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Human umbilical cord-derived mesenchymal stem cell therapy in patients. . .
Meng et al.
7
Statistical analysis cells): implications for therapeutic use. Bone Marrow Transplant. 16,557–564
The clinical and laboratory variables were summarized using (1995).
descriptive statistics and confidence intervals. The χ² test or 10. Chuang, H. M. et al. Mesenchymal stem cell therapy of pulmonary fibrosis:
Fisher’s exact test was used to analyze categorical data, while the improvement with target combination. Cell Transplant. 27, 1581–1587 (2018).
11. Ball, L. M. et al. Multiple infusions of mesenchymal stromal cells induce sustained
Mann–Whitney U test was used to compare the difference
remission in children with steroid-refractory, grade III-IV acute graft-versus-host
between the two groups. A P value of <0.05 was considered
disease. Br. J. Haematol. 163, 501–509 (2013).
statistically significant.
12. Wilson, J. G. et al. Mesenchymal stem (stromal) cells for treatment of ARDS: a
phase 1 clinical trial. Lancet Respir. Med. 3,24–32 (2015).
13. Matthay, M. A. et al. Treatment with allogeneic mesenchymal stromal cells for
DATA AVAILABILITY moderate to severe acute respiratory distress syndrome (START study): a ran-
All of the data generated and analyzed during this study are included in our domised phase 2a safety trial. Lancet Respir. Med. 7, 154–162 (2019).
manuscript. 14. Zumla, A. et al. Reducing mortality and morbidity in patients with severe COVID-
19 disease by advancing ongoing trials of mesenchymal stromal (stem) cell (MSC)
therapy -achieving global consensus and visibility for cellular host-directed
ACKNOWLEDGEMENTS therapies. Int. J. Infect. Dis. 17, 431–439 (2020).
15. Zhang, Y. et al. Analysis of serum cytokines in patients with severe acute
This work was supported by The National Key R&D Program of China
respiratory syndrome. Infect. Immun. 72, 4410–4415 (2004).
(2020YFC0841900, 2020YFC0844000), The Innovation Groups of the National Natural
16. Mangalmurti, N. & Hunter, C. A. Cytokine storms: understanding COVID-19.
Science Foundation of China (81721002), The National Science and Technology Major
Immunity 28, 30272–30277 (2020).
Project (2017YFA0105703), The Military Emergency Research Project for COVID-19
17. Chen, B. et al. Overview of lethal human coronaviruses. Signal. Transduct. Target.
(BWS20J006), and The Project for Innovation of Military Medicine of China
Ther. 5, 89 (2020).
(16CXZ045). Sir Zumla is co-PI of the Pan-African Network on Emerging and Re-
18. Lohan, P. et al. Anti-donor immune responses elicited by allogeneic mesenchy-
Emerging Infections (PANDORA-ID-NET – https://www.pandora-id.net/) awarded by
mal stem cells and their extracellular vesicles: are we still learning? Front.
the European and Developing Countries Clinical Trials Partnership. Z.A. is in receipt of
a National Institutes of Health Research senior investigator award. W.F.S., Z.C., M.M., Immunol. 8, 1626 (2017).
19. Thompson, M. et al. Cell therapy with intravascular administration of mesench-
and Z.A. are founder members of the Global Cancer and Infectious Diseases
ymal stromal cells continues to appear safe: an updated systematic review and
consortium for Host-directed therapies: Weblink: https://www.fchampalimaud.org/
meta-analysis. EClinicalMedicine 19, 100249 (2020).
covid19/aci/.
20. Zheng, G. et al. Treatment of aute respiratory distress syndrome with allogeneic
adipose-derived mesenchymal stem cells: a randomized, placebo-controlled pilot
study. Respir. Res. 15, 39 (2014).
AUTHOR CONTRIBUTIONS
21. Leng, Z. et al. Transplantation of ACE2 mesenchymal stem cells improves the
All authors made substantial contributions to this work. W.F.S. proposed initial idea
outcome of patients with COVID-19 pneumonia. Aging Dis. 11, 216–228 (2020).
and study design. M.F., X.R., W.S., and X.Z. further co-designed the study protocol. M.
22. Zhang, Z. et al. Safety and immunological responses to human mesenchymal stem
F., X.Z., S.L., H.L., Y.T., Z.D., Z.P., J.T., L.Y., and L.L. took care of the patients and
cell therapy in difficult-to-treat HIV-1-infected patients. AIDS 27,1283–1293 (2013).
performed the follow-up checks. M.F., X. R., Z.J, Z.C., Y.X., and S.M. collected and
23. Shi, M. et al. Human mesenchymal stem cell transfusion is safe and improves liver
analyzed the data. X.R., Z.J., F.X., S.J., and Z.C. performed immunological assays. W.F.S.,
function in acute-on-chronic liver failure patients. Stem Cells Transl. Med. 1,
X.R., Z.A., and M.M. co-wrote the manuscript, including the figures and tables. All of
725–731 (2012).
the authors have read the paper and approved the final version submitted for
24. Dienz, O. et al. Essential role of IL-6 in protection against H1N1 influenza virus by
publication.
promoting neutrophil survival in the lung. Mucosal Immunol. 5, 258–266 (2012).
25. Huang, C. et al. Clinical features of patients infected with 2019 novel coronavirus
in Wuhan, China. Lancet 395, 497–506 (2020).
ADDITIONAL INFORMATION 26. Fan, H. et al. Pre-treatment with IL-1β enhances the efficacy of MSC transplan-
The online version of this article (https://doi.org/10.1038/s41392-020-00286-5) tation in DSS-induced colitis. Cell. Mol. Immunol. 9, 473–481 (2012).
contains supplementary material, which is available to authorized users. 27. Giamarellos-Bourboulis, E. J. et al. Complex immune dysregulation in COVID-19
patients with severe respiratory failure. Cell Host Microbe 27, 992–1000 (2020).
28. Wang, L. et al. Clinical observation of employment of umbilical cord derived
Competing interests: The authors declare no competing interests. mesenchymal stem cell for juvenile idiopathic arthritis therapy. Stem Cells Int.
2016, 9165267 (2016).
29. Dominici, M. et al. Minimal criteria for defining multipotent mesenchymal stromal
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