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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)322-334
JournalCytotherapy
Volume20
Issue number3
DOIs
Publication statusPublished - 2018

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Mesenchymal Stromal Cells
Pediatrics
Congenital Nephrosis
Adrenal Cortex Hormones
Bone Marrow
Therapeutics
Podocytes
Immunosuppressive Agents
Coculture Techniques
Plasma Cells
Immunosuppression
Cell Differentiation
Immune System
B-Lymphocytes
Theoretical Models
Steroids
Cell Proliferation
Tissue Donors
Morbidity
Kidney

Keywords

  • Bone marrow niche
  • Idiopathic nephrotic syndrome
  • Immunomodulatory properties
  • Mesenchymal stromal cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Genetics(clinical)
  • Cell Biology
  • Transplantation
  • Cancer Research

Cite this

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title = "Phenotypic and functional characterization of mesenchymal stromal cells isolated from pediatric patients with severe idiopathic nephrotic syndrome",
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",
author = "Nadia Starc and Min Li and Mattia Algeri and Antonella Conforti and Luigi Tomao and Angela Pitisci and Francesco Emma and Giovanni Montini and Piergiorgio Messa and Franco Locatelli and Bernardo, {Maria Ester} and Marina Vivarelli",
year = "2018",
doi = "10.1016/j.jcyt.2017.12.001",
language = "English",
volume = "20",
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journal = "Cytotherapy",
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TY - JOUR

T1 - Phenotypic and functional characterization of mesenchymal stromal cells isolated from pediatric patients with severe idiopathic nephrotic syndrome

AU - Starc, Nadia

AU - Li, Min

AU - Algeri, Mattia

AU - Conforti, Antonella

AU - Tomao, Luigi

AU - Pitisci, Angela

AU - Emma, Francesco

AU - Montini, Giovanni

AU - Messa, Piergiorgio

AU - Locatelli, Franco

AU - Bernardo, Maria Ester

AU - Vivarelli, Marina

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Bone marrow niche

KW - Idiopathic nephrotic syndrome

KW - Immunomodulatory properties

KW - Mesenchymal stromal cells

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JO - Cytotherapy

JF - Cytotherapy

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