Migration and homing of bone-marrow mononuclear cells in chronic ischemic stroke after intra-arterial injection.
Cell-based treatments have been considered a promising therapy for neurological diseases. However, currently there are no clinically available methods to monitor whether the transplanted cells reach and remain in the brain. In this study we investigated the feasibility of detecting the distribution and homing of autologous bone-marrow mononuclear cells (BMMCs) labeled with Technetium-99 m ((99m)Tc) in a cell-based therapy clinical study for chronic ischemic stroke. Six male patients (ages 24-65 years) with ischemic cerebral infarcts within the middle cerebral artery (MCA) between 59 and 82 days were included. Cell dose ranged from 1.25x10(8) to 5x10(8). Approximately 2x10(7) cells were labeled with (99m)Tc and intra-arterially delivered together with the unlabeled cells via a catheter navigated to the MCA. None of the patients showed any complications on the 120-day follow-up. Whole body scintigraphies indicated cell homing in the brain of all patients at 2 h, while the remaining uptake was mainly distributed to liver, lungs, spleen, kidneys and bladder. Moreover, quantification of uptake in Single-Photon Emission Computed Tomography (SPECT) at 2 h showed preferential accumulation of radioactivity in the hemisphere affected by the ischemic infarct in all patients. However, at 24 h homing could only distinguished in the brains of 2 patients, while in all patients uptake was still seen in the other organs. Taken together, these results indicate that labeling of BMMCs with (99m)Tc is a safe and feasible technique that allows monitoring the migration and engraftment of intra-arterially transplanted cells for at least 24 h.
Hospital Universitário Clementino Fraga Filho, Departamento de Radiologia, subsolo, Universidade Federal do Rio de Janeiro, Ilha do Fundão, Rio de Janeiro, Brazil. lmirian@hucff.ufrj.br
Lea Mirian
LM
Barbosa da Fonseca
Bianca
B
Gutfilen
Paulo Henrique
PH
Rosado de Castro
Valeria
V
Battistella
Regina C S
RC
Goldenberg
Tais
T
Kasai-Brunswick
Claudia L R
CL
Chagas
Eduardo
E
Wajnberg
Angelo
A
Maiolino
Sérgio
S
Salles Xavier
Charles
C
Andre
Rosalia
R
Mendez-Otero
Gabriel R
GR
de Freitas
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D001854:Bone Marrow Cells / Q000000981:diagnostic imaging / Q000378:metabolism / Q000502:physiology*; D016026:Bone Marrow Transplantation / Q000379:methods*; D002545:Brain Ischemia / Q000150:complications* / Q000000981:diagnostic imaging; D002465:Cell Movement / Q000502:physiology*; D002544:Cerebral Infarction / Q000000981:diagnostic imaging / Q000209:etiology* / Q000601:surgery*; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007269:Injections, Intra-Arterial / Q000379:methods; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013667:Technetium; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D014182:Transplantation, Autologous / Q000379:methods; D051598:Whole Body Imaging / Q000379:methods; D055815:Young Adult
D015703:Antigens, CD; D013667:Technetium