Mesenchymal Stem Cells — Their Antimicrobial Effects and Their Promising Future Role as Novel Therapies of Infectious Complications in High Risk Patients

Abstract

Mesenchymal stem cells (MSCs) are heterogeneous progenitor cells that have the capacity of self-renewal and multi-lineage differentiation. These adult stem cells can be derived from several sources including bone marrow (BM), peripheral blood, cord blood, placenta, amniotic fluid, skin and adipose tissue. They have certain distin‐ guishing features and their immunomodulatory and immunosuppressive properties enable them to have several therapeutic and clinical applications. Recently, MSCs have gained enormous potential as they can potentially cure various intractable and chronic diseases and as they have shown effectiveness in the treatment of various infections in animal models and in early clinical trials. MSCs are essential constituents of the framework that supports organ integrity and tissue barriers. Suppression of both T and B cells allows them to be major players in the innate response to bacterial infection and in controlling inflammatory response. Human BM-MSCs possess direct antibacterial activity against Gram-negative bacilli and they have been shown to improve survival and reduce mortality in animal models having septic complications. BM-MSCs are effective in treating sepsis and acute respiratory distress syndrome in high-risk patients such as those with malignant hematological disorders, recipients of solid organ and hematopoietic stem cell transplantation (HSCT) and patients receiving advanced level of care in intensive care units. Additionally, human BMMSCs can act as drug delivery vehicles by enhancing the effectiveness of conventional antimicrobials and thus they may prevent the evolution of drug-resistant microbes. MSCs contain a subset of interleukin-17+ that is capable of inhibiting the growth of © 2015 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Candida albicans (C. albicans). Also, CD 271+ BM-MSCs may provide a long-term protective intracellular niche in the host where Mycobacterium tuberculosis (M.TB) organisms remain viable but in a dormant state. Two recent clinical trials in humans that included 57 patients have shown that autologous transplantation of MSCs can successfully treat multidrug resistant (MDR) strains of M.TB. Animal studies have demonstrated that MSCs enhance host defenses against malaria. MSC therapy improves liver function and promotes hepatocellular regeneration in patients with hepatic fibrosis caused by schistosomiasis. Transplantation of MSCs has been shown to reverse right ventricular dilatation, cardiomyopathy and advanced cardiac involvement caused by Trypanosoma cruzi infection. Autologous MSC transfusion in patients having liver cirrhosis secondary to hepatitis B or C infection improves liver function tests. Transfusion of MSCs can confer resistance to human immunodeficiency virus (HIV)and may restore immune reconsti‐ tution in infected individuals. Also, MSCs obtained from Wharton's jelly of the umbilical cord may become a novel therapy to reverse immune deficiency in individuals infected with HIV1, particularly immune non-responders. Additionally, recent studies have demonstrated that hematopoietic stem cell-based gene therapy may ultimately offer a curative therapeutic option for HIV disease. MSCs improve murine models of acute myocarditis induced by infection with Coxsackie B3 virus. There is low risk of transmission of human herpes viruses by transplantation of MSCs from healthy seropositive donors. Cytomegalovirus (CMV) infection impairs the immunosuppressive and antimicrobial effector functions of human MSCs, thus overt CMV infection in recipients of HSCT may undermine the clinical efficacy of MSCs in treating graft versus host disease (GVHD). The therapeutic applications of BM-MSCs in recipients of HSCT include: prevention and treatment of GVHD, induction of faster engraftment, immune reconstitution, healing of inflammation as well as prevention and treatment of various infectious complications. Thus, taking into consideration the remarkable success in the utilization of MSCs in the treatment of various infections in animal models and in human clinical trials, it is reasonable to predict that MSCS may become very promising novel therapeutic modalities as they have the potential to control or even cure various infectious complications in high-risk patients. However, the field is still in its infancy and plenty of research and clinical trials are required to refine their therapeutic indications. Banking of MSCs is vital to make them available for use. Finally; strict guidelines, standardization techniques and quality control measures are urgently required for collection, cryopreservation and clinical utilization of MSCs.