In order to identify approaches to manage the current Covid-19 pandemic, the therapeutic use of mesenchymal stromal cells (MSCs) is increasingly becoming the focus of research in addition to the search for a vaccine.
MSC can be isolated from different tissues (e.g. bone marrow, fat tissue, umbilical cord) and have immunomodulatory and regenerative potential. MSC have tissue regenerating, anti-inflammatory and antifibrotic effects through the secretion and expression of different cytokines, growth factors, messengers, miRNA and surface molecules.
Resident and transplanted MSCs seem to play a central role in the pathogenesis of various viral infections (e.g. H5N1, HIV, hepatitis B) and lung diseases (e.g. acute lung injury ALI, asthma) and can significantly contribute to mild disease progression. This therapeutic approach gives hope for a successful use of MSC in the treatment of severe Covid-19 infections. Although not all aspects of the pathogenesis of Covid-19 infection are yet understood, it seems that the induction of a cytokine storm in the alveolar tissue of the lung is critical and crucial for the course of Covid-19 infection. This leads to acute respiratory distress syndrome (ARDS), systemic organ involvement and may ultimately lead to death (Rocha JLM, de Oliveira WCF, Noronha NC, et al. Mesenchymal Stromal Cells in Viral Infections: Implications for COVID-19 [published online ahead of print, 2020 Sep 7]. Stem Cell Rev Rep. 2020;1-23).
Using allogeneic MSCs, which can attenuate the cytokine storm and thus prevent a life-threatening course of the disease, would offer a beneficial treatment option not only for Covid-19 patients. The manufacturing, storage and availability of allogeneic MSC products is already well established.
Several clinical studies (https://clinicaltrials.gov) are currently ongoing to establish MSC as a therapeutic approach for SARS-CoV-2 infections (Eiro N, Cabrera JR, Fraile M, Costa L, Vizoso FJ. The Coronavirus Pandemic (SARS-CoV-2): New Problems Demand New Solutions, the Alternative of Mesenchymal (Stem) Stromal Cells. Front Cell Dev Biol. 2020;8:645).
Although the search for urgently needed Covid-19 therapies is currently a hot topic, there are also some critical voices that focus on the use of MSC for Covid-19, which primarily refer to a lack of haemocompatibility or failed up-scaling of the product. (Moll G, Drzeniek N, Kamhieh-Milz J, Geissler S, Volk HD, Reinke P. MSC Therapies for COVID-19: Importance of Patient Coagulopathy, Thromboprophylaxis, Cell Product Quality and Mode of Delivery for Treatment Safety and Efficacy. Front Immunol. 2020;11:1091)
However, as long as well-characterized, safe cell products from robust manufacturing processes are used, MSCs are currently among the most promising candidates for the treatment of pneumonia and ARDS in COVID-19 infected patients.
Author: Dr. Petra Höhn, GMP Documentation Expert, Valicare GmbH, Frankfurt/Germany
