Mesenchymal Stem Cells
Last Updated: July 17, 2020
- The COVID-19 Treatment Guidelines Panel recommends against the use of mesenchymal stem cells (MSCs) for the treatment of COVID-19, except in a clinical trial (AII).
Rationale for Recommendation
MSCs are investigational products that have been studied extensively for broad clinical applications in regenerative medicine1 and for their immunomodulatory properties.2 No MSCs are approved by the Food and Drug Administration (FDA) for the treatment of COVID-19. There are insufficient data to assess use of MSCs for the treatment of COVID-19.
The FDA has recently issued several warnings about patients being potentially vulnerable to stem cell treatments that are illegal and potentially harmful.3 Several cord blood-derived products are currently licensed by the FDA for indications such as the treatment of cancer (e.g., stem cell transplant) or rare genetic diseases, and as scaffolding for cartilage defects and wound beds. None of these products are approved for the treatment of COVID-19 or any other viral disease.4 In the United States, MSCs should not be used for the treatment of COVID-19 outside of an FDA-approved clinical trial, expanded access programs, or an Emergency Investigational New Drug application (AII).
Rationale for Use in COVID-19
MSCs are multipotent adult stem cells that are present in most human tissues, including the umbilical cord. MSCs can self-renew by dividing and can differentiate into multiple types of tissues, including osteoblasts, chondroblasts, adipocytes, hepatocytes, and others, which has led to a robust clinical research agenda in regenerative medicine. It is hypothesized that MSCs could reduce the acute lung injury and inhibit the cell-mediated inflammatory response induced by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). Furthermore, MSCs lack the angiotensin-converting enzyme 2 receptor that SARS-COV-2 uses for viral entry into cells; therefore, MSCs are resistant to infection.5,6
Data supporting the use of MSCs in patients with viral infections, including COVID-19, are limited to case reports and small, open-label studies.
Clinical Data for COVID-19
- A pilot study of intravenous MSC transplantation in China enrolled 10 patients with confirmed COVID-19 categorized according to the National Health Commission of China criteria as critical, severe, or common type. Seven patients (one with critical illness, four with severe illness, and two with common-type illness) received MSCs; three patients with severe illness received placebo. All seven patients who received MSCs recovered. Among the three severely ill control patients, one died, one developed acute respiratory distress syndrome (ARDS), and one remained stable with severe disease.7
Clinical Data for Other Viral Infections
- In an open-label study of MSCs for the treatment of H7N9 influenza in China, 17 patients received MSC treatment plus standard of care, and 44 patients received standard of care only. In the MSC group, three patients (17.6%) died; in the control group, 24 patients (54.5%) died. The 5-year follow-up was limited to five patients in the MSC group. No safety concerns were identified.8
See ClinicalTrials.gov for a list of clinical trials evaluating MSCs for the treatment of COVID-19 and COVID-19-related ARDS that are underway and recruiting participants.
Risks associated with MSC transfusion appear to be uncommon. The potential risks include failure of the cells to work as expected, potential for MSCs to multiply or change into inappropriate cell types, product contamination, growth of tumors, infections, thrombus formation, and administration site reactions.9
Considerations in Pregnancy
There are insufficient data to assess the risk of MSC use during pregnancy.
Considerations in Children
There are insufficient data on the efficacy and safety of MSC use in children.
- Samsonraj RM, Raghunath M, Nurcombe V, Hui JH, van Wijnen AJ, Cool SM. Concise review: multifaceted characterization of human mesenchymal stem cells for use in regenerative medicine. Stem Cells Transl Med. 2017;6(12):2173-2185. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29076267.
- Li N, Hua J. Interactions between mesenchymal stem cells and the immune system. Cell Mol Life Sci. 2017;74(13):2345-2360. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28214990.
- Food and Drug Administration. FDA warns about stem cell therapies. 2019. Available at: https://www.fda.gov/consumers/consumer-updates/fda-warns-about-stem-cell-therapies. Accessed July 2, 2020.
- Food and Drug Administration. Approved cellular and gene therapy products. 2019. Available at: https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-products. Accessed July 2, 2020.
- Lukomska B, Stanaszek L, Zuba-Surma E, Legosz P, Sarzynska S, Drela K. Challenges and controversies in human mesenchymal stem cell therapy. Stem Cells Int. 2019:9628536. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31093291.
- Shetty AK. Mesenchymal stem cell infusion shows promise for combating coronavirus (COVID-19)- induced pneumonia. Aging Dis. 2020;11(2):462-464. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32257554.
- Leng Z, Zhu R, Hou W, et al. Transplantation of ACE2- mesenchymal stem cells improves the outcome of patients with COVID-19 pneumonia. Aging Dis. 2020;11(2):216-228. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32257537.
- Chen J, Hu C, Chen L, et al. Clinical study of mesenchymal stem cell treating acute respiratory distress syndrome induced by epidemic influenza A (H7N9) infection, a hint for COVID-19 treatment. Engineering (Beijing). 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32292627.
- Centers for Disease Control and Prevention. Stem cell and exosome products. 2019. Available at: https://www.cdc.gov/hai/outbreaks/stem-cell-products.html. Accessed July 2, 2020.