Amniotic fluid stem cells with low γ-interferon response showed behavioral improvement in Parkinsonism rat model

PLoS One. 2013 Sep 30;8(9):e76118. doi: 10.1371/journal.pone.0076118. eCollection 2013.

Abstract

Amniotic fluid stem cells (AFSCs) are multipotent stem cells that may be used in transplantation medicine. In this study, AFSCs established from amniocentesis were characterized on the basis of surface marker expression and differentiation potential. To further investigate the properties of AFSCs for translational applications, we examined the cell surface expression of human leukocyte antigens (HLA) of these cells and estimated the therapeutic effect of AFSCs in parkinsonian rats. The expression profiles of HLA-II and transcription factors were compared between AFSCs and bone marrow-derived mesenchymal stem cells (BMMSCs) following treatment with γ-IFN. We found that stimulation of AFSCs with γ-IFN prompted only a slight increase in the expression of HLA-Ia and HLA-E, and the rare HLA-II expression could also be observed in most AFSCs samples. Consequently, the expression of CIITA and RFX5 was weakly induced by γ-IFN stimulation of AFSCs compared to that of BMMSCs. In the transplantation test, Sprague Dawley rats with 6-hydroxydopamine lesioning of the substantia nigra were used as a parkinsonian-animal model. Following the negative γ-IFN response AFSCs injection, apomorphine-induced rotation was reduced by 75% in AFSCs engrafted parkinsonian rats but was increased by 53% in the control group after 12-weeks post-transplantation. The implanted AFSCs were viable, and were able to migrate into the brain's circuitry and express specific proteins of dopamine neurons, such as tyrosine hydroxylase and dopamine transporter. In conclusion, the relative insensitivity AFSCs to γ-IFN implies that AFSCs might have immune-tolerance in γ-IFN inflammatory conditions. Furthermore, the effective improvement of AFSCs transplantation for apomorphine-induced rotation paves the way for the clinical application in parkinsonian therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amniotic Fluid / cytology*
  • Animals
  • Benzothiazoles
  • DNA Primers / genetics
  • Diamines
  • Fluorescent Antibody Technique
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics*
  • HLA Antigens / metabolism*
  • Humans
  • Immunohistochemistry
  • Interferon-gamma / pharmacology
  • Mesenchymal Stem Cells / metabolism
  • Multipotent Stem Cells / immunology
  • Multipotent Stem Cells / metabolism*
  • Organic Chemicals
  • Oxidopamine / adverse effects
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / immunology
  • Parkinsonian Disorders / therapy*
  • Polymerase Chain Reaction
  • Quinolines
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cell Transplantation / methods*
  • Substantia Nigra / drug effects
  • Substantia Nigra / pathology
  • Transcription Factors / metabolism

Substances

  • Benzothiazoles
  • DNA Primers
  • Diamines
  • HLA Antigens
  • Organic Chemicals
  • Quinolines
  • Transcription Factors
  • SYBR Green I
  • Interferon-gamma
  • Oxidopamine

Grants and funding

This work was supported by Grant 101-EC-17-A-01-04-0525 from the Ministry of Economic Affairs, Taiwan (http://www.moea.gov.tw), and Grant NSC 99-2311-B-080-001-MY2 and NSC97-2314-B-281-002-MY3 from the National Science Council, Taiwan (http://www.sinica.edu.tw). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.