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Deaths caused by lung disease have not decreased over past decade, shows UK study

BMJ 2016; 353 doi: https://doi.org/10.1136/bmj.i3044 (Published 31 May 2016) Cite this as: BMJ 2016;353:i3044

Cell therapy may be the answer Re: Deaths caused by lung disease have not decreased over past decade, shows UK study

Despite recent advances in the fields of pre-clinical and clinical sciences, we are painfully conscious to come across such an insightful article [1] that revealed our inefficiencies in developing effective therapies to cure patients suffering from desperate lung diseases and incurable lung cancers.

An estimated 65 million people suffer from moderate to severe chronic obstructive pulmonary disease (COPD), from which about 3 million die each year, making it the third leading cause of death worldwide – and the numbers are increasing. [2]

COPD is characterized by chronic inflammation in the lung parenchyma as a response to inhaled noxious particles, emphysema, fibrosis and mucus hypersecretion, resulting in progressive expiratory airflow obstruction [3]. Only symptomatic treatment is available for COPD.

Mesenchymal stem/stromal cells (MSCs) have been shown to possess anti-inflammatory and anti-fibrotic properties due to the secretion of various cytokines and soluble factors, which affect a variety of immune cells and promote tissue regeneration [4, 5].

Due to the tissue-regenerative and immune-modulatory properties, extensive pre-clinical studies have been conducted on MSC-based products in animal models of COPD. Since cell therapies represent multimodal therapeutic agents with the ability to influence immune and regenerative functions [6], they are accepted as promising treatment options for various degenerative lung diseases.

Numerous preclinical studies demonstrate an improvement of disease-associated parameters after MSC administration in several lung disorders, including chronic obstructive pulmonary disease, acute respiratory distress syndrome and idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis is known as progressive, irreversible lung disease associated with accumulation of fibroblasts in the parenchyma that results in characteristic fibrotic scar formation and with alterations in lung tissue architecture characterized by destroyed lung tissue containing numerous cystic airspaces with thick fibrous walls, referred to as honeycombing. In most cases, the disease trigger is unknown, but a link to impaired wound healing after recurrent epithelial injuries is assumed [7].Due to limited treatment options, the prognosis is often poor with a median survival time of ∼3 years after diagnosis [8].

On the other hand, the most common lethal neoplasm in the world is lung cancer, which kills 1.6 million people each year. On average, 78 Canadians were diagnosed with lung cancer every day. On average, 58 Canadians died from lung cancer every day. [9]

Despite several unanswered basic science questions regarding optimal timing of delivery, the number of cells needed, and the mechanism of homing etc., the success report of MSc as documented in vivo such as reduction in tumor growth, elimination of metastases and improvement in survival, has produced remarkable excitement that cell therapy may have promising clinical applications [10].

Conclusion:
Extensive in-depth pre-clinical research studies to describe new modalities of cell therapies are urgently needed for a series of desperate lung diseases including incurable lung cancer cases, which may drive pre-clinical research outcome to the clinic.

Recent advances in cell-based therapies for lung diseases are evolving at a rapid space to become promising, viable and safe treatment options for clinical application (http://ow.ly/oXe130crWmw).

Reference:
1. Deaths caused by lung disease have not decreased over past decade, shows UK study: BMJ 2016; 353
doi: https://doi.org/10.1136/bmj.i3044 (Published 31 May 2016) Cite this as: BMJ 2016;353:i3044.
2. The Global Impact of Respiratory Disease - World Health Organization:www.who.int/gard/publications/The_Global_Impact_of_Respiratory_Disease.pdf
3. Lomas DA. Does protease-antiprotease imbalance explain chronic obstructive pulmonary disease? Ann Am Thorac Soc 2016; 13: Suppl. 2, S130–S137.
4. Bernardo ME, Fibbe WE. Mesenchymal stromal cells: sensors and switchers of inflammation. Cell Stem Cell 2013; 13: 392–402
5. Shi Y, Hu G, Su J, et al. Mesenchymal stem cells: a new strategy for immunosuppression and tissue repair. Cell Res 2010; 20: 510–518.
6. Weiss DJ. Concise review: current status of stem cells and regenerative medicine in lung biology and diseases. Stem Cells 2014; 32: 16–25.
7. Cahill EF, Kennelly H, Carty F, et al. Hepatocyte growth factor is required for mesenchymal stromal cell protection against bleomycin-induced pulmonary fibrosis. Stem Cells Transl Med 2016; 5: 1307–1318.
8. Lan YW, Choo KB, Chen CM, et al. Hypoxia-preconditioned mesenchymal stem cells attenuate bleomycin-induced pulmonary fibrosis. Stem Cell Res Ther 2015; 6: 97.
9. Lung cancer statistics are estimates from: Canadian Cancer Society's Steering Committee: Canadian Cancer Statistics 2017. Toronto: Canadian Cancer Society, 2017. http://www.cancer.ca/en/cancer-information/cancer-type/lung/statistics/?....
10. Bernardo ME, Zaffaroni N, Novara F, et al. Human bone marrow derived mesenchymal stem cells do not undergo transformation after long-term in vitro culture and do not exhibit telomere maintenance mechanisms. Cancer Res 2007; 67: 9142–9.

Competing interests: No competing interests

22 December 2018
Prof. Dr. Jogenananda Pramanik
Professor and Dean
Dr. Azzard Comrie, Senior Medical Officer, Hargreaves Hospital, Mandeville; Dr Clive C. Lloyd, Consultant General Surgeon; Regional Hospital, Mandeville, Manchester, Jamaica, WI. Prof. Dr. Narazah Mohd Yuseff and Prof. Dr Badrul Hisham Yahaya, Universiti Sains Malaysia.
Careers Abroad Institute School of Medicine, Mandeville, Manchester, Jamaica,WI.
32, Hargreaves Avenue (Hargreaves Medical Complex) Mandeville, Manchester, Jamaica, West Indies.