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Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Case Report

First Report in a Human of Successful Treatment of Asthma with Mesenchymal Stem Cells: A Case Report with Review of Literature

Author(s): Joshua Sharan, Amir Barmada, Nicolas Band, Eliana Liebman and Chadwick Prodromos*

Volume 18, Issue 7, 2023

Published on: 13 December, 2022

Page: [1026 - 1029] Pages: 4

DOI: 10.2174/1574888X18666221115141022

Price: $65

Abstract

Introduction: Asthma is a heterogeneous disorder characterized by chronic airway inflammation resulting in obstructive pulmonary symptoms. In preclinical studies, mesenchymal stem cells (MSCs) have demonstrated the ability to ameliorate the symptoms and immunologic pathways seen in asthma.

Due to the known relationship between asthma and the hyper-responsive immune cascade, we hypothesized that MSCs could be an effective treatment option for patients with asthma due to their significant immunomodulatory properties.

Objective: We present the initial results for the first patient enrolled in a phase 1 clinical trial (Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cell Intravenous Infusion for the Treatment of Pulmonary Diseases).

Case Report: A 68-year-old male with a longstanding history of asthma requested mesenchymal stem cell treatment for his persistent asthma symptoms. Cultured umbilical cord-derived mesenchymal stem cells were infused intravenously at a dose of 100 million cells over a period of 40 minutes. Post-treatment follow- up was performed after two and six months.

Results: The patient had no adverse events or complications related to treatment. In the two months posttreatment, his usage of a rescue inhaler decreased to 1 time per month, over 90% reduction. In addition, he had a 70% reduction in nebulizer usage. Improvement was sustained in the 6 months follow-up.

Conclusion: We report the first case of mesenchymal stem cell treatment significantly and safely improving asthma clinical symptoms in a human. Additionally, an extensive literature review provided several plausible mechanisms by which stem cells can ameliorate immune hyper-stimulation associated with asthma.

Keywords: Mesenchymal stem cells, stem cell, asthma, chronic airway inflammation, pulmonary disease, atopy.

Graphical Abstract
[1]
Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med 2012; 18(5): 716-25.
[http://dx.doi.org/10.1038/nm.2678] [PMID: 22561835]
[2]
Barnes PJ. Cellular and molecular mechanisms of asthma and COPD. Clin Sci (Lond) 2017; 131(13): 1541-58.
[http://dx.doi.org/10.1042/CS20160487] [PMID: 28659395]
[3]
Kuruvilla ME, Vanijcharoenkarn K, Shih JA, Lee FEH. Epidemiology and risk factors for asthma. Respir Med 2019; 149: 16-22.
[http://dx.doi.org/10.1016/j.rmed.2019.01.014] [PMID: 30885424]
[4]
Ionescu LI, Alphonse RS, Arizmendi N, et al. Airway delivery of soluble factors from plastic-adherent bone marrow cells prevents murine asthma. Am J Respir Cell Mol Biol 2012; 46(2): 207-16.
[http://dx.doi.org/10.1165/rcmb.2010-0391OC] [PMID: 21903873]
[5]
Masoli M, Fabian D, Holt S, Beasley R. The global burden of asthma: executive summary of the GINA Dissemination Committee Report. Allergy 2004; 59(5): 469-78.
[http://dx.doi.org/10.1111/j.1398-9995.2004.00526.x] [PMID: 15080825]
[6]
Mims JW. Asthma: definitions and pathophysiology. Int Forum Allergy Rhinol 2015; 5(S1) (Suppl. 1): S2-6.
[http://dx.doi.org/10.1002/alr.21609] [PMID: 26335832]
[7]
Toskala E, Kennedy DW. Asthma risk factors. Int Forum Allergy Rhinol 2015; 5 Suppl 1(Suppl 1): S11-6.
[http://dx.doi.org/ 10.1002/alr.21557]
[8]
National Asthma Education and Prevention Program, Third Expert Panel on the Diagnosis and Management of Asthma. Expert PanelReport 3: Guidelines for the Diagnosis and Management of Asthma. Bethesda (MD): National Heart, Lung, and Blood Institute (US); 2007 Aug. Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma. Available from: https://www.ncbi.nlm.nih.gov/books/NBK7232/
[9]
Lemanske RF Jr, Busse WW. 6. Asthma. J Allergy Clin Immunol 2003; 111(2) (Suppl.): S502-19.
[http://dx.doi.org/10.1067/mai.2003.94] [PMID: 12592297]
[10]
Trzil JE, Masseau I, Webb TL, et al. Intravenous adipose-derived mesenchymal stem cell therapy for the treatment of feline asthma: a pilot study. J Feline Med Surg 2016; 18(12): 981-90.
[http://dx.doi.org/10.1177/1098612X15604351] [PMID: 26384398]
[11]
Mathias LJ, Khong SML, Spyroglou L, et al. Alveolar macrophages are critical for the inhibition of allergic asthma by mesenchymal stromal cells. J Immunol 2013; 191(12): 5914-24.
[http://dx.doi.org/10.4049/jimmunol.1300667] [PMID: 24249728]
[12]
Cruz FF, Borg ZD, Goodwin M, et al. Freshly thawed and continuously cultured human bone marrow-derived mesenchymal stromal cells comparably ameliorate allergic airways inflammation in immunocompetent mice. Stem Cells Transl Med 2015; 4(6): 615-24.
[http://dx.doi.org/10.5966/sctm.2014-0268] [PMID: 25925837]
[13]
Papi A, Blasi F, Canonica GW, Morandi L, Richeldi L, Rossi A. Treatment strategies for asthma: reshaping the concept of asthma management. Allergy Asthma Clin Immunol 2020; 16(1): 75.
[http://dx.doi.org/10.1186/s13223-020-00472-8] [PMID: 32944030]
[14]
Hanania NA, Chapman KR, Kesten S. Adverse effects of inhaled corticosteroids. Am J Med 1995; 98(2): 196-208.
[http://dx.doi.org/10.1016/S0002-9343(99)80404-5] [PMID: 7847437]
[15]
Averyanov A, Koroleva I, Konoplyannikov M, et al. First-in-human high-cumulative-dose stem cell therapy in idiopathic pulmonary fibrosis with rapid lung function decline. Stem Cells Transl Med 2020; 9(1): 6-16.
[http://dx.doi.org/10.1002/sctm.19-0037] [PMID: 31613055]
[16]
Fishman JE, Kim GJ, Kyeong NY, Goldin JG, Glassberg MK. Intravenous stem cell dose and changes in quantitative lung fibrosis and DLCO in the AETHER trial: a pilot study. Eur Rev Med Pharmacol Sci 2019; 23(17): 7568-72.
[http://dx.doi.org/10.26355/eurrev_201909_18877] [PMID: 31539148]
[17]
Stolk J, Broekman W, Mauad T, et al. A phase I study for intravenous autologous mesenchymal stromal cell administration to patients with severe emphysema. QJM 2016; 109(5): 331-6.
[http://dx.doi.org/10.1093/qjmed/hcw001] [PMID: 26819296]
[18]
Le Thi Bich P, Nguyen Thi H, Dang Ngo Chau H, et al. Allogeneic umbilical cord-derived mesenchymal stem cell transplantation for treating chronic obstructive pulmonary disease: a pilot clinical study. Stem Cell Res Ther 2020; 11(1): 60.
[http://dx.doi.org/10.1186/s13287-020-1583-4] [PMID: 32054512]
[19]
Sinyor B, Concepcion Perez L. Pathophysiology of Asthma.StatPearls. Treasure Island, FL: StatPearls Publishing 2021.
[20]
Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005; 105(4): 1815-22.
[http://dx.doi.org/10.1182/blood-2004-04-1559] [PMID: 15494428]
[21]
Ghannam S, Pène J, Torcy-Moquet G, Jorgensen C, Yssel H. Mesenchymal stem cells inhibit human Th17 cell differentiation and function and induce a T regulatory cell phenotype. J Immunol 2010; 185(1): 302-12.
[http://dx.doi.org/10.4049/jimmunol.0902007] [PMID: 20511548]
[22]
Prevosto C, Zancolli M, Canevali P, Zocchi MR, Poggi A. Generation of CD4+ or CD8+ regulatory T cells upon mesenchymal stem cell-lymphocyte interaction. Haematologica 2007; 92(7): 881-8.
[http://dx.doi.org/10.3324/haematol.11240] [PMID: 17606437]
[23]
Théry C, Amigorena S. The cell biology of antigen presentation in dendritic cells. Curr Opin Immunol 2001; 13(1): 45-51.
[http://dx.doi.org/10.1016/S0952-7915(00)00180-1] [PMID: 11154916]
[24]
Jiang XX, Zhang Y, Liu B, et al. Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood 2005; 105(10): 4120-6.
[http://dx.doi.org/10.1182/blood-2004-02-0586] [PMID: 15692068]
[25]
Xu M, Li X, Ma C, Lü Y, Ma X, Ma X. Effect of human placental mesenchymal stem cells transplantation on pulmonary vascular endothelial permeability and lung injury repair in mice with acute lung injury. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2020; 343: 387-92.
[http://dx.doi.org/10.7507/1002-1892.201909070]
[26]
Krystel-Whittemore M, Dileepan KN, Wood JG. Mast cell: A multi-functional master cell. Front Immunol 2016; 6: 620.
[http://dx.doi.org/10.3389/fimmu.2015.00620] [PMID: 26779180]

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