Therapeutic effects of bone marrow-derived mononuclear cells from healthy or silicotic donors on recipient silicosis mice

Helena D'Anunciação de Oliveira; Elga Bernardo Bandeira de Melo; Johnatas Dutra Silva; Jamil Zola Kitoko; Bianca Gutfilen; Thiago Barboza; Sergio Augusto Lopes de Souza; Christina Maeda Takiya; Patricia Rieken Macedo Rocco; Miquéias Lopes-Pacheco; Marcelo Marcos Morales

doi:10.1186/s13287-017-0699-7

Therapeutic effects of bone marrow-derived mononuclear cells from healthy or silicotic donors on recipient silicosis mice

Stem Cell Res Ther. 2017 Nov 10;8(1):259. doi: 10.1186/s13287-017-0699-7.

Affiliations

¹ Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
² Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
³ Department of Radiology, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
⁴ Laboratory of Cellular Pathology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
⁵ Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. mmorales@biof.ufrj.br.

Abstract

Background: Administration of bone marrow mononuclear cells (BMMCs) modulates lung inflammation and fibrosis in experimental silicosis. However, no studies have evaluated whether silicosis affects the efficacy of autologous BMMCs treatment. We hypothesized that BMMCs obtained from healthy or silicotic mice may improve lung function, but they might affect the inflammatory and fibrotic processes differently in experimental silicosis.

Methods: C57BL/6 mice were randomly divided into control (C) and silicosis (SIL) groups. Mice in the SIL group were instilled with silica particles intratracheally; the C animals received saline using the same protocol. On day 15, the animals were treated with saline (Sal) or BMMCs (2 × 10⁶ cells) from healthy (BMMC-healthy) and silicotic (BMMC-sil) donors. Lung mechanics were measured, and lungs were collected for histology and molecular biology analysis.

Results: BMMCs obtained from healthy and silicotic donors presented similar percentages of cell populations. ^99mTc-BMMCs tracking revealed preferential migration of cells to the liver, and only a few GFP⁺ BMMCs were observed in lung tissue 24 h after treatment, regardless of donor type. Both the SIL-BMMC-healthy and SIL-BMMC-sil groups showed improvement in lung function, a reduction in the fractional area of granuloma, and a decrease in the number of mononuclear and apoptotic cells in lung parenchyma. In addition, the number of F4/80⁺ macrophages, the levels of interleukin-1 beta and transforming growth factor beta, and collagen fiber content in granuloma were reduced in SIL-BMMC-healthy mice, whereas mRNA expression of MMP-9 and procollagen I and III was reduced in the SIL-BMMC-sil group.

Conclusions: Administration of BMMCs from healthy and silicotic donors reduced lung inflammation and fibrosis, thus improving lung function. In addition, BMMC-healthy exhibited a greater improvement in lung morpho-functional changes in murine model of silicosis.

Keywords: Bone marrow mononuclear cells; Cell therapy; Inflammation; Lung fibrosis; Silicosis.

MeSH terms

Animals
Bone Marrow
Cell- and Tissue-Based Therapy / methods*
Female
Leukocytes, Mononuclear
Male
Mice
Mice, Inbred C57BL
Silicosis