Homing Of Bone Marrow-derived Stem Cells Research Articles

CXCL12/SDF-1-Dependent Retinal Migration of Endogenous Bone Marrow-Derived Stem Cells Improves Visual Function after Pharmacologically Induced Retinal Degeneration.

Mobilized bone marrow-derived stem cells (BMSC) have been discussed as an alternative strategy for endogenous repair. Thereby, different approaches for BMSC mobilization have been pursued. Herein, the role of a newly discovered oligonucleotide for retinal homing and regeneration capability of BMSCs was investigated in the sodium iodate (NaIO3) model of retinal degeneration. Mobilization was achieved in GFP-chimera with NOX-A12, a CXC-motif chemokine ligand 12 (CXCL12)/stromal cell-derived factor 1 (SDF-1)-neutralizing L-aptamer. BMSC homing was directed by intravitreal SDF-1 injection. Visual acuity was measured using the optokinetic reflex. Paraffin cross sections were stained with hematoxylin and eosin for retinal thickness measurements. Immunohistochemistry was performed to investigate the expression of cell-specific markers after mobilization. A single dose of NOX-A12 induced significant mobilization of GFP+ cells which were found in all layers within the degenerating retina. An additional intravitreal injection of SDF-1 increased migration towards the site of injury. Thereby, the number of BMSCs (Sca-1+) found in the damaged retina increased whereas a decrease of activated microglia (Iba-1+) was found. The mobilization led to significantly increased visual acuity. However, no significant changes in retinal thickness or differentiation towards retinal cell types were detected. Systemic mobilization by a single dose of NOX-A12 showed increased homing of BMSCs into the degenerated retina, which was associated with improved visual function when injection of SDF-1 was additionally performed. The redistribution of the cells to the site of injury combined with their observed beneficial effects support the endogenous therapeutic strategy for retinal repair.

Abstract 452: Impact of Aryl Hydrocarbon Receptor Agonist, Leflunomide, on Components of Stem Cells in the Setting of Renal Ischemia-Reperfusion Injury

The aryl hydrocarbon receptor (AHR) has emerged as a regulator of bone marrow-derived stem cells (BMDSCs). Further, mobilization and homing of BMDSCs into the ischemic-reperfused kidney contribute importantly to the repair and recovery of the injured tissue. We tested the hypothesis that the recently described non-dioxin AHR agonist, leflunomide, mobilizes BMDSCs into the ischemic-reperfused kidney in association with reduction in cell death. Accordingly, male mice were treated with leflunomide (40 mg/kg; i.p.). Thereafter, the right kidney of each animal was subjected to ischemia (45 min) followed by reperfusion (4 hr) while the left kidney served as sham control; vehicle-treated animals served as controls. Peripheral blood and renal cells prepared from kidneys of experimental groups were subjected to flow cytometry-based assays using markers for endothelial progenitor cells (EPCs; Sca1 + /CD31 + ), mesenchymal stem cells (MSCs; Sca1 + /CD11b - ) and hematopoietic stem cells (HSCs; Sca1 + /CD11b + ). Compared to the vehicle-treated mice, peripheral blood of leflunomide-treated mice showed significantly higher levels of MSCs and HSCs with the effect more marked for the latter. On the other hand, the ischemic-reperfused, but not sham, kidneys of leflunomide-treated animals displayed significant and similar increase in the level of each component of BMDSCs compared to their vehicle-treated counterparts. Further, leflunomide-treated mice displayed preservation of mitochondrial membrane potential as well as decreased apoptosis and necrosis compared to vehicle-treated ischemic-reperfused or sham kidneys. Collectively, the results indicate that AHR stimulation may represent a novel renoprotective mechanism likely involving mobilization and recruitment of components of Sca1+ stem cells into the damaged kidney.

Stem cell mobilisation for myocardial repair

Background: The idea that autologous bone marrow derived stem cells (BMCs) can transdifferentiate into cardiomyocytes or vascular cells has been challenged in several scientific reports. Objective/methods: This review summarises conditions for stem cell mobilisation, their use for therapeutic approaches to prevent ischaemic cardiomyopathy after acute myocardial infarction and current clinical trials. Mechanisms for mobilisation and homing of BMCs are discussed. Results/conclusions: The improvement in cardiac function after migration of autologous BMCs to the heart can be explained by their paracrine effects, inducing angiogenesis and preventing ischaemic myocardium from apoptosis. These effects may explain why the number of circulating BMCs is directly correlated with cardiovascular risk and life expectancy. Exercise and hormones are physiological stimuli for the mobilisation of BMCs, whereas cardiovascular risk factors severely reduce their number and functions. Current cardiovascular medications increase the amounts of autologous BMCs.