Evaluation of the Biodistribution of Mesenchymal Stem Cells in a Pre-clinical Renal Tuberculosis Model by Non-linear Magnetic Response Measurements

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.

Targeting Brain Tumors with Mesenchymal Stem Cells in the Experimental Model of the Orthotopic Glioblastoma in Rats

“…In the solution prepared for injection, SPIONs form a highly dispersed system of aggregates with a mean content of 160 nanoparticles per aggregate and with the stem cells containing on average 8.27 × 10 4 aggregates each [ 17 ]. As shown before [ 21 ], SPIONs in an aggregate are strongly magnetically coupled and therefore, the aggregates represent magnetically active centers rather than singular SPIONs.…”

“…SPIONs were prepared as previously described [ 17 ]. The rat MSCs that reached a monolayer were incubated overnight with nanoparticles at a concentration of 150 μg/mL in a CO 2 incubator.…”

“…To quantify the data of the NLR -M 2 measurements, the obtained dependences Re M 2 ( H,T ) and Im M 2 ( H,T ) were processed with the formalism based on the numerical solution of the kinetic Fokker–Planck equation for superparamagnetic particles, as it has been done previously in the study of the biodistribution of mesenchymal stem cells administrated in rabbits [ 17 ]. The output of the formalism is the function describing the magnetic field dependence of the real and imaginary parts of the nonlinear response to be applied for fitting the signal.…”

“…In the current study the biodistribution and tumor-targeting potential of MSCs was assessed in a preclinical orthotopic model of C6 glioblastoma in Wistar rats. MSCs were labeled with superparamagnetic iron oxide nanoparticles (SPIONs) that have been previously demonstrated as a highly sensitive MR negative contrast agent (due to their unique physico–chemical properties) with a low cytotoxicity profile [ 17 , 18 , 19 , 20 ]. The biodistribution of SPIONs-labeled MSCs was determined by a highly sensitive method of longitudinal nonlinear response (NLR- M 2 ) to a weak ac magnetic field, in which the second harmonic of magnetization M 2 in dependence on the steady field H parallel to the ac field was registered [ 17 , 21 ].…”

“…MSCs were labeled with superparamagnetic iron oxide nanoparticles (SPIONs) that have been previously demonstrated as a highly sensitive MR negative contrast agent (due to their unique physico–chemical properties) with a low cytotoxicity profile [ 17 , 18 , 19 , 20 ]. The biodistribution of SPIONs-labeled MSCs was determined by a highly sensitive method of longitudinal nonlinear response (NLR- M 2 ) to a weak ac magnetic field, in which the second harmonic of magnetization M 2 in dependence on the steady field H parallel to the ac field was registered [ 17 , 21 ]. Herein, we report the glioma-tropism of the administered MSCs and the feasibility of the SPIONs delivery to the tumor site.…”