Human Umbilical Cord-Derived Mesenchymal Stem Cells for Acute Respiratory Distress Syndrome

Abstract

Objectives: To investigate the safety, feasibility, and possible adverse events of single-dose human umbilical cord-derived mesenchymal stem cells in patients with moderate-to-severe acute respiratory distress syndrome. Design: Prospective phase I clinical trial. Setting: Medical center in Kaohsiung, Taiwan. Patients: Moderate-to-severe acute respiratory distress syndrome with a Pao 2/Fio 2 ratio less than 200. Interventions: Scaling for doses was required by Taiwan Food and Drug Administration as follows: the first three patients received low-dose human umbilical cord-derived mesenchymal stem cells (1.0 × 106 cells/kg), the next three patients with intermediate dose (5.0 × 106 cells/kg), and the final three patients with high dose (1.0 × 107 cells/kg) between December 2017 and August 2019. Measurements and Main Results: Nine consecutive patients were enrolled into the study. In-hospital mortality was 33.3% (3/9), including two with recurrent septic shock and one with ventilator-induced severe pneumomediastinum and subcutaneous emphysema. No serious prespecified cell infusion-associated or treatment-related adverse events was identified in any patient. Serial flow-cytometric analyses of circulating inflammatory biomarkers (CD14+CD33+/CD11b+CD16+/CD16+MPO+/CD11b+MPO+/CD14dimCD33+) and mesenchymal stem cell markers (CD26+CD45–/CD29+CD45–/CD34+CD45–/CD44+CD45–/CD73+CD45–/CD90+CD45–/CD105+CD45–/CD26+CD45–) were notably progressively reduced (p for trend < 0.001), whereas the immune cell markers (Helper-T-cellCD3+CD4+/Cytotoxity-T-cellCD3+CD8+/Regulatory-T-cellCD4+CD25+FOXp3+) were notably increased (p for trend < 0.001) after cell infusion. Conclusions: The result of this phase I clinical trial showed that a single-dose IV infusion of human umbilical cord-derived mesenchymal stem cells was safe with favorable outcome in nine acute respiratory distress syndrome patients.

Cell-based therapy to reduce mortality from COVID-19: Systematic review and meta-analysis of human studies on acute respiratory distress syndrome

“…27 The average age of study participants was 51 to 67 years for the MSC groups and 55 to 70 years for the control groups in the comparative studies. Baseline PaO 2 /FiO 2 was in a range of 100 to 200 in six studies [21][22][23][24][25]27 and not reported in two studies in which all patients were on ventilator or extracorporeal membrane oxygenation (ECMO) support. 26,28 Baseline Acute Physiology and Chronic Health Evaluation (APACHE) scores were between 23 and 27 in one study, 22 averaged 108 in one study, 21 and 104 in the MSC group vs 89 in the control group in one study 24 (Table 1).…”

“…The studies were from six countries and regions, including China (n = 3), 20,22,26 the United States (n = 2), 21,24 United States/United Kingdom (n = 1), 23 Sweden (n = 1), 28 Taiwan (n = 1), 25 and South Korea (n = 1). 27 The average age of study participants was 51 to 67 years for the MSC groups and 55 to 70 years for the control groups in the comparative studies.…”

“…MSCs in one study, 25 and umbilical cord blood MSCs in one study. 27 One study did not report the tissue origin of the MSCs and described their cell-product as commercially obtained 20 ( Table 2).…”

“…MSCs from one donor were used in five studies, 22,24,[26][27][28] from three donors in one study, 24 and not specified in three studies. 20,23,25 Characterization of MSCs was reported in four studies, with most of the following markers: positive for CD29, CD44, CD73, CD90, CD105, CD166, HLA-ABC, and negative for CD31, CD34, CD45, CD14, and HLA-DR. 22,24,25,28 Viability was reported to be 50% to 95% (Table 2). 21,24,28 In addition, MSCs were found to be ACE2-or MSCs were administered intratracheally (n = 1), 27 intravenously (n = 115), or through a central venous catheter (n = 1).…”

“…21,24,28 In addition, MSCs were found to be ACE2-or MSCs were administered intratracheally (n = 1), 27 intravenously (n = 115), or through a central venous catheter (n = 1). [20][21][22][23][24][25][26]28 MSC infusion frequency ranged from a single administration in eight studies [20][21][22][23][24][25]27,28 to 3 to 4 administrations in one study. 26 Dosing of the stem cells ranged from 1 to 10 million cells per kilogram of body weight or a uniform dose of 300 or 900 million cells.…”