The effect of adipose stem cell therapy on pulmonary fibrosis induced by repetitive intratracheal bleomycin in mice

Abstract

Adipose stem cells (ASCs) are detectable in the parenchyma and large airways of lungs after systemic administration, and ameliorate inflammatory infiltration and cell death in animal models of emphysema. We evaluated whether ASC treatment could attenuate lung fibrosis induced by repetitive intratracheal bleomycin administration. Male 8-week-old C57BL/6J mice (control group, bleomycin-only group, and bleomycin-plus-ASC group) were used. Eight biweekly doses of bleomycin were injected intratracheally via an intubation procedure at a dose of 0.04 units in a total volume of 100 μL of sterile saline. During the latter 2 months of the 4-month bleomycin exposure, human ASCs (3 × 10(5) cells) were administered repeatedly via intraperitoneal injection at the same time as bleomycin. Lung tissues were evaluated for histology, collagen content, TUNEL staining, and TGF-β levels. Bronchoalveolar lavage (BAL) was performed for cell counting. Administrations of ASCs ameliorated the deleterious effects of repetitive intratracheal instillation of bleomycin, namely hyperplasia of Club cells (Clara cells) and cuboidal alveolar epithelial cells, infiltration of the perialveolar ducts by inflammatory cells, septal thickening, enlarged alveoli, and extensive fibrosis. Addition of ASC led to suppression of bleomycin-induced epithelial cell apoptosis and expression of TGF-β. These results suggest a useful therapeutic effect of ASCs on pulmonary fibrosis induced by repetitive bleomycin administration. Further studies will be required to evaluate the efficacy of ASC therapy for the treatment of idiopathic pulmonary fibrosis.

Autologous grafting of non manupulated freshly isolated - adipose tissue derived stromal vascular fraction in single surgical sitting for treatment of knee osteoarthritis

“…30,31 Advantages of SVF include (1) ease of obtaining cells from lipoaspirates, (2) larger pool of adipose derived mesenchymal cells compared with the pool of bone marrow-derived mesenchymal cells (BM-MC) and (3) stronger angiogenic and regenerative potential of adipose derived mesenchymal cells compared with bone marrow derived mesenchymal cells. 32 In this study, all patients showed improved joint function after 12 months. The pain score decreased from 8.1±0.5 before injection to 4.3±0.6 at 6 months, 2.7±0.5 at 9 months and 1.5±0.5 at 12 months after injection.…”

Therapeutic benefits of young, but not old, adipose-derived mesenchymal stem cells in a chronic mouse model of bleomycin-induced pulmonary fibrosis

“…One study reported the use of BM-MSCs in acute lung injury using aged mice, [19] and another used ASCs in young BLM-treated mice. [40] Although expression of tissue factor-4 (TF-4) has been reported to be higher after ASC treatment, [61] raising concerns regarding the development of pulmonary emboli, we found no differences in lung TF-4 mRNA expression between any of the mice. Ongoing studies are currently comparing BM-MSCs and ASCs in aged mice.…”

“…Although several studies have sought to halt fibrosis in the BLM model, they employed male and female mice younger than 12 weeks as recipients and young stem cell donors. [6, 7, 9, 25, 40–42] Previously it has been proposed that BM-MSC therapy inhibits the progression of BLM-induced pulmonary fibrosis by altering both the inflammatory response and collagen deposition [6, 7, 9, 40] – an effect found to be age-dependent in pooled BM-MSCs isolated from young and aged mice and utilized in an LPS lung injury model of ARDS. [19] It should be noted however, that this study by Bustos et al did not directly address the fibrotic process.…”

Human Adipose-derived Mesenchymal Stem Cells Attenuate Early Stage of Bleomycin Induced Pulmonary Fibrosis: Comparison with Pirfenidone

“…The available literature on MSC administration in the bleomycin model supports the concept that administration of MSCs during the acute inflammation provoked by bleomycin effectively decreases the inflammation and inhibits subsequent development of fibrosis (18, 29, 30, 37). There is no available data suggesting that MSC administration once fibrosis is established will decrease fibrosis, rather several studies suggested that MSCs administration at the fibrotic lungs may not be effective, rather may increase lung fibrosis (27, 38, 39).…”

“…In the present study, we have shown than AD-MSCs are efficacious in ameliorating the symptoms of pulmonary fibrosis by increasing survivability and protection from lung fibrosis comparatively better than pirfenidone. Earlier two studies also showed that AD-MSCs relived IPF and provide significant contribution to lung repair at an early stage of disease (16, 18), however, one study did not show any beneficial effect of intra-venous infusion of AD-MSCs either at 0 day or 14 day post bleomycin challenge in lung repair (27). Many studies have reported beneficial effects from MSCs derived from bone marrow, umbilical cord, and amniotic fluid for bleomycin induced lung injury in mice or rat model (28–30).…”