Analysis of the lung showed a first passage effect that resulted in significantly greater engraftment of cells by IV than by IA administration at 1 hour

Analysis of the lung showed a first passage effect that resulted in significantly greater engraftment of cells by IV than by IA administration at 1 hour. (MRI) consisting of T2 weighted image (T2WI), T2*weighted image (T2*WI), susceptibility weighted image (SWI), and diffusion weighted image of rat brain were obtained prior to and Rabbit Polyclonal to PDCD4 (phospho-Ser457) at 1, 6, 24, and 48 hours post-implantation. After final MRI, rats were sacrificed and grafted cells were analyzed in brain and lung specimen using Prussian blue and immunohistochemical staining. == Results == Grafted cells appeared as dark signal intensity regions at the peri-lesional zone. In IA group, dark signals in peri-lesional zone were more prominent compared with IV group. Cycloheximide (Actidione) SWI showed largest dark signal followed by T2*WI and T2WI in both IA and IV groups. On Prussian blue staining, IA administration showed substantially increased migration and a large number of transplanted hBM-MSCs in the target brain than IV administration. The Prussian blue-positive cells were not detected in SPIO and control groups. == Conclusion == In a rat photothrombotic model of ischemic stroke, selective IA administration of human mesenchymal stem cells is more effective than IV administration. MRI and histological analyses revealed the time course of cell migration, and the numbers and distribution of hBM-MSCs delivered into the brain. Keywords:MRI, Mesenchymal stem cell, Photothrombotic cerebral infarction, Superparamagnetic iron oxide, Intravascular == INTRODUCTION == Human bone marrow-derived mesenchymal stem cells (hBM-MSCs) transplantation following experimental stroke promotes functional recovery in animal models39,66,67). The transplanted may potentially mediate recovery through differentiation into functional neuronal cells (microglia, new neural stem cells, neurons, oligodendrocytes, and astrocytes)10,46,63,65), induction of neurogenesis14,57), synapse formation (synaptogenesis)55), and neuroprotection (inhibition of apoptosis, inflammation and demyelination while promoting astrocyte survival)13,39,40,56). By promoting angiogenesis15), the Cycloheximide (Actidione) Cycloheximide (Actidione) hBM-MSCs may help to restore cerebral blood flow and the blood brain barrier8,9). Perhaps underlying these diverse mechanisms is the capacity of hBM-MSC to promote endogenous repair and regeneration through induction of cytokines and trophic factors such as brain-derived neurotrophic factor, insulin-like growth factor-1, nerve growth factor, fibroblast growth factor-2, vascular endothelial growth factor and stromal cell-derived factor-1 (SDF-1)8,13,16,17,20,40,56). The route chosen for delivery of cells may influence the migration and final destination of the transplanted cells. Direct intracerebral26,29), intravascular13,15,18,55,59), intrathecal41), and intraventricular32)delivery of cells for transplantation have been tested. Intravascular delivery presents such advantages as safety and wide distribution of stem cells within the ischemic penumbra as compared to other method. Intravascular transplantation may proceed by either intra-arterial (IA) or intravenous (IV) delivery. Experimentally, the IV13,15,18), and IA55,59)routes have been used to investigate homing capabilities and mechanisms of the MSCs, Cycloheximide (Actidione) and to show that IV administration results in greater cell trapping by systemic organs such as lung, liver, spleen than IA Cycloheximide (Actidione) injection. These observations may be relevant to achieving therapeutic densities of hBM-MSCs in a rat’s photothrombotic cerebral infarction model22,47). IA administration of stem cells to the injured or ischemic brain was may be significantly more effective in achieving delivery of cells than by the IV route26,38,42). Previous studies have demonstrated that IA administration of stem cells to the injured brain or ischemic brain was significantly more effective than the IV route, however, there was no study that showed MRI and pathologic correlation analysis. In present study, we evaluated the migration and distribution of hBM-MSCs transplanted by IA and IV injection routes into the photothrombotic cerebral infarction region of the rat during 48 hours after cell transplantation (5 days after infarction). Here, we present the magnetic resonance imaging (MRI) and pathologic analyses performed in parallel with the treatment. == MATERIALS AND METHODS == == Ethical statement == Rats were maintained in accordance with guidelines of the Institutional Animal Ethics Committee at our institution. The Institutional Review Board of CAUH (CAUMD 11-0020) approved this study. == Cell culture and labeling == Adult bone marrow contains two types.