Allogeneic mesenchymal stromal cells: Novel therapeutic option for mutated FLNA-associated respiratory failure in the pediatric setting

Gloria Pelizzo, Maria A. Avanzini, Elisa Lenta, Melissa Mantelli, Stefania Croce, Laura Catenacci, Gloria Acquafredda, Aurelio L. Ferraro, Caterina Giambanco, Lucia D'Amelio, Salvatore Giordano, Giuseppe Re, Floriana Zennaro, Valeria Calcaterra

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Mesenchymal stromal cell (MSC)-mediated therapeutic effects have been observed in the treatment of lung diseases. For the first time, this treatment was used as rescue therapy in a pediatric patient with a life-threatening respiratory syndrome associated with the filamin A (FLNA) gene mutation. Methods: A child with a new pathogenic variant of the FLNA gene c.7391_7403del (p.Val2464AlafsTer5), at the age of 18 months, due to serious and irreversible chronic respiratory failure, was treated with repeated intravenous infusions of allogeneic bone marrow (BM)-MSCs. The child's respiratory condition was monitored. Immunologic studies before each MSC treatment were performed. Results: No acute adverse events related to the MSC infusions were observed. After the second infusion, the child's respiratory condition progressively improved, with reduced necessity for mechanical ventilation support. A thorax computed tomography (CT) scan showed bilateral recovery of the basal parenchyma, anatomical-functional alignment and aerial penetration improvement. After the first MSC administration, an increase in Th17 and FoxP3+ T percentages in the peripheral blood was observed. After the second MSC infusion, a significant rise in the Treg/Th17 ratio was noted, as well as an increased percentage of CD20+/CD19+ B lymphocytes and augmented PHA-induced proliferation. Discussion: MSC infusions are a promising therapeutic modality for patients in respiratory failure, as observed in this pediatric patient with an FLNA mutation. MSCs may have an immunomodulatory effect and thus mitigate lung injury; although in this case, MSC antimicrobial effects may have synergistically impacted the clinical improvements. Further investigations are planned to establish the safety and efficacy of this treatment option for interstitial lung diseases in children.

Original languageEnglish
JournalPediatric Pulmonology
DOIs
Publication statusAccepted/In press - Jan 1 2019

Fingerprint

Filamins
Mesenchymal Stromal Cells
Respiratory Insufficiency
Pediatrics
Therapeutics
Mutation
Interstitial Lung Diseases
Lung Injury
Therapeutic Uses
Artificial Respiration
Intravenous Infusions
Lung Diseases
Genes
B-Lymphocytes
Thorax
Bone Marrow
Tomography
Safety

Keywords

  • allogeneic
  • children
  • filamin A mutation
  • interstitial lung disease
  • mesenchymal stromal cell

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pulmonary and Respiratory Medicine

Cite this

Allogeneic mesenchymal stromal cells : Novel therapeutic option for mutated FLNA-associated respiratory failure in the pediatric setting. / Pelizzo, Gloria; Avanzini, Maria A.; Lenta, Elisa; Mantelli, Melissa; Croce, Stefania; Catenacci, Laura; Acquafredda, Gloria; Ferraro, Aurelio L.; Giambanco, Caterina; D'Amelio, Lucia; Giordano, Salvatore; Re, Giuseppe; Zennaro, Floriana; Calcaterra, Valeria.

In: Pediatric Pulmonology, 01.01.2019.

Research output: Contribution to journalArticle

Pelizzo, Gloria ; Avanzini, Maria A. ; Lenta, Elisa ; Mantelli, Melissa ; Croce, Stefania ; Catenacci, Laura ; Acquafredda, Gloria ; Ferraro, Aurelio L. ; Giambanco, Caterina ; D'Amelio, Lucia ; Giordano, Salvatore ; Re, Giuseppe ; Zennaro, Floriana ; Calcaterra, Valeria. / Allogeneic mesenchymal stromal cells : Novel therapeutic option for mutated FLNA-associated respiratory failure in the pediatric setting. In: Pediatric Pulmonology. 2019.
@article{c1830f9690594ac2b431538995f0a8e7,
title = "Allogeneic mesenchymal stromal cells: Novel therapeutic option for mutated FLNA-associated respiratory failure in the pediatric setting",
abstract = "Background: Mesenchymal stromal cell (MSC)-mediated therapeutic effects have been observed in the treatment of lung diseases. For the first time, this treatment was used as rescue therapy in a pediatric patient with a life-threatening respiratory syndrome associated with the filamin A (FLNA) gene mutation. Methods: A child with a new pathogenic variant of the FLNA gene c.7391_7403del (p.Val2464AlafsTer5), at the age of 18 months, due to serious and irreversible chronic respiratory failure, was treated with repeated intravenous infusions of allogeneic bone marrow (BM)-MSCs. The child's respiratory condition was monitored. Immunologic studies before each MSC treatment were performed. Results: No acute adverse events related to the MSC infusions were observed. After the second infusion, the child's respiratory condition progressively improved, with reduced necessity for mechanical ventilation support. A thorax computed tomography (CT) scan showed bilateral recovery of the basal parenchyma, anatomical-functional alignment and aerial penetration improvement. After the first MSC administration, an increase in Th17 and FoxP3+ T percentages in the peripheral blood was observed. After the second MSC infusion, a significant rise in the Treg/Th17 ratio was noted, as well as an increased percentage of CD20+/CD19+ B lymphocytes and augmented PHA-induced proliferation. Discussion: MSC infusions are a promising therapeutic modality for patients in respiratory failure, as observed in this pediatric patient with an FLNA mutation. MSCs may have an immunomodulatory effect and thus mitigate lung injury; although in this case, MSC antimicrobial effects may have synergistically impacted the clinical improvements. Further investigations are planned to establish the safety and efficacy of this treatment option for interstitial lung diseases in children.",
keywords = "allogeneic, children, filamin A mutation, interstitial lung disease, mesenchymal stromal cell",
author = "Gloria Pelizzo and Avanzini, {Maria A.} and Elisa Lenta and Melissa Mantelli and Stefania Croce and Laura Catenacci and Gloria Acquafredda and Ferraro, {Aurelio L.} and Caterina Giambanco and Lucia D'Amelio and Salvatore Giordano and Giuseppe Re and Floriana Zennaro and Valeria Calcaterra",
year = "2019",
month = "1",
day = "1",
doi = "10.1002/ppul.24497",
language = "English",
journal = "Pediatric Pulmonology",
issn = "8755-6863",
publisher = "Wiley-Liss Inc.",

}

TY - JOUR

T1 - Allogeneic mesenchymal stromal cells

T2 - Novel therapeutic option for mutated FLNA-associated respiratory failure in the pediatric setting

AU - Pelizzo, Gloria

AU - Avanzini, Maria A.

AU - Lenta, Elisa

AU - Mantelli, Melissa

AU - Croce, Stefania

AU - Catenacci, Laura

AU - Acquafredda, Gloria

AU - Ferraro, Aurelio L.

AU - Giambanco, Caterina

AU - D'Amelio, Lucia

AU - Giordano, Salvatore

AU - Re, Giuseppe

AU - Zennaro, Floriana

AU - Calcaterra, Valeria

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Mesenchymal stromal cell (MSC)-mediated therapeutic effects have been observed in the treatment of lung diseases. For the first time, this treatment was used as rescue therapy in a pediatric patient with a life-threatening respiratory syndrome associated with the filamin A (FLNA) gene mutation. Methods: A child with a new pathogenic variant of the FLNA gene c.7391_7403del (p.Val2464AlafsTer5), at the age of 18 months, due to serious and irreversible chronic respiratory failure, was treated with repeated intravenous infusions of allogeneic bone marrow (BM)-MSCs. The child's respiratory condition was monitored. Immunologic studies before each MSC treatment were performed. Results: No acute adverse events related to the MSC infusions were observed. After the second infusion, the child's respiratory condition progressively improved, with reduced necessity for mechanical ventilation support. A thorax computed tomography (CT) scan showed bilateral recovery of the basal parenchyma, anatomical-functional alignment and aerial penetration improvement. After the first MSC administration, an increase in Th17 and FoxP3+ T percentages in the peripheral blood was observed. After the second MSC infusion, a significant rise in the Treg/Th17 ratio was noted, as well as an increased percentage of CD20+/CD19+ B lymphocytes and augmented PHA-induced proliferation. Discussion: MSC infusions are a promising therapeutic modality for patients in respiratory failure, as observed in this pediatric patient with an FLNA mutation. MSCs may have an immunomodulatory effect and thus mitigate lung injury; although in this case, MSC antimicrobial effects may have synergistically impacted the clinical improvements. Further investigations are planned to establish the safety and efficacy of this treatment option for interstitial lung diseases in children.

AB - Background: Mesenchymal stromal cell (MSC)-mediated therapeutic effects have been observed in the treatment of lung diseases. For the first time, this treatment was used as rescue therapy in a pediatric patient with a life-threatening respiratory syndrome associated with the filamin A (FLNA) gene mutation. Methods: A child with a new pathogenic variant of the FLNA gene c.7391_7403del (p.Val2464AlafsTer5), at the age of 18 months, due to serious and irreversible chronic respiratory failure, was treated with repeated intravenous infusions of allogeneic bone marrow (BM)-MSCs. The child's respiratory condition was monitored. Immunologic studies before each MSC treatment were performed. Results: No acute adverse events related to the MSC infusions were observed. After the second infusion, the child's respiratory condition progressively improved, with reduced necessity for mechanical ventilation support. A thorax computed tomography (CT) scan showed bilateral recovery of the basal parenchyma, anatomical-functional alignment and aerial penetration improvement. After the first MSC administration, an increase in Th17 and FoxP3+ T percentages in the peripheral blood was observed. After the second MSC infusion, a significant rise in the Treg/Th17 ratio was noted, as well as an increased percentage of CD20+/CD19+ B lymphocytes and augmented PHA-induced proliferation. Discussion: MSC infusions are a promising therapeutic modality for patients in respiratory failure, as observed in this pediatric patient with an FLNA mutation. MSCs may have an immunomodulatory effect and thus mitigate lung injury; although in this case, MSC antimicrobial effects may have synergistically impacted the clinical improvements. Further investigations are planned to establish the safety and efficacy of this treatment option for interstitial lung diseases in children.

KW - allogeneic

KW - children

KW - filamin A mutation

KW - interstitial lung disease

KW - mesenchymal stromal cell

UR - http://www.scopus.com/inward/record.url?scp=85071939808&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85071939808&partnerID=8YFLogxK

U2 - 10.1002/ppul.24497

DO - 10.1002/ppul.24497

M3 - Article

C2 - 31468740

AN - SCOPUS:85071939808

JO - Pediatric Pulmonology

JF - Pediatric Pulmonology

SN - 8755-6863

ER -