Treatment of silicosis with hepatocyte growth factor-modified autologous bone marrow stromal cells: a non-randomized study with follow-up

Abstract

ABSTRACT. Pulmonary silicosis is an irreversible and untreatable disease that is characterized by interstitial lesions and perpetual fibrosis in the lungs. This study was performed to determine whether mesenchymal stem cells (MSCs) and hepatocyte growth factor (HGF) could exhibit therapeutic effects on human silicosis. This nonrandomized uncontrolled trial comprised four patients with pulmonary silicosis who had developed lung fibrosis and received autologous bone marrow MSCs previously transfected by a vector containing human HGF cDNA (MSCs/HGF). MSCs/HGF were intravenously administered weekly for three consecutive weeks at a dose of 2 x 10 6 cells/kg. Pulmonary function, high kilo-voltage chest X-ray radiography, computed tomography (CT) scan, and peripheral blood lymphocyte subset and serum IgG concentrations were evaluated after cell therapy. The treatment was found to be generally safe. Symptoms such as cough and chest distress gradually ameliorated at six months post-therapy, accompanied by the significant improvement of pulmonary function. The ratios of the peripheral CD4-and CD8-positive cell concentrations were increased (P < 0.05). Furthermore, the serum IgG levels in these patients were decreased and reached the normal range (P < 0.05). CT scans showed partial absorption of the nodular and reticulonodular lesions in the lungs during follow-up of at least 12 months. The effectiveness of this novel regimen observed in these patients suggests that a placebo-controlled clinical trial needs to be developed. This study carries trial registration No. NCT01977131 (ClinicalTrials.gov).

Serious adverse events of cell therapy for respiratory diseases: a systematic review and meta-analysis

“…The marked data were used in meta-analysis. For case series [12, 15–17, 20, 21, 23, 27, 31], we combined individual data using the formulas, $\stackrel{true¯}{X}=\frac{\sum x}{n}$ and $\text{italicSD}=\sqrt{\frac{\sum {\left(x-\overline{x}\right)}^2}{n-1}}$, where $x$ stands for variance, $\overline{X}$ is the mean of pooled individual data, and $n$ is the sample size. To combine data of subgroups, mean and SD were computed with these equations: $\text{italicmean}=\frac{{\text{N}}_1{\text{M}}_1+{\text{N}}_2{\text{M}}_2}{{\text{N}}_1+{\text{N}}_2}$ and $SD=\sqrt{\frac{\left({\text{N}}_1-1\right){\text{SD}}_1^2+\left({\text{N}}_2-1\right){\text{SD}}_2^2+\frac{{\text{N}}_1{\text{N}}_2}{{\text{N}}_1+{\text{N}}_2}\left({\text{M}}_1^2+{\text{M}}_2^2-2{\text{M}}_1{\text{M}}_2\right)}{{\text{N}}_1+{\text{N}}_2-1}}$, where N and M represent the size and mean of subgroup, respectively.…”

Evaluation of serum HGF and CK18 levels in patients with esophageal cancer

“…It has been suggested that the HGF/c-Met signaling pathway is associated with malignant cancers, and may be involved with cancer metastasis (Anderson et al, 2006). Conversely, recent studies have shown that HGF may exhibit therapeutic effects on some diseases such as human silicosis (Liu et al, 2015) and myocardial ischemic injury (Wang et al, 2014). The possible role of HGF and CK18 in the development and progression of ESCC remains unclear.…”

Silica‐associated lung disease: An old‐world exposure in modern industries

“…Other antifibrotic agents including tadalafil are also being trialled in animal models. 90 Cell-based therapy including bone marrow-derived mononuclear cell 91 and mesenchymal cell transplantation 92 have both demonstrated some benefit in animal models and are currently undergoing trials in humans. 93…”