Adipose-derived stem cells improve renal function in a mouse model of IgA nephropathy

Young Youl Hyun, In Ok Kim, Mi Hyung Kim, Deok Hwa Nam, Mi Hwa Lee, Jung Eun Kim, Hye Kyoung Song, Jin Joo Cha, Young Sun Kang, Ji Eun Lee, Hyun Wook Kim, Jee Young Han, Dae Ryong Cha

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5 Citations (Scopus)

Abstract

T-cell dysregulation plays an important role in the pathogenesis of immunoglobulin A nephropathy (IgAN). Adipose-derived stem cells (ASCs) have been reported to be able to prevent tissue damage through immunemodulating effects. To evaluate the effects of ASCs in high IgA ddY (HIGA) mice, ASCs were isolated from HIGA mice with different stages of IgAN before and after disease onset. ASCs were injected at a dose of 5 × 106 cells/kg body weight through the tail vein every 2 weeks for 3 months. Although the administered ASCs were rarely detected in the glomeruli, 24-h proteinuria was markedly decreased in all ASC-treated groups. Although glomerular deposition of IgA was not significantly different among groups, mesangial proliferation and glomerulosclerosis were dramatically decreased in most ASC treatment groups. In addition, levels of fibrotic and inflammatory molecules were markedly decreased by ASC treatment. Interestingly, ASC therapy significantly decreased Th1 cytokine activity in the kidney and caused a shift to Th2 responses in spleen T-cells as determined by FACS analysis. Furthermore, conditioned media from ASCs abrogated aggregated IgA-induced Th1 cytokine production in cultured HIGA mesangial cells. These results suggest that the beneficial effects of ASC treatment in IgAN occur via paracrine mechanisms that modulate the Th1/Th2 cytokine balance. ASCs are therefore a promising new therapeutic agent for the treatment of IgAN.

Original languageEnglish
Pages (from-to)2425-2439
Number of pages15
JournalCell Transplantation
Volume21
Issue number11
DOIs
Publication statusPublished - 2012

Keywords

  • Adipose-derived stem cells (ASCs)
  • Glomerulosclerosis
  • HIGA mice
  • Proteinuria
  • Th1 cytokine

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

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  • Cite this

    Hyun, Y. Y., Kim, I. O., Kim, M. H., Nam, D. H., Lee, M. H., Kim, J. E., Song, H. K., Cha, J. J., Kang, Y. S., Lee, J. E., Kim, H. W., Han, J. Y., & Cha, D. R. (2012). Adipose-derived stem cells improve renal function in a mouse model of IgA nephropathy. Cell Transplantation, 21(11), 2425-2439. https://doi.org/10.3727/096368912X639008