Use of Multiple Doses of Intravenous Infusion of Umbilical Cord-Mesenchymal Stem Cells for the Treatment of Adult Patients with Severe COVID-19-Related Acute Respiratory Distress Syndrome: Literature Review

Po-Ren Hsueh; Sung-Jung Ho; Po-Chuen Hsieh; I-Min Liu; Shio-Shin Jean

doi:10.1155/2023/7179592

Use of Multiple Doses of Intravenous Infusion of Umbilical Cord-Mesenchymal Stem Cells for the Treatment of Adult Patients with Severe COVID-19-Related Acute Respiratory Distress Syndrome: Literature Review

Stem Cells Int. 2023 Aug 18:2023:7179592. doi: 10.1155/2023/7179592. eCollection 2023.

Authors

Po-Ren Hsueh^{1

2

3}, Sung-Jung Ho⁴, Po-Chuen Hsieh⁵, I-Min Liu⁵, Shio-Shin Jean^{5

6}

Affiliations

¹ Departments of Laboratory Medicine and Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan.
² School of Medicine, China Medical University, Taichung, Taiwan.
³ Departments of Laboratory Medicine and Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
⁴ Division of Pulmonary Medicine, Department of Internal Medicine, Min-Sheng General Hospital, Taoyuan, Taiwan.
⁵ Department of Pharmacy, College of Pharmacy and Health Care, Tajen University, Pingtung, Taiwan.
⁶ Departments of Internal Medicine and Critical Care Medicine, Min-Sheng General Hospital, Taoyuan, Taiwan.

Abstract

Objectives: Acute respiratory distress syndrome (ARDS) is a critical complication in severe COVID-19 patients. The intravenous infusion (IVF) of umbilical cord- (UC-) mesenchymal stem cells (MSCs), validated to substantially reduce the release of several inflammatory cytokines in vivo, was also shown to exhibit benefits in improving hypoxemia among severe COVID-19 patients. A single dose of IVF-UC-MSCs therapy for severe COVID-19 patients was shown to alleviate the initial ARDS severity, but have 50%-67% case-fatality rates. In Taiwan, few adult patients with severe COVID-19-induced ARDS receiving compassionate adjuvant treatment consisting of either a single dose (1-10 × 10⁶ cells/kg body weight (kg BW)) or three doses (5 × 10⁶ cells/kg BW in each dose) of IVF-UC-MSCs had good outcomes. However, the optimal dosage and rounds of IVF-UC-MSCs administration for the treatment of severe COVID-19 patients with ARDS are undetermined.

Methods: We reviewed the 2020-2022 PubMed literature database concerning the clinical efficacy of IVF-UC-MSCs among severe COVID-19 patients.

Results: The data of COVID-19 case series in the PubMed literature revealed a notable heterogeneity in the therapeutic dosage (a single dose: 1-10 × 10⁶ cells/kg BW; and three doses: 50-200 × 10⁶ cells/kg BW in each dose) and the post-ARDS days of IVF-UC-MSCs administration (a single dose: 1-12; and multiple doses: 5-14) for the treatment of severe COVID-19-associated ARDS. The survival rates among these severe COVID-19 patients ranged from 50% to 76%. However, an overall rate of 93.1% of significant improvement in hypoxemia was observed for the COVID-19 survivors receiving IVF-UC-MSCs at the initial ARDS stage.

Conclusions: According to our analysis, the ideal treatment dosage of IVF-UC-MSCs for severe COVID-19-induced ARDS is likely 5 × 10⁶ cells/kg BW for three cycles within 5 days of ARDS onset in severe COVID-19 patients.

Publication types

Review