Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Critical Care
Published in: Critical Care 1/2018

Open Access 01-12-2018 | Research

Intrapulmonary autologous transplant of bone marrow-derived mesenchymal stromal cells improves lipopolysaccharide-induced acute respiratory distress syndrome in rabbit

Authors: Mohammad Reza Mokhber Dezfouli, Massoumeh Jabbari Fakhr, Sirous Sadeghian Chaleshtori, Mohammad Mehdi Dehghan, Alireza Vajhi, Roshanak Mokhtari

Published in: Critical Care | Issue 1/2018

Login to get access

Abstract

Background

Lung diseases such as acute respiratory distress syndrome (ARDS) have a high incidence worldwide. The current drug therapies for ARDS have supportive effects, making them inefficient. New methods such as stromal cell therapy are needed for this problem.

Methods

This research was performed with ten New Zealand rabbits in two groups. Bone marrow aspiration was performed on the treated group, and mesenchymal stem cells were isolated and cultured. The experimental model of ARDS was induced using LPS from Escherichia coli strain O55:B5. Then, 1010 bone marrow mesenchymal stem cells (BM-MSCs) were autologously transplanted intrapulmonary in the treatment group, and 1–2 ml of PBS in the control group. The clinical signs, computed tomographic (CT) scans, echocardiography, blood gas analysis, complete blood count, and cytokine levels were measured before and at 3, 6, 12, 24, 48, 72, and 168 h after BM-MSC transplant. Finally, the rabbits were killed, and histopathological examination was performed.

Results

The results showed that BM-MSCs decreased the severity of clinical symptoms, the number of white blood cells and heterophils in the blood, the total cell count, and number of heterophils and macrophages in bronchoalveolar lavage, and balanced the values of arterial blood gases (increase in partial pressure of oxygen and O2 saturation and decrease in the partial pressure of carbon dioxide). They also downregulated the tumor necrosis factor (TNF)-α and interleukin (IL)-6 concentrations and increased the IL-10 concentrations at different times compared with time 0 and in the control group, significantly. In the CT scan, a significant decrease in the Hounsfield units and total lung volume was found by echocardiography, and in comparing the two groups, a significant difference in the parameters was noticed. The histopathology demonstrated that the BM-MSCs were able to reduce the infiltration of inflammatory cells and pulmonary hemorrhage and edema.

Conclusions

This study indicated that BM-MSCs play a significant role in the repair of lung injury.
Appendix
Available only for authorised users
Literature
1.
ARDS Definition Task Force, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23):2526–33.
2.
Bernard GR, Artigas A. The definition of ARDS revisited: 20 years later. Intensive Care Med. 2016;42(5):640–2.CrossRef
3.
Gonzales JN, Lucas R, Verin AD. The acute respiratory distress syndrome: mechanisms and perspective therapeutic approaches. Austin J Vasc Med. 2015;2(1):1009.PubMedPubMedCentral
4.
Matthay MA, Zemans RL. The acute respiratory distress syndrome: pathogenesis and treatment. Annu Rev Pathol. 2011;6:147–63.CrossRef
5.
Cruz FF, Weiss DJ, Rocco PR. Prospects and progress in cell therapy for acute respiratory distress syndrome. Expert Opin Biol Ther. 2016;16(11):1353–60.CrossRef
6.
Dushianthan A, Grocott MPW, Postle AD, Cusack R. Acute respiratory distress syndrome and acute lung injury. Postgrad Med J. 2011;87(1031):612–22.CrossRef
7.
McIntyre LA, Moher D, Fergusson DA, Sullivan KJ, Mei SH, Lalu M, Marshall J, McLeod M, Griffin G, Grimshaw J, et al. Efficacy of mesenchymal stromal cell therapy for acute lung injury in preclinical animal models: a systematic review. PLoS One. 2016;11(1):e0147170.CrossRef
8.
Bein T, Grasso S, Moerer O, Quintel M, Guerin C, Deja M, Brondani A, Mehta S. The standard of care of patients with ARDS: ventilatory settings and rescue therapies for refractory hypoxemia. Intensive Care Med. 2016;42(5):699–711.CrossRef
9.
Abbasi J, Mokhber Dezfouli MR, Sadeghian Chaleshtori S, Dehghan MM, Vajhi A, Baharvand H, Ghanei M, Jabari Fakhr M. Improvement of clinical signs in experimental model of acute respiratory distress syndrome (ARDS) in sheep following autograft of bone marrow-derived mesenchymal stem cells (BM-MSCs). J Vet Res. 2018;73:17–26.
10.
Mokhber Dezfouli MR, Sadeghian Chaleshtori S, Moradmand A, Basiri M, Baharvand H, Tahamtani Y. Hydrocortisone promotes differentiation of mouse embryonic stem cell-derived definitive endoderm toward lung alveolar epithelial cells. Cell J. 2019;20(4):469–76.PubMed
11.
Dezfouli MR, Chaleshtori SS, Dehghan MM, Tavanaeimanesh H, Baharvand H, Tahamtani Y. The therapeutic potential of differentiated lung cells from embryonic stem cells in lung diseases. Curr Stem Cell Res Ther. 2017;12(1):80–4.CrossRef
12.
Sadeghian Chaleshtori S, Dezfouli MR, Dehghan MM, Tavanaeimanesh H. Generation of lung and airway epithelial cells from embryonic stem cells in vitro. Crit Rev Eukaryot Gene Expr. 2016;26(1):1–9.CrossRef
13.
Matthay MA. Therapeutic potential of mesenchymal stromal cells for acute respiratory distress syndrome. Ann Am Thorac Soc. 2015;12(Suppl 1):S54–7.CrossRef
14.
Sdrimas K, Kourembanas S. MSC microvesicles for the treatment of lung disease: a new paradigm for cell-free therapy. Antioxid Redox Signal. 2014;21(13):1905–15.CrossRef
15.
Goolaerts A, Pellan-Randrianarison N, Larghero J, Vanneaux V, Uzunhan Y, Gille T, Dard N, Planès C, Matthay MA, Clerici C. Conditioned media from mesenchymal stromal cells restore sodium transport and preserve epithelial permeability in an in vitro model of acute alveolar injury. Am J Physiol Lung Cell Mol Physiol. 2014;306(11):L975–85.CrossRef
16.
Slutsky AS, Villar J, Pesenti A. Happy 50th birthday ARDS! Intensive Care Med. 2016;42(5):637–9.CrossRef
17.
Kamaruzaman NA, Kardia E, Kamaldin N’, Latahir AZ, Yahaya BH. The rabbit as a model for studying lung disease and stem cell therapy. Biomed Res Int. 2013;2013:691830.CrossRef
18.
Mei SH, Dos Santos CC, Stewart DJ. Advances in stem cell and cell-based gene therapy approaches for experimental acute lung injury: a review of preclinical studies. Hum Gene Ther. 2016;27(10):802–12.CrossRef
19.
Gao X, Chen W, Liang Z, Chen L. Autotransplantation of circulating endothelial progenitor cells protects against lipopolysaccharide-induced acute lung injury in rabbit. Int Immunopharmacol. 2011;11(10):1584–90.CrossRef
20.
Zhu F, Guo GH, Chen W, Peng Y, Xing JJ, Wang NY. Effect of bone marrow-derived mesenchymal stem cells transplantation on the inflammatory response and lung injury in rabbit with inhalation injury [in Chinese]. Zhonghua Shao Shang Za Zhi. 2010;26(5):360–5.PubMed
21.
Fang X, Abbott J, Cheng L, Colby JK, Lee JW, Levy BD, Matthay MA. Human mesenchymal stem (stromal) cells promote the resolution of acute lung injury in part through lipoxin A4. J Immunol. 2015;195(3):875–81.CrossRef
22.
Kavanagh DP, Robinson J, Kalia N. Mesenchymal stem cell priming: fine-tuning adhesion and function. Stem Cell Rev. 2014;10(4):587–99.CrossRef
23.
Loebinger MR, Aguilar S, Janes SM. Therapeutic potential of stem cells in lung disease: progress and pitfalls. Clin Sci (Lond). 2008;114(2):99–108.CrossRef
24.
Burnham EL, Janssen WJ, Riches DW, Moss M, Downey GP. The fibroproliferative response in acute respiratory distress syndrome: mechanisms and clinical significance. Eur Respir J. 2014;43(1):276–85.CrossRef
25.
Zhu H, Xiong Y, Xia Y, Zhang R, Tian D, Wang T, Dai J, Wang L, Yao H, Jiang H, et al. Therapeutic effects of human umbilical cord-derived mesenchymal stem cells in acute lung injury mice. Sci Rep. 2017;7:39889.CrossRef
26.
Gupta N, Su X, Popov B, Lee JW, Serikov V, Matthay MA. Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J Immunol. 2007;179(3):1855–63.CrossRef
27.
Moodley Y, Sturm M, Shaw K, Shimbori C, Tan DBA, Kolb M, Graham R. Human mesenchymal stem cells attenuate early damage in a ventilated pig model of acute lung injury. Stem Cell Res. 2016;17(1):25–31.
28.
Monsel A, Zhu YG, Gennai S, Hao Q, Hu S, Rouby JJ, Rosenzwajg M, Matthay MA, Lee JW. Therapeutic effects of human mesenchymal stem cell-derived microvesicles in severe pneumonia in mice. Am J Respir Crit Care Med. 2015;192(3):324–36.CrossRef
29.
Li Y, Xu J, Shi W, Chen C, Shao Y, Zhu L, Lu W, Han X. Mesenchymal stromal cell treatment prevents H9N2 avian influenza virus-induced acute lung injury in mice. Stem Cell Res Ther. 2016;7:159.CrossRef
30.
Devaney J, Horie S, Masterson C, Elliman S, Barry F, O’Brien T, Curley GF, O’Toole D, Laffey JG. Human mesenchymal stromal cells decrease the severity of acute lung injury induced by E. coli in the rat. Thorax. 2015;70(7):625–35.CrossRef
31.
Zhou J, Jiang L, Long X, Fu C, Wang X, Wu X, Liu Z, Zhu F, Shi J, Li S. Bone-marrow-derived mesenchymal stem cells inhibit gastric aspiration lung injury and inflammation in rats. J Cell Mol Med. 2016;20(9):1706–17.CrossRef
32.
Xiang B, Chen L, Wang X, Zhao Y, Wang Y, Xiang C. Transplantation of menstrual blood-derived mesenchymal stem cells promotes the repair of LPS-induced acute lung injury. Int J Mol Sci. 2017;18(4):E689.CrossRef
33.
Pedrazza L, Cunha AA, Luft C, Nunes NK, Schimitz F, Gassen RB, Breda RV, Donadio MVF, de Souza Wyse AT, Pitrez PMC, Rosa JL, de Oliveira JR. Mesenchymal stem cells improves survival in LPS-induced acute lung injury acting through inhibition of NETs formation. J Cell Physiol. 2017;232(12):3552–64.
34.
Shi Y, Su J, Roberts AI, Shou P, Rabson AB, Ren G. How mesenchymal stem cells interact with tissue immune responses. Trends Immunol. 2012;33(3):136–43.CrossRef
35.
Caironi P, Carlesso E, Gattinoni L. Radiological imaging in acute lung injury and acute respiratory distress syndrome. Semin Respir Crit Care Med. 2006;27(4):404–15.CrossRef
36.
Gattinoni L, Caironi P, Valenza F, Carlesso E. The role of CT-scan studies for the diagnosis and therapy of acute respiratory distress syndrome. Clin Chest Med. 2006;27(4):559–70.CrossRef
Metadata
Title
Intrapulmonary autologous transplant of bone marrow-derived mesenchymal stromal cells improves lipopolysaccharide-induced acute respiratory distress syndrome in rabbit
Authors
Mohammad Reza Mokhber Dezfouli
Massoumeh Jabbari Fakhr
Sirous Sadeghian Chaleshtori
Mohammad Mehdi Dehghan
Alireza Vajhi
Roshanak Mokhtari
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2018
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-018-2272-x

Other articles of this Issue 1/2018

Critical Care 1/2018 Go to the issue

Research

Feasibility of biventricular 3D transthoracic echocardiography in the critically ill and comparison with conventional parameters

Research

Indicators of intensive care unit capacity strain: a systematic review

Research

Corticosteroid use and intensive care unit-acquired weakness: a systematic review and meta-analysis

Research

Identification of subclasses of sepsis that showed different clinical outcomes and responses to amount of fluid resuscitation: a latent profile analysis

Research

Cost-effectiveness study of early versus late parenteral nutrition in critically ill children (PEPaNIC): preplanned secondary analysis of a multicentre randomised controlled trial

Letter

Cardiac output and CVP monitoring… to guide fluid removal