CD271 ⁺ Bone Marrow Mesenchymal Stem Cells May Provide a Niche for Dormant Mycobacterium tuberculosis

Abstract

Mycobacterium tuberculosis (Mtb) can persist in hostile intracellular microenvironments evading immune cells and drug treatment. However, the protective cellular niches where Mtb persists remain unclear. We report that Mtb may maintain long-term intracellular viability in a human bone marrow (BM)–derived CD271+/CD45− mesenchymal stem cell (BM-MSC) population in vitro. We also report that Mtb resides in an equivalent population of BM-MSCs in a mouse model of dormant tuberculosis infection. Viable Mtb was detected in CD271+/CD45− BM-MSCs isolated from individuals who had successfully completed months of anti-Mtb drug treatment. These results suggest that CD271+ BM-MSCs may provide a long-term protective intracellular niche in the host in which dormant Mtb can reside.

Bioluminescence for Assessing Drug Potency against Nonreplicating Mycobacterium tuberculosis

“…Our assay can be implemented in in vitro assessments of novel drug combinations against M. tuberculosis and other slowly growing mycobacteria, such as Mycobacterium ulcerans. Additional applications are foreseen in immunology experiments, where the fluorescent reporter can be replaced by luminescence (36), and possibly in in vivo studies that employ whole-body luminescence as a means of detecting tuberculosis infections and monitoring throughout therapy (9,17).…”

Mouse Bone Marrow Sca-1 + CD44 + Mesenchymal Stem Cells Kill Avirulent Mycobacteria but Not Mycobacterium tuberculosis through Modulation of Cathelicidin Expression via the p38 Mitogen-Activated Protein Kinase-Dependent Pathway

“…Previously, it was shown that M. tuberculosis can stay inside MSCs for longer periods of time after antibiotic treatment and can cause active TB at a later time point (7). In the next step, we studied the intracellular survival kinetics of M. tuberculosis, M. bovis BCG, and M. smegmatis in BM-MSCs.…”

“…Recently, M. tuberculosis has also been shown to persist in a mesenchymal subpopulation of bone marrow (BM) stem cells (BMSCs) even after antibiotic treatment (7). The authors have shown that mesenchymal BMSCs may provide a favorable intracellular niche for the persistence of nonreplicating M. tuberculosis and therefore may be important for the maintenance of the dormant phase of the M. tuberculosis life cycle.…”

Effect and mechanism of different ways of transplanting bone marrow mesenchymal stem cells in cardiopulmonary resuscitation in rats

“…BMSCs are pluripotent and have the ability to self-replicate. In vitro studies have found that undifferentiated BMSCs could not induce an allogeneic lymphocyte proliferative response (He et al, 2013;Das et al, 2013), which suggested that BMSCs are naturally non-immunogenic, and provided the basis and prerequisite for its allograft. Some studies confirmed that transplanted BMSC treatment could improve the animal's behavioral score, learning, and memory, induce the secretion of nutritional factors and chemokines, reduce the inflammatory response, reduce the hemorrhage of the surrounding area, apoptosis, and necrosis, and increase microvascular-activated cell self-repair (Krampera et al, 2003;Wei et al, 2012;Babaei et al, 2012;He et al, 2013).…”