Elevated Numbers of Circulating Very Small Embryonic-Like Stem Cells (VSELs) and Intermediate CD14++CD16+ Monocytes in IgA Nephropathy

Stem Cell Rev Rep. 2018 Oct;14(5):686-693. doi: 10.1007/s12015-018-9840-y.


IgA nephropathy (IgAN) is recognized as most frequent form of primary glomerulonephritis worldwide. IgAN is associated with renal degradation occurring due to irreversible pathological changes leading to glomerulosclerosis and interstitial fibrosis. It remains poorly understood whether and to what extent these changes are followed by the activation of regenerative mechanisms. Therefore, in this study we aimed to evaluate regenerative potential of IgAN patients by quantitating the frequencies of several stem cell types, namely circulating very small embryonic-like stem cells (VSELs), hematopoietic stem cells (HSCs), endothelial progenitor cells (EPCs) as well as different monocyte subsets with varying maturation and angiopoietic potential. Moreover, we analyzed whether changes in stem cell and monocyte frequencies were related to alterations of several chemotactic factors (stromal derived-factor (SDF-1), angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2)) and a marker of monocyte/macrophage activation, namely soluble form of CD163 receptor (sCD163). We showed that IgAN patients presented with enhanced levels of VSELs, but not other stem cell types. We also demonstrated significantly elevated numbers of intermediate monocytes known for their M2-like properties as well as high angiopoietic potential and CD163 expression. This finding was accompanied by detection of elevated sCD163 plasma levels in IgAN patients. Taking together, we demonstrated here that IgAN is associated with selective mobilization of VSELs and increased maturation of monocytes towards M2-like and angiopoietic phenotype. These findings contribute to better understanding of the role of regenerative mechanisms in the pathogenesis of chronic inflammation in the course of IgAN.

Keywords: Ang-1; Ang-2; EPCs; HSCs; IgA nephropathy; Monocytes; Regeneration; SDF-1; VSELs; sCD163.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antigens, CD / blood
  • Antigens, Differentiation, Myelomonocytic / blood
  • Chemokine CXCL12 / metabolism
  • Embryonic Stem Cells / metabolism
  • Embryonic Stem Cells / pathology*
  • Endothelial Progenitor Cells / metabolism
  • Endothelial Progenitor Cells / pathology*
  • Glomerulonephritis / blood*
  • Glomerulonephritis / pathology
  • Glomerulonephritis, IGA / blood*
  • Glomerulonephritis, IGA / pathology
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / pathology
  • Humans
  • Immunoglobulin A / blood
  • Lipopolysaccharide Receptors / metabolism
  • Peripheral Blood Stem Cells / cytology
  • Receptors, Cell Surface / blood
  • Receptors, IgG / metabolism


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Immunoglobulin A
  • Lipopolysaccharide Receptors
  • Receptors, Cell Surface
  • Receptors, IgG