Application of mesenchymal stem cells in kidney and urinary tract diseases: literature review and own experience

SummaryIn recent years, cell therapy of diseases of various or-gans and tissues is gaining popularity, including the use of mesenchymal stem cells (MSCs). Many studies have confirmed the presence of pronounced immunoregula-tory properties in this type of cells, which are mediated both by direct action on target cells and by signaling mo-lecules and cytokines. This review is devoted to the pos-sibilities of using MSCs in urological pathology, including a description of the mechanisms of action on the human immune system and the prospects for using this type of cells in experimental and clinical practice. The article presents our own experience in studying the distribution of mesenchymal stem cells in various tissues and organs on a model of kidney tuberculosis in rabbits. Material and methods. The study involved 18 rabbits with kid-ney tuberculosis, which were injected intravenously with mesenchymal stem cells labeled with superparamagnetic iron oxide nanoparticles (SPION), followed by highly sen-sitive nonlinear longitudinal magnetic response imaging (NLR-M2). Results. 48 hours after the injection, MSCs ac-cumulated in the lungs, spleen, liver, paratracheal lymph nodes, and kidneys. Conclusion. The NLR-M2 method allows detecting SPION-labeled cells in various organs and tissues, giving an idea of the mesenchymal stem cells movement in the body.

Abstract 177: Brain-Wide Circuit Dynamics of Post-Stroke Recovery After Optogenetic Stimulation

Background: Post-stroke optogenetic stimulations have been shown to promote functional recovery. However, the cellular and circuit mechanisms underlying such recovery remain unclear. Elucidating key neural circuits in post-stroke recovery will be invaluable for translation of neuromodulation for stroke. Here we used optogenetic functional magnetic response imaging (ofMRI) to examine brain-wide circuit dynamics induced by optogenetic stimulation treatment (OST). Method: Male mice expressing channelrhodopsin (ChR2) in ipsilesional M1 (iM1) layer V excitatory neurons were used. ofMRI were performed on pre-stroke and post-stroke days (PD) 3, 15 and 29. OST were given daily from PD5-15. Sensorimotor tests were conducted one day prior to each ofMRI session. Mice underwent transient middle cerebral artery occlusion (intraluminal suture model, 30 minutes). Two groups were assigned: stim group (mice with 10 days of OST, n=9) and no stim group (mice without OST, n=9). Activation maps were compared between stim and no stim groups to reveal key brain circuits recovered by OST. The expression of plasticity marker GAP43 was examined using western blot. Result: Our results show that 1) Optogenetic excitatory neuronal stimulations in iM1 promotes motor function at PD 14 (P<0.01). 2) At pre-stroke, iM1 stimulations activate expected network including ipsilesional M1, M2, S1, striatum, thalamus, contralateral M1 and cerebellum. 3) At PD3, all mice exhibit a depressed response throughout the brain. 4) At PD15, ipsilesional thalamus and S1 circuits are significantly recovered by OST. Moreover, restoration of thalamic activation is correlated with behavioral recovery in the stim group. 5) At PD15, stimulated mice exhibited higher level of plasticity marker (GAP43) in the ipsilesional thalamus (P<0.05). 6) At PD29, iS1 activation remains stronger in the stim group when compared to no stim group. Conclusion: Our findings revealed key circuits underlying stimulation-induced post-stroke recovery. We found that restoration of cortico-thalamic projections is important in stimulation-induced recovery at early phase post-stroke, while sustained strengthening of ipsilesional cortico-cortical connections may be critical in the later phase of recovery.