Are Stem Cells a Solution to COVID-19 Crisis?
MSCs could be the most promising candidate for the treatment of SARS-CoV-2 infections (Table 1). Since the key for the treatment of SARS-CoV-2 infection lies in the management of the cytokine storm in the lungs, MSCs are well-suited considering their main mechanism of action is through their immunomodulatory and anti-inflammatory properties (Fatima et al., 2017). The safety profile and efficacy of MSCs are well-established based on the results from a number of completed clinical studies investigating the therapeutic potential of these therapies in lung diseases such as ARDS (Matthay et al., 2019; Chen J. et al., 2020) and bronchopulmonary dysplasia (Namba, 2019), cardiovascular diseases (Kim et al., 2015; Suvakov et al., 2020), diabetes (Thakkar et al., 2015; Cho et al., 2018), and spinal cord injury (Xu and Yang, 2019).
Table 1  Selected clinical studies using stem cells for the treatment of SARS-CoV-2 infection.
Cell type   Dosage   Number of patients   Outcome   Stage of study   Reference or NCT numbers#
MSCs (tissue source unspecified)  Single dose of 1 × 106 cells per kg, IV  7 patients with severe COVID-19 pneumonia  Regulation of inflammatory response (Decreased plasma C-reaction protein, reduced cytokine-secreting immune cells, reduced TNF-α, increased IL-10 and VEGF)  Complete  Leng et al., 2020
Adipose tissue-derived MSCs  Two serial doses of 1.5 × 106 cells per kg, IV  Estimated: 100 patients  N/A  Phase 2; Not yet recruiting  NCT04348461
Dental pulp stem cells  3 × 107 cells IV on day 1, 4, and 7  Estimated: 20 patients  N/A  Phase 1 clinical trial; recruiting  NCT04336254
Dental pulp stem cells  1 × 106 cells per kg IV on day 1, 3, and 7  Estimated: 24 patients  N/A  Early Phase 1; Not yet recruiting  NCT04302519
Wharton's Jelly MSCs  3 doses of 1 × 106 cells per kg IV, 3 days apart from each other  Estimated: 5 patients  N/A  Phase 1 clinical trial; recruiting  NCT04313322
MSCs (tissue source unspecified)  3 × 107 cells IV on day 0, 3, and 6  Estimated: 20 patients  N/A  Phase 1 clinical trial; recruiting  NCT04252118
Umbilical cord MSCs  9.9 × 107 cells IV on day 1, 3, 5, and 7  Estimated: 10 patients  N/A  Phase 2 clinical trial; recruiting  NCT04269525
Umbilical cord MSCs  0.5 × 106 cells per kg body weight IV on day 1, 3, 5, and 7  Estimated: 48 patients  N/A  Not yet recruiting  NCT04273646
Bone Marrow MSCs  Single dose of 1 × 106 cells per kg, IV  Estimated: 20 patients  N/A  Phase 1 clinical trial; Not yet recruiting  NCT04346368
Human embryonic stem cells derived matrix-regulatory cells  3 cohorts who receive doses of 3, 5, or 10 million cells per kg body weight IV  Estimated: 9 patients  N/A  Phase 1 clinical trial; recruiting  NCT04331613
#  NCT numbers refer to ClinicalTrials.gov Identifier numbers. Other types of stem cells investigated for potential treatment of SARS-CoV-2 infections include genetically engineered human induced pluripotent stem cells (iPSC). A recent study presented a deleterious effect on the cells in vitro when iPSCs were exposed to SARS-CoV-2, where the pluripotency of iPSCs was lost leading to fibroblast-like phenotype (Zebin et al., 2020). Therefore, evidence-based selection of stem cell type for the treatment of COVID-19 is critical for safety and efficacy.