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

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 distinguishing 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 BM-MSCs 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 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

Complicated septic shock caused by Achromobacter xylosoxidans bacteremia

Infections caused by Achromobacter xylosoxidans cause significant morbidity and mortality in debilitated individuals. Eradication of these infections requires prolonged therapy with antimicrobial agents and removal of any infected central venous catheter. The outcome is usually poor in patients with high risk malignancy, septic complications, and/or multi-organ dysfunction

Candidaemia in patients with haematological disorders and stem cell transplant

The incidence of non-albicans species of Candida has recently increased, especially in patients with malignant haematological disorders receiving fluconazole prophylaxis. A retrospective study of patients who developed candidaemia at Riyadh Armed Forces Hospital between January 1992 and December 2002 was carried out. Thirty one episodes of candidaemia occurred in 27 patients with a variety of haematological disorders. Twenty-four episodes were caused by non-albicans species of Candida and only 7 episodes were caused by C.albicans. The most frequent underlying haematological disorders were acute myeloid leukaemia (AML) followed by acute lymphoblastic leukaemia (ALL). The main predisposing factors for the development of candidaemia were: broad spectrum antibiotics, central venous catheters, neutropenia, cytotoxic chemotherapy, coexisting bacterial infections, steroid therapy, relapsing or untreated primary disease and fluconazole prophylaxis. Eight episodes were complicated by chronic disseminated candidiasis. Amphotericin-B and amBisome were used in the treatment of Candida infections. The treatment was successful in 86% of the episodes of C.albicans and 50% of the episodes due to non-albicans species of Candida. The highest mortality rate was encountered with C.tropicalis infections. Candidaemia is an important cause of mortality and morbidity in patients with malignant haematological disorders and stem cell transplant. The predominance of nonalbicans species of Candida especially C.krusei and C.tropicalis is alarming. The early administration of appropriate antifungal therapy and the removal of infected intravascular catheters improve the outcome considerably. Keywords: Candida; chronic disseminated candidiasis; acute myeloid leukaemia; acute lymphoblastic leukaemia; stem cell transplant Libyan Journal of Medicine Vol. 1 (2) 2006: pp. 140-15