Diagrams of the ischemic ROI.

<p>Diagrams of the ischemic core (c, 12 weeks) and ischemic recovery (r, 12 weeks) regions of interest (ROI) determined from T2 maps. FA (A), T₂ (B), T₁ (C), and T_1sat were measured from these ROIs.</p

The temporal profiles of ventricle volumes.

<p>The temporal profiles of relative ventricle volumes in ipsilateral hemisphere (A) and bilateral hemisphere (B) of hUTC or vehicle treated groups, respectively. *, p<0.05, control vs treated groups; **, p<0.01, control vs treated groups.</p

The temporal profiles of lesion volumes.

<p>The temporal profiles of relative lesion volumes in tMCAo rats model following the administration of hUTC or vehicle.</p

The temporal evolution of functional neurobehavioral tests.

<p>The temporal evolution of functional adhesive removal (A), foot-fault (B), and mNSS (C) neurobehavioral tests, respectively, obtained at various times from 1 day to 12 weeks after stroke. **, p<0.01, control vs treated groups based on the global test.</p

Stem Cell Therapy as an Emerging Paradigm for Stroke (STEPS) II

Cell-based therapies represent a new therapeutic approach for stroke. In 2007, investigators from academia, industry leaders, and members of the National Institutes of Health crafted recommendations to facilitate the translational development of cellular therapies as a novel, emerging modality for stroke from animal studies to clinical trials. This meeting was called Stem Cell Therapies as an Emerging Paradigm in Stroke (STEPS) and was modeled on the format of the Stroke Therapy Academic Industry Roundtable (STAIR) meetings. Since publication of the original STEPS guidelines, there has been an explosive growth in the number of cellular products and in the number of new laboratory discoveries that impact the safety and potential efficacy of cell therapies for stroke. Any successful development of a cell product will need to take into consideration several factors, including the preclinical safety and efficacy profile, cell characterization, delivery route, in vivo biodistribution, and mechanism of action. In 2010, a second meeting called STEPS 2 was held to bring together clinical and basic science researchers with industry, regulatory, and National Institutes of Health representatives. At this meeting, participants identified critical gaps in knowledge and research areas that require further studies, updated prior guidelines, and drafted new recommendations to create a framework to guide future investigations in cell-based therapies for stroke

Tracking of In-111-labeled human umbilical tissue-derived cells (hUTC) in a rat model of cerebral ischemia using SPECT imaging

<p>Abstract</p> <p>Background</p> <p>In order to increase understanding of how infused cells work, it becomes important to track their initial movement, localization, and engraftment efficiency following transplantation. However, the available <it>in vivo</it> cell tracking techniques are suboptimal. The study objective was to determine the biodistribution of intravenously administered Indium-111 (In-111) oxine labeled human umbilical tissue-derived cells (hUTC) in a rat model of transient middle cerebral occlusion (tMCAo) using single photon emission computed tomography (SPECT).</p> <p>Methods</p> <p>Rats received 3 million In-111 labeled hUTC (i.v.) 48 hrs after tMCAo. Following the administration of either hUTC or equivalent dose of In-111-oxine (18.5 MBq), animals underwent SPECT imaging on days 0, 1, and 3. Radioactivity in various organs as well as in the stroke area and contralateral hemisphere was determined, decay corrected and normalized to the total (whole body including head) radioactivity on day 0. Immunohistochemical analysis was also performed to confirm the beneficial effects of hUTC on vascular and synaptic density, and apoptosis.</p> <p>Results</p> <p>Most of the radioactivity (43.36±23.07% on day 0) trafficked to the lungs immediately following IV administration of In-111 labeled hUTC (day 0) and decreased drastically to 8.81±7.75 and 4.01±4.52% on days 1 and 3 post-injection, respectively. In contrast, radioactivity measured in the lung of animals that received In-111-oxine alone remained relatively unchanged from day 0 to day 1 (18.38±5.45% at day 0 to 12.59±5.94%) and decreased to 8.34±4.25% on day 3. Significantly higher radioactivity was observed in stroke areas of animals that received In-111 labeled hUTC indicating the presence of cells at the site of injury representing approximately 1% of total administered dose. In addition, there was significant increase in vascular and synaptophysin immunoreactivity in stroke areas of rats that received In-111 labeled hUTC.</p> <p>Conclusions</p> <p>The present studies showed the tracking of In-111 labeled hUTC to the sites of stroke in a rat model of tMCAo using SPECT. Animals treated with In-111 labeled hUTC showed histological improvements, with higher vascular and synaptic densities observed in the ischemic boundary zone (IBZ).</p