title: Differential Clearance of Rat and Human Bone Marrow-Derived Mesenchymal Stem Cells From the Brain After Intra-arterial Infusion in Rats.
abstract: 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.
authors.affiliation: Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland.
authors.forename: Joonas
authors.initials: J
authors.lastname: Khabbal
authors.forename: Erja
authors.initials: E
authors.lastname: Kerkelä
authors.forename: Bhimashankar
authors.initials: B
authors.lastname: Mitkari
authors.forename: Mari
authors.initials: M
authors.lastname: Raki
authors.forename: Johanna
authors.initials: J
authors.lastname: Nystedt
authors.forename: Ville
authors.initials: V
authors.lastname: Mikkonen
authors.forename: Kim
authors.initials: K
authors.lastname: Bergström
authors.forename: Saara
authors.initials: S
authors.lastname: Laitinen
authors.forename: Matti
authors.initials: M
authors.lastname: Korhonen
authors.forename: Jukka
authors.initials: J
authors.lastname: Jolkkonen
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D064593:Heterografts; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells; D011859:Radiography; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000000981:diagnostic imaging / Q000628:therapy*