Abstract
BackgroundThe present study compared the effects of antifibrotic medications, pirfenidone, and nintedanib, with transplantation of human umbilical mesenchymal stem cells (HUMSCs) in restoring rat pulmonary fibrosis (PF).MethodsA stable animal model was established via an intratracheal injection of 5 mg bleomycin (BLM). One single transplantation of 2.5× 107 HUMSCs or initiation of daily oral nintedanib/pirfenidone administration was performed on day 21 following BLM damage.ResultsPulmonary function examination revealed that BLM rats exhibited a significant decrease in blood oxygen saturation and an increase in respiratory rates. While no significant improvements were found in BLM rats receiving nintedanib or pirfenidone, those who transplanted with HUMSCs showed a statistical amelioration in blood oxygen saturation and significant alleviation in respiratory rates. Quantification results revealed that a significant reduction in alveolar space and marked increases in substantial cell infiltration and collagen deposition in the left lungs of BLM rats. No significant alteration was observed in BLM rats administered nintedanib or pirfenidone. However, BLM rats transplanted with HUMSCs had a significant recovery in alveolar space and noticeable decreases in cell infiltration and collagen deposition. The inflammatory cell numbers in the bronchoalveolar lavage was increased in the BLM group. While the rats treated with nintedanib or pirfenidone had a lower cell number than the BLM group, a higher cell number was found as compared with the Normal group. In rats transplanted with HUMSCs, the cell number did not differ from the Normal group.ConclusionsTransplantation of HUMSCs could effectively treat PF as opposed to the administration of anti-fibrotic drugs with nintedanib or pirfenidone with a significant better result in lung volume, pathological changes, lung function, and blood oxygen saturation.
Highlights
A number of risk factors can result in the destruction of the lung tissues
Lung impairment triggers the number of functional alveoli to decrease, and the alveolar compartments are gradually replaced by fibrotic tissues, leading to the development of pulmonary fibrosis (PF)
In order to precisely evaluate the effect of medications or xenografted stem cells in treating PF in rat, our laboratory has previously established a severe, reproducible, consistent, one-sided left-lung fibrosis animal model, which provides advantages in keeping the rat alive and allowing accurate evaluations of the therapeutic effects of human umbilical mesenchymal stem cells from Wharton’s jelly (HUMSCs) for rat PF [9]
Summary
A number of risk factors can result in the destruction of the lung tissues. Lung impairment triggers the number of functional alveoli to decrease, and the alveolar compartments are gradually replaced by fibrotic tissues, leading to the development of pulmonary fibrosis (PF). Intratracheal injection of BLM was most extensively applied due to its relatively short period of disease progression, and the pathological condition closely resembles patients with idiopathic PF. The severity of damage caused by the intratracheal injection of BLM to each lobe of the lung varies from experiment to experiment. In order to precisely evaluate the effect of medications or xenografted stem cells in treating PF in rat, our laboratory has previously established a severe, reproducible, consistent, one-sided left-lung fibrosis animal model, which provides advantages in keeping the rat alive and allowing accurate evaluations of the therapeutic effects of human umbilical mesenchymal stem cells from Wharton’s jelly (HUMSCs) for rat PF [9]. The present study compared the effects of antifibrotic medications, pirfenidone, and nintedanib, with transplantation of human umbilical mesenchymal stem cells (HUMSCs) in restoring rat pulmonary fibrosis (PF)
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