Genetic modification of H2AX renders mesenchymal stromal cell–derived dopamine neurons more resistant to DNA damage and subsequent apoptosis

Peizhou Jiang, Peng Huang, Shu Hui Yen, Abba Zubair, Dennis W Dickson

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background aims Aberrant production of reactive oxygen species (ROS) and its impact on the integrity of genomic DNA have been considered one of the major risk factors for the loss of dopaminergic neurons in Parkinson's disease (PD). Stem cell transplantation as a strategy to replenish new functional neurons has great potential for PD treatment. However, limited survival of stem cells post-transplantation has always been an obstacle ascribed to the existence of neurotoxic environment in PD patients. Methods To improve the survival of transplanted stem cells for PD treatment, we explored a new strategy based on the function of the H2AX gene (H2A histone family, member X) in determination of DNA repair and cell apoptosis. We introduced a mutant form Y142F of H2AX into dopamine (DA) neuron-like cells differentiated from bone marrow–derived mesenchymal stromal cells (BMSCs). Results Expression of H2AX(Y142F) renders DA neuron-like cells more resistant to DNA damage and subsequent cell death induced by ultraviolet irradiation and 1-methyl-4-phenylpyridinium (MPP+) treatment. Discussion This is a meaningful attempt to improve the sustainability of BMSC-derived dopamine neurons under a brain neurotoxic environment. Further studies are needed to evaluate the implications of our findings in stem cell therapy for PD and related diseases.

Original languageEnglish (US)
Pages (from-to)1483-1492
Number of pages10
JournalCytotherapy
Volume18
Issue number12
DOIs
StatePublished - Dec 1 2016

Fingerprint

Dopaminergic Neurons
DNA Damage
Parkinson Disease
Apoptosis
Stem Cell Transplantation
Mesenchymal Stromal Cells
Stem Cells
1-Methyl-4-phenylpyridinium
Bone and Bones
Survival
Cell- and Tissue-Based Therapy
DNA Repair
Histones
Reactive Oxygen Species
Cell Death
Therapeutics
Neurons
DNA
Brain
Genes

Keywords

  • DNA damage
  • H2AX
  • lentivirus infection
  • mesenchymal stromal cells
  • Parkinson's disease

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Genetics(clinical)
  • Cell Biology
  • Cancer Research
  • Transplantation

Cite this

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title = "Genetic modification of H2AX renders mesenchymal stromal cell–derived dopamine neurons more resistant to DNA damage and subsequent apoptosis",
abstract = "Background aims Aberrant production of reactive oxygen species (ROS) and its impact on the integrity of genomic DNA have been considered one of the major risk factors for the loss of dopaminergic neurons in Parkinson's disease (PD). Stem cell transplantation as a strategy to replenish new functional neurons has great potential for PD treatment. However, limited survival of stem cells post-transplantation has always been an obstacle ascribed to the existence of neurotoxic environment in PD patients. Methods To improve the survival of transplanted stem cells for PD treatment, we explored a new strategy based on the function of the H2AX gene (H2A histone family, member X) in determination of DNA repair and cell apoptosis. We introduced a mutant form Y142F of H2AX into dopamine (DA) neuron-like cells differentiated from bone marrow–derived mesenchymal stromal cells (BMSCs). Results Expression of H2AX(Y142F) renders DA neuron-like cells more resistant to DNA damage and subsequent cell death induced by ultraviolet irradiation and 1-methyl-4-phenylpyridinium (MPP+) treatment. Discussion This is a meaningful attempt to improve the sustainability of BMSC-derived dopamine neurons under a brain neurotoxic environment. Further studies are needed to evaluate the implications of our findings in stem cell therapy for PD and related diseases.",
keywords = "DNA damage, H2AX, lentivirus infection, mesenchymal stromal cells, Parkinson's disease",
author = "Peizhou Jiang and Peng Huang and Yen, {Shu Hui} and Abba Zubair and Dickson, {Dennis W}",
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T1 - Genetic modification of H2AX renders mesenchymal stromal cell–derived dopamine neurons more resistant to DNA damage and subsequent apoptosis

AU - Jiang, Peizhou

AU - Huang, Peng

AU - Yen, Shu Hui

AU - Zubair, Abba

AU - Dickson, Dennis W

PY - 2016/12/1

Y1 - 2016/12/1

N2 - Background aims Aberrant production of reactive oxygen species (ROS) and its impact on the integrity of genomic DNA have been considered one of the major risk factors for the loss of dopaminergic neurons in Parkinson's disease (PD). Stem cell transplantation as a strategy to replenish new functional neurons has great potential for PD treatment. However, limited survival of stem cells post-transplantation has always been an obstacle ascribed to the existence of neurotoxic environment in PD patients. Methods To improve the survival of transplanted stem cells for PD treatment, we explored a new strategy based on the function of the H2AX gene (H2A histone family, member X) in determination of DNA repair and cell apoptosis. We introduced a mutant form Y142F of H2AX into dopamine (DA) neuron-like cells differentiated from bone marrow–derived mesenchymal stromal cells (BMSCs). Results Expression of H2AX(Y142F) renders DA neuron-like cells more resistant to DNA damage and subsequent cell death induced by ultraviolet irradiation and 1-methyl-4-phenylpyridinium (MPP+) treatment. Discussion This is a meaningful attempt to improve the sustainability of BMSC-derived dopamine neurons under a brain neurotoxic environment. Further studies are needed to evaluate the implications of our findings in stem cell therapy for PD and related diseases.

AB - Background aims Aberrant production of reactive oxygen species (ROS) and its impact on the integrity of genomic DNA have been considered one of the major risk factors for the loss of dopaminergic neurons in Parkinson's disease (PD). Stem cell transplantation as a strategy to replenish new functional neurons has great potential for PD treatment. However, limited survival of stem cells post-transplantation has always been an obstacle ascribed to the existence of neurotoxic environment in PD patients. Methods To improve the survival of transplanted stem cells for PD treatment, we explored a new strategy based on the function of the H2AX gene (H2A histone family, member X) in determination of DNA repair and cell apoptosis. We introduced a mutant form Y142F of H2AX into dopamine (DA) neuron-like cells differentiated from bone marrow–derived mesenchymal stromal cells (BMSCs). Results Expression of H2AX(Y142F) renders DA neuron-like cells more resistant to DNA damage and subsequent cell death induced by ultraviolet irradiation and 1-methyl-4-phenylpyridinium (MPP+) treatment. Discussion This is a meaningful attempt to improve the sustainability of BMSC-derived dopamine neurons under a brain neurotoxic environment. Further studies are needed to evaluate the implications of our findings in stem cell therapy for PD and related diseases.

KW - DNA damage

KW - H2AX

KW - lentivirus infection

KW - mesenchymal stromal cells

KW - Parkinson's disease

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