Migration and homing of bone-marrow mononuclear cells in chronic ischemic stroke after intra-arterial injection

Abstract

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.

Clinical trial design for stem cell therapies in stroke: What have we learned?

“…26 Ten small clinical studies of intravenous or intra-arterial cell delivery, including 136 subjects, have reported findings. [27][28][29][30][31][32][33][34][35][36] The majority of these were small, single-institution safety and tolerability studies. Only three included a control group, and the value of the control groups is questionable, since in many cases they consisted of patients deemed ineligible for the cell therapy intervention, were not randomised, and did not necessarily undergo any study related procedures.…”

“…Allocation was not always concealed to either patients or investigators. Piecemeal reporting of studies 24,27,28,34 further confuses the interpretation of these reports. Since the main focus was safety, long time windows for cell administration (between days and several months after stroke) were typically permitted.…”

Cell Tracking Technologies for Acute Ischemic Brain Injury

“…105 Sequential imaging in particular may enable the detection of aberrant cell migration and/or proliferation. 106,107 Despite their advantages (cheap, high-throughput), optical/ bioluminescent imaging systems are not suitable for translation into large animal models or the clinic, as they are severely limited by the low penetration of light through tissue of substantial thickness.…”

Cell Therapy of Stroke and Spinal Cord Injury Complications

“…Поскольку хоминг МСК и других стволо-вых клеток в головном мозге ограничен при внутривенной трансплантации, группой бра-зильских исследователей было выполнено внутриартериальное введение 99m Tc -меченных МСК у шести пациентов, перенесших инсульт, с целью добиться возможного увеличения количества клеток, трансплантируемых в го-ловной мозг [23]. Было показано, что хоминг клеток в ишемизированном полушарии на-блюдался уже через 2 ч после развития инсуль-та, однако, хоминг значительно уменьшался через 24 ч после инсульта.…”