Respirology. 2016 Sep 29. doi: 10.1111/resp.12911. [Epub ahead of print]
Mesenchymal stem cells in the treatment of chronic lung disease.
1Dorothy P. & Richard P. Simmons Center for Interstitial Lung Disease, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
2Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
3Dorothy P. & Richard P. Simmons Center for Interstitial Lung Disease, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. firstname.lastname@example.org.
4Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. email@example.com.
5Vascular Medicine Institute of the University of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Mesenchymal stem cells (MSCs) are a populace of non-hematopoietic 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.
Chronic lung disease; lung injury; mesenchymal stem cell; therapy
Stem Cell Rev. 2012 Dec;8(4):1236-44. doi: 10.1007/s12015-012-9410-7.
Experimental basis and new insights for cell therapy in Chronic Obstructive Pulmonary Disease.
1Program of Post-Graduation in Genetics, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Chronic Obstructive Pulmonary Disease (COPD) can be briefly described as air flow limitation and chronic dyspnea associated to an inflammatory response of the respiratory tract to noxious particles and gases. Its main feature is the obstruction of airflow and consequent chronic dyspnea. Despite recent advances, and the development of new therapeutic, medical and clinical approaches, a curative therapy is yet to be achieved. Therapies involving the use of tissue-specific or donor derived cells present a promising alternative in the treatment of degenerative diseases and injuries. Recent studies demonstrate that mesenchymal stem cells have the capacity to modulate immune responses in acute lung injury andpulmonary fibrosis in animal models, as well as in human patients. Due to these aspects, different groups raised the possibility that the stem cellsfrom different sources, such as those found in bone marrow or adipose tissue, could act preventing the emphysematous lesion progression. In this paper, it is proposed a review of the current state of the art and future perspectives on the use of cell therapy in obstructive lung diseases.
Keywords: Chronic obstructive pulmonary disease; Cell therapy; Stem cells; Bone marrow
Iran J Allergy Asthma Immunol. 2015 Dec;14(6):552-68.
Therapeutic Potential of Mesenchymal Stem Cells for the Treatment of Airway Remodeling in Pulmonary Diseases.
1Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
2Department of Immunology, Pasteur Institute of Iran, Tehran, Iran.
3National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran.
According to significant improvements in the tissue engineering field over the past several years, lung tissue cells have recently attracted more attention due to the high prevalence and diversity in related diseases. However, selection of an appropriate cell type, screening of suitable conditions for growth and proliferation, as well as subsequent implantation into the body to repair and regenerate damaged tissues are considered as important issues in this context. It should also be noted that most studies have been described in animal models, but not in humans. Because of the high regenerative capacity, predominant immunomodulatory feature, and inhibition of T-lymphocyte proliferation, mesenchymal stem cells (MSCs) may play an important role in the reconstruction of damaged tissues including bronchioles in pulmonary diseases. Interestingly, clinical trial studies demonstrated that MSCs have the significant potential to treat a wide variety of diseases including acute myocardial infarction (AMI), liver cirrhosis, crohn’s disease, and graft-versus-host disease (GVHD).
Adipose-derived mesenchymal stem cell; Airway remodeling; Chronic bronchitis; Chronic obstructive pulmonary disease; Inflammation; Lung diseases; Mesenchymal stem cell
PLoS One. 2016 Jun 9. doi: 10.1371/journal.pone.0157099
Preclinical Studies of Mesenchymal Stem Cell (MSC) Administration in Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review and Meta-Analysis
Liu X1, Fang Q2, Kim H3.
1Pulmonary, Critical Care, Sleep and Allergy Medicine, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, United States of America
2Department of Pulmonary and Critical Care, Beijing Chaoyang Hospital, The Capital Medical University, Beijing, China
3Pulmonary and Critical Care Division, WonKwang University, Sanbon Medical Center, Seoul, Korea
In the last two decades, mesenchymal stem cells (MSCs) have been pre-clinically utilized in the treatment of a variety of kinds of diseases including chronic obstructive pulmonary disease (COPD). The aim of the current study was to systematically review and conduct a meta-analysis on the published pre-clinical studies of MSC administration in the treatment of COPD in animal models.
Methods and Results
A systematic search of electronic databases was performed. Statistical analysis was performed using the Comprehensive Meta-Analysis software (Version 3). The pooled Hedges’s g with 95% confidence intervals (95% CIs) was adopted to assess the effect size. Random effect model was used due to the heterogeneity between the studies. A total of 20 eligible studies were included in the current systematic review. The overall meta-analysis showed that MSC administration was significantly in favor of attenuating acute lung injury (Hedges’s g = -2.325 ± 0.145 with 95% CI: -2.609 ~ -2.040, P < 0.001 for mean linear intercept, MLI; Hedges’s g = -3.488 ± 0.504 with 95% CI: -4.476 ~ -2.501, P < 0.001 for TUNEL staining), stimulating lung tissue repair (Hedges’s g = 3.249 ± 0.586 with 95% CI: 2.103~ 4.394, P < 0.001) and improving lung function (Hedges’s g = 2.053 ± 0.408 with 95% CI: 1.253 ~ 2.854, P< 0.001). The mechanism of MSC therapy in COPD is through ameliorating airway inflammation (Hedges’s g = -2.956 ± 0.371 with 95% CI: -3.683 ~ -2.229, P< 0.001) and stimulating cytokine synthesis that involves lung tissue repair (Hedges’s g = 3.103 ± 0.734 with 95% CI: 1.664 ~ 4.541, P< 0.001).
This systematic review and meta-analysis suggest a promising role for MSCs in COPD treatment. Although the COPD models may not truly mimic COPD patients, these pre-clinical studies demonstrate that MSC hold promise in the treatment of chronic lung diseases including COPD. The mechanisms of MSCs role in preclinical COPD treatment may be associated with attenuating airway inflammation as well as stimulating lung tissue repair.