymal stem cells dynamically seeded onto a processed nerve allograft. / Mathot, Femke; Rbia, Nadia; Thaler, Roman; Bishop, Allen T.; Van Wijnen, Andre J.; Shin, Alexander Y.

In: Gene, Vol. 724, 144151, 15.01.2020.

Research output: Contribution to journalArticle

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abstract = "Background: Differentiation of mesenchymal stem cells (MSCs) into Schwann-like cells onto processed nerve allografts may support peripheral nerve repair. The purpose of this study was to understand the biological characteristics of undifferentiated and differentiated MSCs before and after seeding onto a processed nerve allograft by comparing gene expression profiles. Methods: MSCs from Lewis rats were cultured in maintenance media or differentiated into Schwann-like cells. Both treatment groups were dynamically seeded onto decellularized nerve allografts derived from Sprague-Dawley rats. Gene expression was quantified by quantitative polymerase chain reaction (qPCR) analysis of representative biomarkers, including neurotrophic (GDNF, PTN, GAP43, PMP22), angiogenic (CD31, VEGF1), extracellular matrix (ECM) (COL1A1, COL3A1, FBLN1, LAMB2) or cell cycle (CAPS3, CCBN2) genes. Gene expression values were statistically evaluated using a 2-factor ANOVA with repeated measures. Results: Baseline gene expression of undifferentiated and differentiated MSCs was significantly altered upon interaction with processed nerve allografts. Interaction between processed allografts and undifferentiated MSCs enhanced expression of neurotrophic (NGF, GDNF, PMP22), ECM (FBLN1, LAMB2) and regulatory cell cycle genes (CCNB2) during a 7-day time course. Interactions of differentiated MSCs with nerve allografts enhanced expression of neurotrophic (NGF, GDNF, GAP43), angiogenic (VEGF1), ECM (FBLN1) and regulatory cell cycle genes (CASP3, CCNB2) within one week. Conclusions: Dynamic seeding onto processed nerve allografts modulates temporal gene expression profiles of differentiated and undifferentiated MSCs. These changes in gene expressions may support the reparative functions of MSCs in supporting nerve regeneration in different stages of axonal growth.",
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AU - Mathot, Femke

AU - Rbia, Nadia

AU - Thaler, Roman

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AU - Van Wijnen, Andre J.

AU - Shin, Alexander Y.

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