Review of Trials Currently Testing Stem Cells for Treatment of Respiratory Diseases: Facts Known to Date and Possible Applications to COVID-19

Abstract

Therapeutic clinical and preclinical studies using cultured cells are on the rise, especially now that the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) a "public health emergency of international concern", in January, 2020. Thus, this study aims to review the outcomes of ongoing clinical studies on stem cells in Severe Acute Respiratory Syndrome (SARS), Acute Respiratory Distress Syndrome (ARDS), and Middle East Respiratory Syndrome (MERS). The results will be associated with possible applications to COVID-19. Only three clinical trials related to stem cells are considered complete, whereby two are in Phase 1 and one is in Phase 2. Basically, the ongoing studies on coronavirus are using mesenchymal stem cells (MSCs) derived from bone marrow or the umbilical cord to demonstrate their feasibility, safety, and tolerability. The studies not related to coronavirus are all in ARDS conditions; four of them are in Phase 1 and three in Phase 2. With the COVID-19 boom, many clinical trials are being carried out using different sources with an emphasis on MSC-based therapy used to inhibit inflammation. One of the biggest challenges in the current treatment of COVID-19 is the cytokine storm, however MSCs can prevent or mitigate this cytokine storm through their immunomodulatory capacity. We look forward to the results of the ongoing clinical trials to find a treatment for the disease. Researchers around the world are joining forces to help fight COVID-19. Stem cells used in the current clinical studies are a new therapeutic promise for COVID-19 where pharmacological treatments seem insufficient.

Renal Involvement in Patients with COVID-19 Pneumonia and Outcomes After Stem Cell Nebulization

“…It is well known that stem cells have the potential to differentiate into lung cells among others, reprogramming the immune response to reduce destructive inflammatory elements and directly replace damaged cells and tissues. (9) Furthermore, the growth factor cocktail has apocrine effects on the modulation of the cytokine storm, not only in the lungs but throughout the circulatory system, explaining this phenomenon found in our study, which was evidenced by a decrease in acute phase reactants. It is almost certain that if we had the chance to treat those patients earlier, we would be able to avoid the AKI and hemodialysis requirement, since the immunomodulation with the therapy would suppress the cytokine storm.…”

“…The lower incidence of sepsis in group A can be explained by this phenomenon, since the shorter hospital stay is a protective factor against nosocomial infections,(23) and it was found that around 3 patients are required to be treated to have this protective effect with the stem cell nebulization (NNT=2.5). An attenuation of bacterial sepsis mediated by stem cells had been described, via several mechanisms, such as improving the phagocytic ability, secreting anti-microbial peptides,(9,24) and increasing bacterial clearance. (9,25)…”

“…An attenuation of bacterial sepsis mediated by stem cells had been described, via several mechanisms, such as improving the phagocytic ability, secreting anti-microbial peptides,(9,24) and increasing bacterial clearance. (9,25)…”

“…(8) Given the potential of the stem cells in sepsis and clinical evolution of chronic conditions, with the stimulation by humoral factors, strategies such as stem cell-based therapy are being proposed to regulate inflammation, prevent or mitigate this cytokine storm through their immunomodulatory capacity. (9)…”

Features and outcomes of secondary sepsis and urinary tract infections in COVID-19 patients treated with stem cell nebulization

“…Given the immunomodulatory potential of the stem cells in sepsis and clinical evolution of chronic conditions with the stimulation by humoral factors, strategies such as stem cell-based therapy are being proposed to regulate inflammation, prevent or mitigate this cytokine storm through their immunomodulatory capacity. 5…”