Neuroprotective effect of human mesenchymal stem cells in an animal model of double toxin-induced multiple system atrophy parkinsonism

Hyun Jung Park, Giyoon Bang, Bo Ra Lee, Hyun Ok Kim, philhyu Lee

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Multiple system atrophy (MSA) is an adult-onset sporadic neurodegenerative disorder of unknown etiology featuring parkinsonism, ataxia, and autonomic failure in any combination. Because disease progression in MSA is rapid and no drug treatment consistently benefits MSA patients in the long term, neuroprotective or regenerative strategies may be invaluable in the management of MSA patients. In this study, we investigated whether human mesenchymal stem cells (hMSCs) had a protective effect on MSA using an animal model of double-toxin-induced MSA parkinsonism (MSA-P). MSA-P was established with coinjections of MPTP and 3-NP; hMSCs were injected into the tail vein 1 day after the last toxin injection. Three groups of mice were compared (i.e., control, MPTP + 3-NP, and MPTP + 3-NP with hMSC treatment) through histopathological, behavioral, and Western blot analyses. In the substantia nigra (SN) and the striatum, 2.0% and 3.8% of total injected hMSCs were observed, respectively. Compared with double-toxin-treated mice, hMSC treatment in double-toxin-treated mice significantly increased survival of TH-and NeuN-immunoreactive cells in the SN and the striatum, with coincident improvement in motor behavior. Additionally, hMSC treatment significantly decreased double-toxin-induced microglial and astroglial activation in the SN and striatum. Western blot analysis showed that hMSC administration in double-toxin-treated mice increased the expression of p-Akt and Bcl-2 and decreased Bax and cytochrome c expression. This study demonstrates that hMSC treatment protected against loss of neurons in the SN and the striatum induced by double toxin exposure, which may be mediated by modulation of inflammatory and cell survival and death signalingpathway as the hMSCs migrated from the peripheral circulation into the SN and striatum.

Original languageEnglish
Pages (from-to)827-835
Number of pages9
JournalCell transplantation
Volume20
Issue number6
DOIs
Publication statusPublished - 2011 Aug 22

Fingerprint

Multiple System Atrophy
Parkinsonian Disorders
Neuroprotective Agents
Stem cells
Mesenchymal Stromal Cells
Animals
Animal Models
Substantia Nigra
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Western Blotting
Drug therapy
Therapeutics
Ataxia
Cytochromes c
Neurodegenerative Diseases
Neurons
Disease Progression
Tail
Veins
Cell Survival

All Science Journal Classification (ASJC) codes

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

Cite this

@article{e025b7dcf8034f378cdd8409680ad06f,
title = "Neuroprotective effect of human mesenchymal stem cells in an animal model of double toxin-induced multiple system atrophy parkinsonism",
abstract = "Multiple system atrophy (MSA) is an adult-onset sporadic neurodegenerative disorder of unknown etiology featuring parkinsonism, ataxia, and autonomic failure in any combination. Because disease progression in MSA is rapid and no drug treatment consistently benefits MSA patients in the long term, neuroprotective or regenerative strategies may be invaluable in the management of MSA patients. In this study, we investigated whether human mesenchymal stem cells (hMSCs) had a protective effect on MSA using an animal model of double-toxin-induced MSA parkinsonism (MSA-P). MSA-P was established with coinjections of MPTP and 3-NP; hMSCs were injected into the tail vein 1 day after the last toxin injection. Three groups of mice were compared (i.e., control, MPTP + 3-NP, and MPTP + 3-NP with hMSC treatment) through histopathological, behavioral, and Western blot analyses. In the substantia nigra (SN) and the striatum, 2.0{\%} and 3.8{\%} of total injected hMSCs were observed, respectively. Compared with double-toxin-treated mice, hMSC treatment in double-toxin-treated mice significantly increased survival of TH-and NeuN-immunoreactive cells in the SN and the striatum, with coincident improvement in motor behavior. Additionally, hMSC treatment significantly decreased double-toxin-induced microglial and astroglial activation in the SN and striatum. Western blot analysis showed that hMSC administration in double-toxin-treated mice increased the expression of p-Akt and Bcl-2 and decreased Bax and cytochrome c expression. This study demonstrates that hMSC treatment protected against loss of neurons in the SN and the striatum induced by double toxin exposure, which may be mediated by modulation of inflammatory and cell survival and death signalingpathway as the hMSCs migrated from the peripheral circulation into the SN and striatum.",
author = "Park, {Hyun Jung} and Giyoon Bang and Lee, {Bo Ra} and Kim, {Hyun Ok} and philhyu Lee",
year = "2011",
month = "8",
day = "22",
doi = "10.3727/096368910X540630",
language = "English",
volume = "20",
pages = "827--835",
journal = "Cell Transplantation",
issn = "0963-6897",
publisher = "Cognizant Communication Corporation",
number = "6",

}

Neuroprotective effect of human mesenchymal stem cells in an animal model of double toxin-induced multiple system atrophy parkinsonism. / Park, Hyun Jung; Bang, Giyoon; Lee, Bo Ra; Kim, Hyun Ok; Lee, philhyu.

In: Cell transplantation, Vol. 20, No. 6, 22.08.2011, p. 827-835.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Neuroprotective effect of human mesenchymal stem cells in an animal model of double toxin-induced multiple system atrophy parkinsonism

AU - Park, Hyun Jung

AU - Bang, Giyoon

AU - Lee, Bo Ra

AU - Kim, Hyun Ok

AU - Lee, philhyu

PY - 2011/8/22

Y1 - 2011/8/22

N2 - Multiple system atrophy (MSA) is an adult-onset sporadic neurodegenerative disorder of unknown etiology featuring parkinsonism, ataxia, and autonomic failure in any combination. Because disease progression in MSA is rapid and no drug treatment consistently benefits MSA patients in the long term, neuroprotective or regenerative strategies may be invaluable in the management of MSA patients. In this study, we investigated whether human mesenchymal stem cells (hMSCs) had a protective effect on MSA using an animal model of double-toxin-induced MSA parkinsonism (MSA-P). MSA-P was established with coinjections of MPTP and 3-NP; hMSCs were injected into the tail vein 1 day after the last toxin injection. Three groups of mice were compared (i.e., control, MPTP + 3-NP, and MPTP + 3-NP with hMSC treatment) through histopathological, behavioral, and Western blot analyses. In the substantia nigra (SN) and the striatum, 2.0% and 3.8% of total injected hMSCs were observed, respectively. Compared with double-toxin-treated mice, hMSC treatment in double-toxin-treated mice significantly increased survival of TH-and NeuN-immunoreactive cells in the SN and the striatum, with coincident improvement in motor behavior. Additionally, hMSC treatment significantly decreased double-toxin-induced microglial and astroglial activation in the SN and striatum. Western blot analysis showed that hMSC administration in double-toxin-treated mice increased the expression of p-Akt and Bcl-2 and decreased Bax and cytochrome c expression. This study demonstrates that hMSC treatment protected against loss of neurons in the SN and the striatum induced by double toxin exposure, which may be mediated by modulation of inflammatory and cell survival and death signalingpathway as the hMSCs migrated from the peripheral circulation into the SN and striatum.

AB - Multiple system atrophy (MSA) is an adult-onset sporadic neurodegenerative disorder of unknown etiology featuring parkinsonism, ataxia, and autonomic failure in any combination. Because disease progression in MSA is rapid and no drug treatment consistently benefits MSA patients in the long term, neuroprotective or regenerative strategies may be invaluable in the management of MSA patients. In this study, we investigated whether human mesenchymal stem cells (hMSCs) had a protective effect on MSA using an animal model of double-toxin-induced MSA parkinsonism (MSA-P). MSA-P was established with coinjections of MPTP and 3-NP; hMSCs were injected into the tail vein 1 day after the last toxin injection. Three groups of mice were compared (i.e., control, MPTP + 3-NP, and MPTP + 3-NP with hMSC treatment) through histopathological, behavioral, and Western blot analyses. In the substantia nigra (SN) and the striatum, 2.0% and 3.8% of total injected hMSCs were observed, respectively. Compared with double-toxin-treated mice, hMSC treatment in double-toxin-treated mice significantly increased survival of TH-and NeuN-immunoreactive cells in the SN and the striatum, with coincident improvement in motor behavior. Additionally, hMSC treatment significantly decreased double-toxin-induced microglial and astroglial activation in the SN and striatum. Western blot analysis showed that hMSC administration in double-toxin-treated mice increased the expression of p-Akt and Bcl-2 and decreased Bax and cytochrome c expression. This study demonstrates that hMSC treatment protected against loss of neurons in the SN and the striatum induced by double toxin exposure, which may be mediated by modulation of inflammatory and cell survival and death signalingpathway as the hMSCs migrated from the peripheral circulation into the SN and striatum.

UR - http://www.scopus.com/inward/record.url?scp=80051780265&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80051780265&partnerID=8YFLogxK

U2 - 10.3727/096368910X540630

DO - 10.3727/096368910X540630

M3 - Article

VL - 20

SP - 827

EP - 835

JO - Cell Transplantation

JF - Cell Transplantation

SN - 0963-6897

IS - 6

ER -