Differential Clearance of Rat and Human Bone Marrow-Derived Mesenchymal Stem Cells From the Brain After Intra-arterial Infusion in Rats.

Intra-arterial (IA) delivery of bone marrow-derived mesenchymal stem cells (BM-MSCs) has shown potential as a minimally invasive therapeutic approach for stroke. The aim of the present study was to determine the whole-body biodistribution and clearance of technetium-99m ((99m)Tc)-labeled rat and human BM-MSCs after IA delivery in a rat model of transient middle cerebral artery occlusion (MCAO) using single-photon emission computed tomography (SPECT). Our hypothesis was that xenotransplantation has a major impact on the behavior of cells. Male RccHan:Wistar rats were subjected to sham operation or MCAO. Twenty-four hours after surgery, BM-MSCs (2 × 10(6) cells/animal) labeled with (99m)Tc were infused into the external carotid artery. Whole-body SPECT images were acquired 20 min, 3 h, and 6 h postinjection, after which rats were sacrificed, and organs were collected and weighed for measurement of radioactivity. The results showed that the majority of the cells were located in the brain and especially in the ipsilateral hemisphere immediately after cell infusion both in sham-operated and MCAO rats. This was followed by fast disappearance, particularly in the case of human cells. At the same time, the radioactivity signal increased in the spleen, kidney, and liver, the organs responsible for destroying cells. Further studies are needed to demonstrate whether differential cell behavior has any functional impact.

Intra-arterial infusion of human bone marrow-derived mesenchymal stem cells results in transient localization in the brain after cerebral ischemia in rats.

Cell therapies from various sources have been under intense research in stroke. Efficient homing of the cells to the injured brain without complications is necessary to realize the therapeutic potential of cell therapy. Intra-arterial (IA) infusion of cells bypasses the filtering organs and directs the cells to the target area more efficiently. Here we studied the biodistribution of human bone marrow-derived mesenchymal stromal/stem cells (BMMSCs) after a direct infusion into the external carotid artery (ECA) in rats. Cells, which were cultured without animal-derived agents and also treated with a proteolytic enzyme to transiently modify cell surface adhesion proteins, were infused 24 h after transient middle cerebral artery occlusion (MCAO). SPECT imaging was used immediately after cell infusion and 24 h thereafter to track (111)In-oxine-labeled BMMSC in sham-operated and MCAO rats. IA infusion of BMMSCs in rats resulted in immediate cell entrapment in the brain, but the majority of the signal disappeared during the next 24 h and relocated to the internal organs. In MCAO rats, radioactivity counts 24 h after infusion were higher in the ischemic hemisphere compared to the contralateral hemisphere. Our results showed that IA infusion through ECA is a safe and efficient administration route for BMMSCs resulting in a transient localization of cells in the rat brain.