Viruses have wreaked havoc with humankind longer than we’ve been a distinct species. With the rise and global spread of COVID-19, it becomes apparent that this has not changed. However, our species’ ability to fight viral infections has changed, and quite dramatically within the past few decades. While we have not advanced to the point that we can cure viral infections, new modalities, such as stem cell therapy, show great promise for helping treat patients, address symptoms, and even improve their quality of life.
What Does the Science Say?
Stem cells have been researched and studied for their use in tissue regeneration and to combat viruses. For instance, mesenchymal stromal cells have been used successfully in patients struggling with hepatitis B, where they have helped to regenerate tissue and improve immune system reaction to the virus.
According to a study published in Stem Cells International,
"Advances in preclinical and clinical models of transplanted MSCs strongly support the potential role of MSCs on tissue regeneration and homeostasis. The major sources of MSCs which have been widely reported in clinical trials in terms of regenerative medicine are bone marrow, adipose tissues, and umbilical cord blood; for example, autologous bone marrow MSCs (BM-MSCs) transplantation could improve the short-term efficacy for the treatment of liver failure caused by hepatitis B and also the prognosis of liver function in end-stage liver disease and MSCs derived from adipose tissues (AD-MSCs) have been proven to be safe for using as therapeutic agents for autoimmune-mediated disorders, cardiovascular diseases, and soft tissue regeneration."
How Do Stem Cells Help Fight Viral Infection?
While the role of stem cells in regeneration and fighting inflammation is well-documented in studies, their effectiveness in fighting viral infection is less clear. According to the same Stem Cells International study cited above,
"Numerous studies have shown that MSCs possess immunoregulatory properties by modulating the proliferation and function of several immune cells, for example, inhibiting differentiation of monocytes into dendritic cells (DCs), altering the cytokine profiles of DCs to result in an upregulation of regulatory cytokines and downregulation of inflammatory cytokines, inducing tolerant phenotypes of naive and effector T cells, inhibiting antibody production by B cells, and suppressing NK cell proliferation and NK cell-mediated cytotoxicity.
These immunomodulatory activities are mediated by both cell-cell interactions and secreted cytokines including interferon- (IFN-) γ, indoleamine 2,3-dioxygenase (IDO), transforming growth factor- (TGF-) β, interleukin (IL-) 6, IL-10, and prostaglandin E2. Given the immunomodulatory activity of MSCs, together with their low MHC class I expression, MSCs have been utilized to prevent and/or treat steroid-resistant graft-versus-host disease (GvHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) that have failed treatment with conventional immunosuppressant drugs. Administration of MSCs has successfully reduced the incidence and severity of GvHD and has also improved the outcomes of clinical diseases associated with aberrant immune responses."
Another study, this one published in the journal Stem Cell Research & Therapy, notes that
"Acute lung injury (ALI), an increasingly devastating human disorder, is characterized by a multitude of lung changes arising from a wide variety of lung injuries. Viral infection is the main cause of morbidity and mortality in ALI and acute respiratory distress syndrome (ARDS) patients. In particular, influenza virus, coronavirus, and other respiratory viruses circulate in nature in various animal species and can cause severe and rapidly spread human infections. Although scientific advancements have allowed for rapid progress to be made to understand the pathogenesis and develop therapeutics after each viral pandemic, few effective methods to treat virus-induced ALI have been described. Recently, stem cell therapy has been widely used in the treatment of various diseases, including ALI."
A fourth study, this one published in Stem Cells and Development and conducted on the ground in China, the original epicenter of the COVID-19 pandemic, found that:
"We have conducted basic research and clinical trials on mesenchymal stem cells (MSCs) for >20 years. One previous study showed that MSCs could induce mature dendritic cells into a novel Jagged-2 dependent regulatory dendritic cell (DC) population, published in Blood. Regulatory DCs (regDCs) play an important role in controlling immune homeostasis and can possess an immunosuppressive ability to induce specific immune tolerance and dampen Th2 type inflammation.
We also reported that MSCs could decrease the differentiation of classical DCs from human CD34+ cells while increasing the differentiation of regDC, published in the Journal of Immunology. Furthermore, interleukin-10 (IL-10) plays an essential role in maintaining the immunomodulatory property of regDC. All these interactions with different dendritic cells lead to a shift of the immune system from Th1 toward Th2 responses.
Based on those results, we believe that ACE2– MSCs could be beneficial for patients with COVID-19. We, therefore, conducted a clinical trial pilot study. The results showed positive effects. MSCs played their immune modulation roles to reverse the lymphocyte subsets. A group of CD14+CD11c+CD11bmid regulatory DC cell population dramatically increased. Meanwhile, the level of TNF-α decreased significantly, and IL-10 increased in the MSC treatment group compared to the placebo control group.
Furthermore, the gene expression profile showed that MSCs were ACE2– and TMPRSS2–, suggesting the MSCs were free from COVID-19 infection. Thus, the intravenous transplantation of MSCs was safe and effective for treatment in patients with COVID-19 pneumonia, especially for patients whose condition was critically severe. In our study, human umbilical cord-derived MSCs (UC-MSCs) were used for transplantation.
A Note on Stem Cell Types
While both autologous and allogeneic stem cells have been used to treat viral infection and to induce regeneration and healing, the latter is the preferred option. Autologous stem cells are sourced from the patient's body and come with accumulated damage due to a lifetime of use and exposure to environmental dangers. Allogeneic stem cells from umbilical cord blood are youthful, highly energetic, and capable of decades of healing and repair.
It is also important to remember that the FDA has approved no stem cell therapies at this time. Any such treatment should be considered experimental only.