Intravenous and intra-arterial administration of bone marrow mononuclear cells after focal cerebral ischemia: Is there a difference in biodistribution and efficacy?

Abstract

Intravascular delivery of cells has been increasingly used in stroke models and clinical trials. We compared the biodistribution and therapeutic effects of bone marrow mononuclear cells (BMMCs) delivered by intra-arterial (IA) or intravenous (IV) injection after cortical ischemia. For the biodistribution analyses, BMMCs were labeled with (99m)Technetium ((99m)Tc). At 2 h, gamma-well counting of the brain and of the other organs evaluated did not show differences between the non-ischemic and ischemic groups or between injection routes, and the organs with the highest uptake were the liver and lungs, with low uptake in the brain. At 24 h, the liver maintained the highest activity, and a marked decrease was seen in pulmonary uptake in all groups. At this time point, although the activity in the brain remained low, the lesioned hemisphere showed greater homing than the contralateral hemisphere, for both the IV and IA ischemic groups. Histological analysis by CellTrace labeling indicated similar homing between both routes in the peri-infarct region 24 h after transplantation and functional recovery was observed in both groups up to 11 weeks after the lesion. In conclusion, transplantation of BMMCs by IA or IV routes may lead to similar brain homing and therapeutic efficacy after experimental stroke.

Intra-Arterial Delivery Is Not Superior to Intravenous Delivery of Autologous Bone Marrow Mononuclear Cells in Acute Ischemic Stroke

“…In a prior report, we found no differences in the biodistribuition of MNCs that were derived from bone marrow before versus after stroke when the MNCs were examined at 24 hrs after injection but we did not examine earlier time points 16 . In another relevant study, Vasconcelos-dos-Santos et al labeled donor-derived bone marrow MNCs with 99m Tc 7 and found no difference in labeling in the brain or other organs from early time points to 24 hrs after delivery and similarly found that both IV and IA led to similar effects on stroke recovery 7 .…”

“…IV administration is least invasive but given pulmonary sequestration may not deliver cells to the same extent to the brain 2 . Few studies have directly compared delivery routes and the results are conflicting 6, 7 . In this study, we performed a direct comparison of the effects of IV versus IA delivery of autologous MNCs in the rodent stroke model and assessed for potential differences in biodistribution, behavioral outcome, and selected mechanistic effects.…”

Strategies for CNS repair following TBI

“…Kamiya and colleagues were able to show decreased lesion size and motor function when compared to control animals with intra-arterial but not with intravenous administration (Kamiya et al, 2008). Alternatively, other studies comparing intra-arterial with intravenous administration of BM-MNC have shown no difference in behavioral/functional or structural outcomes in several animal models (Vasconcelos-dos-Santos et al, 2012;Yang et al, 2013). In addition, intravenous administration was found to cause potentially beneficial attenuation of cytokines with greater decreases in IL-1β and increases in IL-10 when compared to intraarterial administration (Yang et al, 2013).…”

Stem cell therapy in intracerebral hemorrhage rat model

“…Importantly, the latter adversity can be surpassed with slower injection rates [143] , a generally overlooked variable. It was reported that carotid artery delivery favors cell migration to the brain if compared to tail vein delivery route [146] . However, no differences in this aspect were seen when comparing carotid artery and jugular vein stem cell injections [147] .…”