lancet-header

Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com.

Effectiveness and Safety of MSC Cell Therapies for Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis

36 Pages Posted: 16 Sep 2021

See all articles by Wenchun Qu

Wenchun Qu

Mayo Clinic - Florida - Department of Pain Medicine

Zhen Wang

Mayo Clinic - Evidence-Based Practice Center

Erica Engelberg-Cook

Mayo Clinic - Florida - Department of Neuroscience

Abu Bakar Siddik

Mayo Clinic - Florida - Department of Pain Medicine

Guojun Bu

Mayo Clinic - Florida - Center for Regenerative Medicine

Julie G. Allickson

Mayo Clinic - Center for Regenerative Medicine

Eva Kubrova

Mayo Clinic - Department of Physical Medicine and Rehabilitation

Arnold I. Caplan

Case Western Reserve University - Skeletal Research Center

Joshua M. Hare

University of Miami - Interdisciplinary Stem Cell Institute

Camillo Ricordi

University of Miami - Department of Surgery

Carl J. Pepine

University of Florida - Center for Regenerative Medicine

Joanne Kurtzberg

Duke University - Marcus Center for Cellular Cures

Jorge M. Pascual

Mayo Clinic - Division of Pulmonary, Allergy and Sleep Medicine

Jorge M. Mallea

Mayo Clinic - Division of Pulmonary, Allergy and Sleep Medicine

Ricardo L. Rodriguez

American Society Plastic Surgeons - Regenerative Medicine Committee

Tarek Nayfeh

Mayo Clinic - Evidence-Based Practice Center

Samer Saadi

Mayo Clinic - Evidence-Based Practice Center

Elaine M. Richards

University of Florida, College of Medicine, Department of Physiology and Functional Genomics

Keith March

University of Florida - Center for Regenerative Medicine

Fred P. Sanfilippo

Emory University - Department of Health Policy and Management

More...

Abstract

Background: Covid-19 has contributed to high mortality and morbidity among hospitalized patients. One of the main pathophysiological processes of the disease is an exuberant immune response leading to respiratory failure. MSC (a.k.a. mesenchymal stem cell or medicinal signaling cell) cell therapies have shown promise in modulating responses in inflammatory diseases and trend in decreasing mortality in ARDS. Controlled clinical trials with limited sample size assessing the effectiveness of MSC in patients hospitalized for COVID-19 suggest safety and potential to improve outcomes.  We performed a meta-analysis of published trials assessing the clinical effectiveness and adverse events of MSC cell therapy in individuals hospitalized for COVID-19.

Methods: Systematic searches were performed in multiple databases through April 8 th , 2021. Reports in all languages were included. Randomized clinical trials, comparative observational studies, and case series/case reports that evaluated safety and/or efficacy of MSC cell therapy in hospitalized patients with COVID-19.Independent reviewers selected studies and extracted data. Random effects model was used to pool outcomes from RCTs and comparative observational studies. Outcome measures included all-cause mortality, serious adverse events (SAEs), mild adverse events (AEs), pulmonary function, laboratory and imaging findings. 

Findings: A total of 413 patients were identified from 25 studies, which included 8 controlled trials (3 RCTs), 5 comparative observational studies, n=300) and 17 case-series/case reports (n=113). The patients age was 60.5 years (mean) and 33.7% were women. When compared with the control group receiving institutionally defined standard of care, MSC cell therapy was associated with reduction in all-cause mortality (RR=0.31, 95% CI: 0.12 to 0.75, I 2 =0.0%; 3 RCTs and 5 comparative observational studies, 300 patients), and reduction in SAEs (IRR=0.36, 95% CI: 0.14 to 0.90, I 2 =0.0%; 3 RCTs and 2 comparative studies, n=219). There was no significant difference in AE rate. A sub-group with pulmonary function studies suggested improvement in patients receiving MSC cell therapy. 

Interpretation: Together these findings support the potential for MSC cell therapy to decrease all-cause mortality, reduce SAEs, and improve pulmonary function in patients hospitalized for COVID-19 compared to conventional care. Large scale double-blinded, well-powered randomized controlled trials should be conducted to further explore these results. 

Funding: None to declare.

Declaration of Interest: W. Q., J. M. H., J. K., C. R. reported roles as principal investigators of MSC trials. J. M. H. reported having a patent for cardiac cell-based therapy, holds equity in Vestion, Inc., and maintains a professional relationship with Vestion, Inc. as a consultant and member of the Board of Directors and Scientific Advisory Board; J. M. H. is also the Chief Scientific Officer, a compensated consultant and advisory board member, for Longeveron and holds equity in Longeveron; J. M. H. is the coinventor of intellectual property licensed to Longeveron. J. M. H. declared inventor or patent holder and research funding from Longeveron, Heart Genomics; advisory role and research funding with Vestion; research funding from NHLBI. J. K. declare Intellectual property rights with IDF, hCT-MSC for treatment of ASD, HIE, which were licensed to CryoCell Int’l by Duke University; NMDP Scientific Advisor; Celularity SAB; research funding from the Marcus Foundation, NIH, HRSA; leadership position with Istari—CMO (spouse). G. B. consults for SciNeuro and Vida Ventures, had consulted for AbbVie, E-Scape, and Eisai, and receives funding from NIH and Cure Alzheimer’s Fund. He serves as a Co-Editor-in-Chief for Molecular Neurodegeneration. The other authors indicated no potential conflicts of interest. K.M. is a consultant in RESTEM.

Keywords: MSC, COVID, Cytokine storm, Pulmonary, Hospital recovery

Suggested Citation

Qu, Wenchun and Wang, Zhen and Engelberg-Cook, Erica and Bakar Siddik, Abu and Bu, Guojun and Allickson, Julie G. and Kubrova, Eva and Caplan, Arnold I. and Hare, Joshua M. and Ricordi, Camillo and Pepine, Carl J. and Kurtzberg, Joanne and Pascual, Jorge M. and Mallea, Jorge M. and Rodriguez, Ricardo L. and Nayfeh, Tarek and Saadi, Samer and Richards, Elaine M. and March, Keith and Sanfilippo, Fred P., Effectiveness and Safety of MSC Cell Therapies for Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis. Available at SSRN: https://ssrn.com/abstract=3924851 or http://dx.doi.org/10.2139/ssrn.3924851

Wenchun Qu (Contact Author)

Mayo Clinic - Florida - Department of Pain Medicine

Jacksonville, FL
United States

Zhen Wang

Mayo Clinic - Evidence-Based Practice Center

Rochester, MN
United States

Erica Engelberg-Cook

Mayo Clinic - Florida - Department of Neuroscience ( email )

4500 San Pablo Rd S
Jacksonville, FL 32224
United States

Abu Bakar Siddik

Mayo Clinic - Florida - Department of Pain Medicine ( email )

Jacksonville, FL
United States

Guojun Bu

Mayo Clinic - Florida - Center for Regenerative Medicine ( email )

Jacksonville, FL
United States

Julie G. Allickson

Mayo Clinic - Center for Regenerative Medicine ( email )

Rochester, MN
United States

Eva Kubrova

Mayo Clinic - Department of Physical Medicine and Rehabilitation ( email )

Rochester, MN
United States

Arnold I. Caplan

Case Western Reserve University - Skeletal Research Center ( email )

Cleveland, OH
United States

Joshua M. Hare

University of Miami - Interdisciplinary Stem Cell Institute

United States

Camillo Ricordi

University of Miami - Department of Surgery

United States

Carl J. Pepine

University of Florida - Center for Regenerative Medicine ( email )

Gainesville, FL
United States

Joanne Kurtzberg

Duke University - Marcus Center for Cellular Cures ( email )

United States

Jorge M. Pascual

Mayo Clinic - Division of Pulmonary, Allergy and Sleep Medicine ( email )

Jacksonville, FL
United States

Jorge M. Mallea

Mayo Clinic - Division of Pulmonary, Allergy and Sleep Medicine ( email )

Jacksonville, FL
United States

Ricardo L. Rodriguez

American Society Plastic Surgeons - Regenerative Medicine Committee ( email )

United States

Tarek Nayfeh

Mayo Clinic - Evidence-Based Practice Center ( email )

Rochester, MN
United States

Samer Saadi

Mayo Clinic - Evidence-Based Practice Center ( email )

Rochester, MN
United States

Elaine M. Richards

University of Florida, College of Medicine, Department of Physiology and Functional Genomics ( email )

1600 SW Archer Rd
M509
Gainesville, FL 32610
United States

Keith March

University of Florida - Center for Regenerative Medicine ( email )

Gainesville, FL
United States

Fred P. Sanfilippo

Emory University - Department of Health Policy and Management ( email )

Atlanta, GA
United States

Click here to go to TheLancet.com

Paper statistics

Downloads
55
Abstract Views
451
PlumX Metrics