Abstract
Bone-marrow derived mesenchymal stem cells (MSCs) exert anti-tuberculosis effects due to their potential to repair damaged tissues and modulate inflammatory immune responses. MSCs were reported to be recruited to the Mycobacterium tuberculosis (Mtb) affected sites in the organism. However, due to limitations of presently applied in vivo imaging techniques the trafficking and biodistribution of MSCs in Mtb-infected organisms is not possible. In the current study MSCs were labeled with superparamagnetic iron oxide nanoparticles (SPIONs) as a negative MR contrast agent for imaging the biodistribution of MSCs in vivo. Trafficking of SPIONs-labeled MSCs was analyzed in a preclinical model of renal tuberculosis in male Chinchilla rabbits (n = 18) following intravenous administration on the days 0, 2, 3, and 7 employing a highly sensitive method of non-linear longitudinal magnetic response (NLR-M2) measurements. Within 48 h after injection, nanoparticle-labeled MSCs accumulated predominantly in lung, spleen, liver tissues, and paratracheal lymph nodes with subsequent decrease over the observation period of 7 days. The recruitment of MSCs to Mtb-affected organs was further proven by immunohistological analysis. NLR-M2 allowed the detection of SPIONs-labeled cells at low concentrations in different organs and tissues giving insights of in vivo mesenchymal stem cells trafficking in organism after TB infection.
Highlights
Tuberculosis (TB) caused by M. tuberculosis (Mtb) is a major threat to the global health and is associated with poor clinical outcome, high transmission rates, high recurrence rates, and drug resistance [1,2,3]
By employing the non-linear response (NLR)-M2 method, we demonstrated that mesenchymal stem cells (MSCs) can accumulate in the primary Mycobacterium tuberculosis (Mtb) affected renal tissues and can traffic to secondary Mtb disseminated areas including paratracheal lymph nodes
NLR-M2 measurements of the aqueous suspension revealed disappearance of the field hysteresis in the ReM2(H) signal from superparamagnetic iron oxide nanoparticles (SPIONs) at increasing temperature and decreasing the frequency of H scans indicating the dynamical character of the hysteresis [39]
Summary
Tuberculosis (TB) caused by M. tuberculosis (Mtb) is a major threat to the global health and is associated with poor clinical outcome, high transmission rates ( in developing countries), high recurrence rates, and drug resistance [1,2,3]. Ongoing scientific research and clinical trials are currently evaluating the potential of anti-TB cell therapies, based on mesenchymal stem cells (MSCs) [9,10,11,12]. Unique properties of MSCs include participation of cells in immunomodulation and antiinflammatory responses [15], pro-angiogenic and anti-apoptotic functions [16] and immuno-evasion that allows the application of allogeneic MSCs in cell therapy and tissue engineering [17, 18]
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