Phenotypic and functional characterization of mesenchymal stromal cells isolated from pediatric patients with severe idiopathic nephrotic syndrome

Cytotherapy. 2018 Mar;20(3):322-334. doi: 10.1016/j.jcyt.2017.12.001. Epub 2017 Dec 29.

Abstract

Background: Idiopathic nephrotic syndrome (INS) is one of the most common renal diseases in the pediatric population; considering the role of the immune system in its pathogenesis, corticosteroids are used as first-line immunosuppressive treatment. Due to its chronic nature and tendency to relapse, a significant proportion of children experience co-morbidity due to prolonged exposure to corticosteroids and concomitant immunosuppression with second-line, steroid-sparing agents. Mesenchymal stromal cells (MSCs) are multipotent cells that represent a key component of the bone marrow (BM) microenvironment; given their unique immunoregulatory properties, their clinical use may be exploited as an alternative therapeutic approach in INS treatment.

Methods: In view of the possibility of exploiting their immunoregulatory properties, we performed a phenotypical and functional characterization of MSCs isolated from BM of five INS patients (INS-MSCs; median age, 13 years; range, 11-16 years) in comparison with MSCs isolated from eight healthy donors (HD-MSCs). MSCs were expanded ex vivo and then analyzed for their properties.

Results: Morphology, proliferative capacity, immunophenotype and differentiation potential did not differ between INS-MSCs and HD-MSCs. In an allogeneic setting, INS-MSCs were able to prevent both T- and B-cell proliferation and plasma-cell differentiation. In an in-vitro model of experimental damage to podocytes, co-culture with INS-MSCs appeared to be protective.

Discussion: Our results demonstrate that INS-MSCs maintain the main biological and functional properties typical of HD-MSCs; these data suggest that MSCs may be used in autologous cellular therapy approaches for INS treatment.

Keywords: bone marrow niche; idiopathic nephrotic syndrome; immunomodulatory properties; mesenchymal stromal cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Bone Marrow / immunology
  • Cell Differentiation
  • Cell Proliferation
  • Child
  • Coculture Techniques
  • Female
  • Humans
  • Immunophenotyping
  • Lymphocyte Activation
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / physiology*
  • Nephrotic Syndrome / pathology*
  • Pilot Projects
  • Podocytes / cytology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / physiology

Supplementary concepts

  • Nephrosis, congenital