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



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.


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.


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.


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.


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



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.


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.


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.


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.


Autoimmunerkrankungen Systemischer Lupus erythematosus Cyclophosphamid Autoantikörper Lupusnephritis 



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.


  1. 1.
    Kalloo S, Aggarwal N, Mohan P et al (2013) Lupus nephritis: treatment of resistant disease. Clin J Am Soc Nephrol 8:154–161CrossRefGoogle Scholar
  2. 2.
    Alunno A, Bartoloni E, Bistoni O et al (2012) Balance between regulatory T and Th17 cells in systemic lupus erythematosus: the old and the new. Clin Dev Immunol 2012:823085CrossRefGoogle Scholar
  3. 3.
    Park MJ, Kwok SK, Lee SH et al (2015) Adipose tissue-derived mesenchymal stem cells induce expansion of interleukin-10-producing regulatory B cells and ameliorate autoimmunity in a murine model of systemic lupus erythematosus. Cell Transplant 24:2367–2377CrossRefGoogle Scholar
  4. 4.
    Ribeiro A, Laranjeira P, Mendes S et al (2013) Mesenchymal stem cells from umbilical cord matrix, adipose tissue and bone marrow exhibit different capability to suppress peripheral blood B, natural killer and T cells. Stem Cell Res Ther 15:125–141CrossRefGoogle Scholar
  5. 5.
    Nie X, Deng R, Xiang L et al (2016) Reno-protective effect and mechanism study of Huang Lian Jie Du Decoction on lupus nephritis MRL/lpr mice. BMC Complement Altern Med 16:448–459CrossRefGoogle Scholar
  6. 6.
    Schäfer R, Daikeler T (2016) Mesenchymal stem/stroma cells: therapeutic potential in the treatment of autoimmune diseases. Z Rheumatol 75:786–794CrossRefGoogle Scholar
  7. 7.
    Lin CS, Lin G, Lue TF (2012) Allogeneic and xenogeneic transplantation of adipose-derived stem cells in immunocompetent recipients without immunosuppressants. Stem Cells Dev 21:2770–2778CrossRefGoogle Scholar
  8. 8.
    EI-Badawy A, Amer M, Abdelbaset R et al (2016) Adipose stem cells display higher regenerative capacities and more adaptable electro-kinetic properties compared to bone marrow-derived mesenchymal stromal cells. Sci Rep 6:37801CrossRefGoogle Scholar
  9. 9.
    Szmyrka-Kaczmarek M, Kosmaczewska A, Ciszak L et al (2014) Peripheral blood Th17/Treg imbalance in patients with low-active systemic lupus erythematosus. Postepy Hig Med Dosw 68:893–898CrossRefGoogle Scholar
  10. 10.
    Handono K, Pratama MZ, Endharti AT et al (2015) Treatment of low doses curcumin could modulate Th17/Treg balance specifically on CD4+T cell cultures of systemic lupus erythematosus patients. Cent Eur J Immunol 40:461–469CrossRefGoogle Scholar
  11. 11.
    Sohni A, Verfaillie CM (2013) Mesenchymal stem cells migration homing and tracking. Stem Cells Int 2013:130763CrossRefGoogle Scholar

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

Personalised recommendations