» Articles » PMID: 32425638

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 Therapies

Abstract

As of May 17th 2020, the novel coronavirus disease 2019 (COVID-19) pandemic has caused 307,395 deaths worldwide, out of 3,917,366 cases reported to the World Health Organization. No specific treatments for reducing mortality or morbidity are yet available. Deaths from COVID-19 will continue to rise globally until effective and appropriate treatments and/or vaccines are found. In search of effective treatments, the global medical, scientific, pharma and funding communities have rapidly initiated over 500 COVID-19 clinical trials on a range of antiviral drug regimens and repurposed drugs in various combinations. A paradigm shift is underway from the current focus of drug development targeting the pathogen, to advancing cellular Host-Directed Therapies (HDTs) for tackling the aberrant host immune and inflammatory responses which underlie the pathogenesis of SARS-CoV-2 and high COVID-19 mortality rates. We focus this editorial specifically on the background to, and the rationale for, the use and evaluation of mesenchymal stromal (Stem) cells (MSCs) in treatment trials of patients with severe COVID-19 disease. Currently, the ClinicalTrials.gov and the WHO Clinical Trials Registry Platform (WHO ICTRP) report a combined 28 trials exploring the potential of MSCs or their products for treatment of COVID-19. MSCs should also be trialed for treatment of other circulating WHO priority Blueprint pathogens such as MERS-CoV which causes upto 34% mortality rates. It's about time funding agencies invested more into development MSCs per se, and also for a range of other HDTs, in combination with other therapeutic interventions. MSC therapy could turn out to be an important contribution to bringing an end to the high COVID-19 death rates and preventing long-term functional disability in those who survive disease.

Citing Articles

A comprehensive review on pharmacologic agents, immunotherapies and supportive therapeutics for COVID-19.

Sharun K, Tiwari R, Yatoo M, Natesan S, Megawati D, Singh K Narra J. 2024; 2(3):e92.

PMID: 38449903 PMC: 10914132. DOI: 10.52225/narra.v2i3.92.


Safety of multiple intravenous infusions of adipose-derived mesenchymal stem cells for hospitalized cases of COVID-19: a randomized controlled trial.

de Dios C, Vij R, Kim H, Park H, Chang D Front Med (Lausanne). 2024; 10:1321303.

PMID: 38188343 PMC: 10770855. DOI: 10.3389/fmed.2023.1321303.


Clinical Trials of Mesenchymal Stem Cells for the Treatment of COVID 19.

Zendedel E, Tayebi L, Nikbakht M, Hasanzadeh E, Asadpour S Curr Stem Cell Res Ther. 2023; 19(8):1055-1071.

PMID: 37815188 DOI: 10.2174/011574888X260032230925052240.


Systematic review and meta-analysis of cell therapy for COVID-19: global clinical trial landscape, published safety/efficacy outcomes, cell product manufacturing and clinical delivery.

Couto P, Al-Arawe N, Filgueiras I, Fonseca D, Hinterseher I, Catar R Front Immunol. 2023; 14:1200180.

PMID: 37415976 PMC: 10321603. DOI: 10.3389/fimmu.2023.1200180.


Inhibition of LPS-Induced Inflammatory Response of Oral Mesenchymal Stem Cells in the Presence of Galectin-3.

Paganelli A, Diomede F, Marconi G, Pizzicannella J, Rajan T, Trubiani O Biomedicines. 2023; 11(6).

PMID: 37371614 PMC: 10295455. DOI: 10.3390/biomedicines11061519.


References
1.
Ullah I, Subbarao R, Rho G . Human mesenchymal stem cells - current trends and future prospective. Biosci Rep. 2015; 35(2). PMC: 4413017. DOI: 10.1042/BSR20150025. View

2.
Li H, Liu L, Zhang D, Xu J, Dai H, Tang N . SARS-CoV-2 and viral sepsis: observations and hypotheses. Lancet. 2020; 395(10235):1517-1520. PMC: 7164875. DOI: 10.1016/S0140-6736(20)30920-X. View

3.
Menter T, Haslbauer J, Nienhold R, Savic S, Hopfer H, Deigendesch N . Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction. Histopathology. 2020; 77(2):198-209. PMC: 7496150. DOI: 10.1111/his.14134. View

4.
Ankrum J, Ong J, Karp J . Mesenchymal stem cells: immune evasive, not immune privileged. Nat Biotechnol. 2014; 32(3):252-60. PMC: 4320647. DOI: 10.1038/nbt.2816. View

5.
Yip H, Fang W, Li Y, Lee F, Lee C, Pei S . Human Umbilical Cord-Derived Mesenchymal Stem Cells for Acute Respiratory Distress Syndrome. Crit Care Med. 2020; 48(5):e391-e399. DOI: 10.1097/CCM.0000000000004285. View