Abstract
IntroductionHuman umbilical tissue-derived cells (hUTC) are a promising source of cells for regenerative treatment of stroke. In this study, we tested the efficacy of hUTC in experimental stroke and whether multiple injections of hUTC provide additional therapeutic benefits as compared to a single injection.MethodsAdult male Wistar rats were subjected to 2 hours of middle cerebral artery occlusion (MCAo), and randomly selected animals were injected (i.v) with 3×106 hUTC or with vehicle control (at day: 1, 1&3 or 1&7 after MCAo, n = 8–9/group). A battery of functional outcome tests was performed at days 1, 7, 14, 21, 28, 35, 42, 49, 56 and 63 after MCAo. Rats were sacrificed at 63 days after MCAo and lesion volumes were measured. To investigate the underlying mechanism of hUTC treatment of stroke, Von Willebrand Factor (vWF), and Synaptophysin immunostaining were performed.ResultsAll hUTC treated groups, single or multiple injections, had better functional recovery compared to control (p<0.01). There was no statistically significant difference between a single and multiple injections of hUTC (p = 0.23) or between different multiple injections groups (p>0.07) in functional outcome. All hUTC treatment groups showed significant increases in Synaptophysin, vascular density and perimeter compared to the control group (p<0.05). There was no statistically significant difference between a single and multiple injections of hUTC or between the two groups of multiple injections in all immunohistochemical measurements (p>0.1).ConclusionhUTC treatment significantly improves long term functional outcome after stroke and promotes vascular density and synaptic plasticity. At the proscribed doses, multiple injections of hUTC were not superior to single injection therapy in both functional outcome and histological assessments.
Highlights
Human umbilical tissue-derived cells are a promising source of cells for regenerative treatment of stroke
There is a paucity of studies testing whether multiple injections of cells are superior to single injection [6]
This study investigated the efficacy of Human umbilical tissue-derived cells (hUTC) treatment on the functional recovery, measured from three behavioral tests, and the histological evaluation
Summary
Human umbilical tissue-derived cells (hUTC) are a promising source of cells for regenerative treatment of stroke. We tested the efficacy of hUTC in experimental stroke and whether multiple injections of hUTC provide additional therapeutic benefits as compared to a single injection. There is a clear and unmet need to develop effective treatments with a wide therapeutic window capable of restoring neural function and reducing disabilities associated with stroke. Cell-based treatments of stroke include neural stem cells, umbilical cord blood cells, bone marrow-derived mesenchymal stem cells (MSCs) [7,8,9,10], and human umbilical tissue-derived cells (hUTC) are promising sources of cells for regenerative treatment of stroke [11,12,13]. In contrast to other cell types (MSCs, embryonic stem cells etc.), hUTC are obtained by non-invasive methods and their use does not evoke ethical concerns
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