Stem Cells Translational Medicine
John Wiley & Sons, Inc.
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Mesenchymal stem cells as a potential treatment for critically ill patients with coronavirus disease 2019
Volume: 9 , Issue: 7
Doi: 10.1002/sctm.20-0083
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Ji, Li, Li, Jin, and Liu: Mesenchymal stem cells as a potential treatment for critically ill patients with coronavirus disease 2019

To the Editor,

We read with interest the article by Abraham and Krasnodembskaya regarding mesenchymal stem cells (MSCs)‐derived extracellular vesicles for the treatment of acute respiratory distress syndrome (ARDS).1 Since December 2019, the outbreak of coronavirus disease 2019 (COVID‐19) in Wuhan, China, has drawn worldwide attention. As of February 26, 2020, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) had infected more than 82 000 people and had led to 2800 deaths from acute lung injury (ALI) and ARDS worldwide. Unfortunately, the numbers of both infected patients and fatalities are still growing and no effective drugs are clinically approved.

Similar to two other lethal coronaviruses, SARS‐CoV and MERS‐CoV, SARS‐CoV‐2 induces excessive and aberrant host immune responses that are always accompanied by cytokine storms (CS) and subsequent ALI or even ARDS, resulting in multiple organ failure and death.2 Even in patients who were treated in intensive care units for CS, persistent inflammation led to serious sequelae of lung fibrosis, causing lung dysfunction and reduced quality of life.3 Although corticosteroid given to reverse catabolism in critical illness decreased the mortality after SARS and MERS infection, the clinical application of corticosteroid has been restricted in COVID‐19, considering its delay in virus clearance and complications in survivors. There is an urgent need for advancing therapeutic interventions with both functions for CS suppression and lung reparation in critical patients.

MSCs have been found to be capable of modulating immune responses, thereby reducing inflammation as well as immunopathology and protecting alveolar epithelial cells during ALI and ARDS.4, 5, 6, 7 More importantly, MSCs were efficacious in reducing the nonproductive inflammation and in promoting lung generation in a phase 2 clinical trial (NCT03608592), as well as in patients with ALI and ARDS in clinical practice.8, 9, 10 As a result, MSCs may alleviate the SARS‐CoV‐2‐derived CS and ARDS, and have a potential effect on the treatment of subsequent chronic respiratory dysfunction and lung fibrosis.

To alleviate acute respiratory disease and reverse pulmonary fibrosis in intensive‐care SARS‐CoV‐2‐infected patients, three curative properties of MSCs have emerged (Figure 1): (a) directly inducing the apoptosis of activated T cells to relieve the aberrant and excessive immune responses, (b) homing toward specific injuries of lung to maintain homeostasis as well as promote regeneration, and (c) releasing cytokines to diminish inflammation and extracellular vesicles (EVs) to stimulate tissue reparation.1 Notably, it has been proved that MSC‐released cytokines can potently inhibit neutrophil intravasation and enhance the differentiation of macrophages.5, 6 Moreover, these MSC‐released EVs can deliver microRNA, mRNA, DNA, proteins, and metabolites into host cells in specific injuries of the lung to promote lung repair as well as regeneration and restore lung function.1

Potential mechanism of MSCs in the treatment of severe COVID‐19
FIGURE 1
Potential mechanism of MSCs in the treatment of severe COVID‐19

As the continuing epidemic threat of SARS‐CoV‐2 to global health and the fast‐growing number of fatalities, advancing new therapeutic development becomes central or primary to minimize the death and sequelae from SARS‐CoV‐2 infection. Thus, MSCs should be considered as a potential treatment for these critical patients. A recent clinical trial (NCT04252118) is expected to verify its efficacy and safety.

CONFLICT OF INTEREST

The authors declared no potential conflicts of interest.

REFERENCES

1 

AbrahamA, KrasnodembskayaA. . Mesenchymal stem cell‐derived extracellular vesicles for the treatment of acute respiratory distress syndrome. Stem Cells Transl Med. 2020;9:, pp.28‐38.

2 

HuangC, WangY, LiX, et al. . Clinical features of patients infected with 2019 novel coronavirus in Wuhan China. Lancet. 2020;395:, pp.497‐506.

3 

XieL, LiuY, FanB, et al. . Dynamic changes of serum SARS‐coronavirus IgG, pulmonary function and radiography in patients recovering from SARS after hospital discharge. Respir Res. 2005;6:, pp.5.

4 

UccelliA, PistoiaV, MorettaL. . Mesenchymal stem cells: a new strategy for immunosuppression?Trends Immunol. 2007;28:, pp.219‐226.

5 

XuAL, RodriguezLA, WalkerKP, et al. . Mesenchymal stem cells reconditioned in their own serum exhibit augmented therapeutic properties in the setting of acute respiratory distress syndrome. Stem Cells Transl Med. 2019;8:, pp.1092‐1106.

6 

MorrisonTJ, JacksonMV, CunninghamEK, et al. . Mesenchymal stromal cells modulate macrophages in clinically relevant lung injury models by extracellular vesicle mitochondrial transfer. Am J Respir Crit Care Med. 2017;196:, pp.1275‐1286.

7 

JohnsonCL, SoederY, DahlkeMH. . Concise review: mesenchymal stromal cell‐based approaches for the treatment of acute respiratory distress and sepsis syndromes. Stem Cells Transl Med. 2017;6(4):, pp.1141‐1151.

8 

MatthayMA, CalfeeCS, ZhuoH, et al. . Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): a randomised phase 2a safety trial. Lancet Respir Med. 2019;7:, pp.154‐162.

9 

LoyH, KuokDIT, HuiKPY, et al. . Therapeutic implications of human umbilical cord mesenchymal stromal cells in attenuating influenza a (H5N1) virus‐associated acute lung injury. J Infect Dis. 2019;219:, pp.186‐196.

10 

SimonsonOE, MougiakakosD, HeldringN, et al. . In vivo effects of mesenchymal stromal cells in two patients with severe acute respiratory distress syndrome. Stem Cells Transl Med. 2015;4:, pp.1199‐1213.

https://www.researchpad.co/tools/openurl?pubtype=article&doi=10.1002/sctm.20-0083&title=Mesenchymal stem cells as a potential treatment for critically ill patients with coronavirus disease 2019&author=Fanpu Ji,Liya Li,Zongfang Li,Yan Jin,Wenjia Liu,&keyword=&subject=Letters to the Editor,Letters to the Editor,