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Zeitschrift für Rheumatologie

, Volume 78, Issue 1, pp 82–88 | Cite as

Transplantation of adipose tissue-derived stem cells ameliorates autoimmune pathogenesis in MRL/lpr mice

Modulation of the balance between Th17 and Treg
  • W. Zhang
  • Y.-L. Feng
  • C.-Y. Pang
  • F.-A. Lu
  • Y.-F. WangEmail author
Originalien
  • 134 Downloads

Abstract

Background

Mesenchymal stem cells (MSCs) are multipotent cells characterized by immunomodulatory properties and are therefore considered a promising tool for the treatment of autoimmune diseases. In this study, we aimed to investigate whether transplantation of adipose tissue-derived stem cells (ADSCs) affects the autoimmune pathogenesis in MRL/lpr mice.

Methods

Fifteen 12-week-old MRL/lpr mice were randomly divided into three groups: ADSC, cyclophosphamide (CTX), and control groups, with five mice in each group. ADSC and control groups were injected with 1 × 106 ADSCs or PBS, respectively, via the tail vein, once a week for 8 weeks. The CTX group was injected with CTX at a dose of 15 mg/kg body weight, once a week for 2 weeks, and this was repeated after 2 weeks rest. Proteinuria, anti-double-stranded DNA (anti-dsDNA) antibody, and serum creatinine levels were then measured. The populations of Th17 and Treg cells in the spleen were detected by flow cytometry. All statistical analyses were performed using least square difference.

Results

Eight weeks after treatment, the 24 h proteinuria, anti-dsDNA antibody levels, and serum creatinine were decreased significantly with transplantation of mouse ADSCs. ADSCs markedly reduced the number of TH17 cells, increased Treg cells, and improved renal pathology.

Conclusion

Our results indicate that transplantation of ADSCs could significantly inhibit autoimmune progression in MRL/lpr mice and the efficacy of ADSCs was comparable to that of CTX.

Keywords

Autoimmune diseases Systemic lupus erythematosus Cyclophosphamide Autoantibodies Lupus nephritis 

Transplantation von Fettgewebsstammzellen auf die Autoimmunpathogenese bei MRL/lpr-Mäusen

Modulation des Gleichgewichts zwischen TH17- und Treg-Zellen

Zusammenfassung

Hintergrund

Mesenchymale Stammzellen (MSC) sind multipotente Zellen, die sich durch immunmodulatorische Eigenschaften auszeichnen und daher als vielversprechendes Instrument zur Behandlung von Autoimmunkrankheiten gelten. In der vorliegenden Studie war es das Ziel zu untersuchen, ob die Transplantation von Fettgewebsstammzellen („adipose tissue-derived stem cells“, ADSC) die Autoimmunpathogenese bei MRL/lpr-Mäusen beeinflusst.

Methoden

Im Alter von 12 Wochen wurden 15 MRL/lpr-Mäuse randomisiert in 3 Gruppen eingeteilt: ADSC, Cyclophosphamid (CTX) und Kontrollen, jede Gruppe enthielt 5 Mäuse. Die ADSC- und die Kontrollgruppe erhielten jeweils einmal wöchentlich über 8 Wochen eine Injektion von 1 × 106 ADSC bzw. Phosphatpuffer (PBS) über die Schwanzvene. Der CTX-Gruppe wurde CTX in einer Dosis von 15 mg/kg KG einmal pro Woche über 2 Wochen injiziert, dies wurde nach 2 Wochen Pause wiederholt. Danach wurden Proteinurie, Anti-dsDNA-Antikörper und Serumkreatininwerte gemessen. Mittels Durchflusszytometrie wurden die Populationen von TH17- und Treg-Zellen in der Milz ermittelt. Alle statistischen Analysen wurden unter Verwendung der Differenz der kleinsten Quadrate („least square difference“) durchgeführt.

Ergebnisse

Mit Transplantation der Maus-ADSC nahmen 8 Wochen nach der Behandlung die 24-h-Proteinurie, und die Werte für Anti-dsDNA-Antikörper sowie Serumkreatinin signifikant ab. In der ADSC-Gruppe nahm die Anzahl der TH17-Zellen deutlich ab, es stieg die Anzahl der Treg-Zellen, und die pathologischen Veränderungen der Nieren besserten sich.

Schlussfolgerung

Den vorliegenden Ergebnissen zufolge könnte die Transplantation von ADSC das Fortschreiten autoimmuner Veränderungen bei MRL/lpr-Mäusen signifikant hemmen, dabei war die Wirksamkeit von ADSC mit der von CTX vergleichbar.

Schlüsselwörter

Autoimmunerkrankungen Systemischer Lupus erythematosus Cyclophosphamid Autoantikörper Lupusnephritis 

Notes

Funding

This work was supported by the National Nature Science Foundation of China (No. 81360464), the key fundamental research Project of Inner Mongolia and the College Scientific Research Project of Inner Mongolia (No. NJZC212).

Compliance with ethical guidelines

Conflict of interest

W. Zhang, Y.-L. Feng, C.-Y. Pang, F.-A. Lu, and Y.-F. Wang declare that they have no competing interests.

The study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Baotou Medical College. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2018

Authors and Affiliations

  • W. Zhang
    • 1
    • 2
  • Y.-L. Feng
    • 3
  • C.-Y. Pang
    • 1
    • 2
  • F.-A. Lu
    • 1
    • 2
  • Y.-F. Wang
    • 1
    • 2
    Email author
  1. 1.Department of Rheumatology and ImmunologyFirst Hospital Affiliated to Baotou Medical College (Institution of Rheumatology and Immunology of BaoTou medical college)BaotouChina
  2. 2.Inner Mongolia key laboratory of autoimmunityBaotouChina
  3. 3.Department of Ophthalmolo gyFirst Hospital Affiliated to Baotou Medical CollegeBaotouChina

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