Stem cell therapy for idiopathic pulmonary fibrosis: How far are we from the bench to the bedside?

Wang, Zheng; Kang, Yi Da; Zeng, Yanli; Li, Hongmei; Chen, Xiaoqian; Ma, Lijun

doi:10.4236/jbise.2013.68a2004

Cited by 5 publications

(5 citation statements)

References 83 publications

(85 reference statements)

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“…In this study, we demonstrated the safety and efficacy of an intrinsic lung‐derived cell therapy product in a bleomycin‐induced rat model of pulmonary fibrosis. Allogeneic cell therapy for lung diseases has been pursued in previous research endeavors and current phase I clinical trials, but almost exclusively with MSCs . In contrast, the use of intrinsic distal lung‐derived cells represents a new approach .…”

Section: Discussionmentioning

confidence: 99%

“…Allogeneic cell therapy for lung diseases has been pursued in previous research endeavors and current phase I clinical trials, but almost exclusively with MSCs . In contrast, the use of intrinsic distal lung‐derived cells represents a new approach . LSCs benefit from a self‐agglomerating 3D sphere culture system which has been shown to recapitulate the in vivo environment and enhance the innate stemness of cells .…”

Section: Discussionmentioning

confidence: 99%

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Safety and Efficacy of Allogeneic Lung Spheroid Cells in a Mismatched Rat Model of Pulmonary Fibrosis

Cores

Hensley

Kinlaw

et al. 2017

Stem Cells Translational Medicine

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Idiopathic pulmonary fibrosis is a devastating interstitial lung disease characterized by the relentless deposition of extracellular matrix causing lung distortions and dysfunctions. The prognosis after detection is merely 3-5 years and the only two Food and Drug Administration-approved drugs treat the symptoms, not the disease, and have numerous side effects. Stem cell therapy is a promising treatment strategy for pulmonary fibrosis. Current animal and clinical studies focus on the use of adipose or bone marrow-derived mesenchymal stem cells. We, instead, have established adult lung spheroid cells (LSCs) as an intrinsic source of therapeutic lung stem cells. In the present study, we compared the efficacy and safety of syngeneic and allogeneic LSCs in immunocompetent rats with bleomycin-induced pulmonary inflammation in an effort to mitigate fibrosis development. We found that infusion of allogeneic LSCs reduces the progression of inflammation and fibrotic manifestation and preserves epithelial and endothelial health without eliciting significant immune rejection. Our study sheds light on potential future developments of LSCs as an allogeneic cell therapy for humans with pulmonary fibrosis. STEM CELLS TRANSLATIONAL MEDICINE 2017;9:1905-1916 SIGNIFICANCE STATEMENTWe have demonstrated the safety and efficacy of allogeneic lung spheroid cell (LSC) treatment in attenuating the progression and severity of pulmonary fibrosis, decreasing apoptosis, protecting alveolar structures, and increasing angiogenesis in rats. The use of allogeneic stem cells can potentially change the way we perform cell therapies by allowing for the growth of large quantities of cells from numerous sources, including donated lungs not used for transplantations, surgical discards, and lungs from recently deceased cadavers. Our study demonstrates the potential of allogeneic LSCs as a viable future therapy option for patients suffering from idiopathic pulmonary fibrosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Safety and Efficacy of Allogeneic Lung Spheroid Cells in a Mismatched Rat Model of Pulmonary Fibrosis

Cores

Hensley

Kinlaw

et al. 2017

Stem Cells Translational Medicine

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“…Idiopathic pulmonary fibrosis (IPF), the most common type of interstitial lung disease (ILD), is a chronic, irreversible disease that is characterized by exaggerated matrix deposition, lung architecture distortion and honeycombing . As the disease progresses, it leads to restricted ventilation, impaired gas exchange, respiratory symptoms, exercise limitation, poor quality of life and ultimately death .…”

Section: Idiopathic Pulmonary Fibrosismentioning

confidence: 99%

“…Of those who received a lung transplant, the median survival time was 55.5 months . The drug pirfenidone has been shown to slow the progression of IPF, but is not able to reverse septa thickening or alveolar distortion . Two recent 52‐week, randomized, phase 3 trials of the drug nintedanib found its use to be associated with a reduced decline in forced vital capacity (FVC), consistent with a slowing of disease progression .…”

Section: Idiopathic Pulmonary Fibrosismentioning

confidence: 99%

Mesenchymal stem cells in the treatment of chronic lung disease

Wecht

Rojas

2016

Respirology

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Mesenchymal stem cells (MSCs) are a populace of nonhaematopoietic multipotent stromal cells, which have the ability to differentiate into tissue derived from a single germ layer. MSCs have been isolated from various sites, including adipose tissue, skeletal muscle, synovium, spleen, thymus, lung and amniotic fluid, but are most often isolated from bone marrow. MSCs have several valuable functions that make them a promising therapeutic option in the field of regenerative medicine, including the secretion of anti-inflammatory cytokines and growth factors, the migration of cells to the site of injury when administered and the ability to 'rescue' cells through the transfer of functional mitochondria. They also offer the possibility of autologous cell transplantation, circumventing immune rejection. These properties, among others, make MSCs a promising potential therapeutic agent in the treatment of chronic lung diseases with high rates of morbidity and mortality, such as idiopathic pulmonary fibrosis (IPF), COPD and obstructive bronchiolitis (OB). Numerous animal models have shown the protective and reparative effects of MSCs in models of experimental lung injury. There are currently several clinical trials underway to evaluate the safety and efficacy of MSCs in the treatment of IPF, COPD and OB. While early results are encouraging, a considerable amount of research must be done concerning the safety MSCs, as well as their optimal dosage, time and route of administration. In addition, much is still unknown about the pathogenesis of these chronic lung diseases, as well as the mechanisms MSCs utilize to assist in their repair.

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“…Idiopathic pulmonary fibrosis (IPF), featured by chronic exacerbating dyspnea and respiratory failure, affects 2–29 cases per 100,000 individuals [ 1 , 2 ]. The mean survival time of IPF after an initial diagnosis, ranging from 3.2 to 5 years, has remained unchanged in recent years despite vast improvement of novel drugs [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Corilagin Attenuates Aerosol Bleomycin-Induced Experimental Lung Injury

Zheng

Guo

Xiao-ju

et al. 2014

IJMS

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Idiopathic pulmonary fibrosis (IPF) is a progressing lethal disease with few clinically effective therapies. Corilagin is a tannin derivative which shows anti-inflammatory and antifibrotics properties and is potentiated in treating IPF. Here, we investigated the effect of corilagin on lung injury following bleomycin exposure in an animal model of pulmonary fibrosis. Corilagin abrogated bleomycin-induced lung fibrosis as assessed by H&E; Masson’s trichrome staining and lung hydroxyproline content in lung tissue. Corilagin reduced the number of apoptotic lung cells and prevented lung epithelial cells from membrane breakdown, effluence of lamellar bodies and thickening of the respiratory membrane. Bleomycin exposure induced expression of MDA, IKKα, phosphorylated IKKα (p-IKKα), NF-κB P65, TNF-α and IL-1β, and reduced I-κB expression in mice lung tissue or in BALF. These changes were reversed by high-dose corilagin (100 mg/kg i.p) more dramatically than by low dose (10 mg/kg i.p). Last, corilagin inhibits TGF-β1 production and α-SMA expression in lung tissue samples. Taken together, these findings confirmed that corilagin attenuates bleomycin-induced epithelial injury and fibrosis via inactivation of oxidative stress, proinflammatory cytokine release and NF-κB and TGF-β1 signaling. Corilagin may serve as a promising therapeutic agent for pulmonary fibrosis.

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Stem cell therapy for idiopathic pulmonary fibrosis: How far are we from the bench to the bedside?

Abstract: ABSTRACT

Cited by 5 publications

References 83 publications

Safety and Efficacy of Allogeneic Lung Spheroid Cells in a Mismatched Rat Model of Pulmonary Fibrosis

Safety and Efficacy of Allogeneic Lung Spheroid Cells in a Mismatched Rat Model of Pulmonary Fibrosis

Mesenchymal stem cells in the treatment of chronic lung disease

Corilagin Attenuates Aerosol Bleomycin-Induced Experimental Lung Injury

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