MRI Detects Brain Reorganization after Human Umbilical Tissue-Derived Cells (hUTC) Treatment of Stroke in Rat

Abstract

Human umbilical tissue-derived cells (hUTC) represent an attractive cell source and a potential technology for neurorestoration and improvement of functional outcomes following stroke. Male Wistar rats were subjected to a transient middle cerebral artery occlusion (tMCAo) and were intravenously administered hUTC (N = 11) or vehicle (N = 10) 48 hrs after stroke. White matter and vascular reorganization was monitored over a 12-week period using MRI and histopathology. MRI results were correlated with neurological functional and histology outcomes to demonstrate that MRI can be a useful tool to measure structural recovery after stroke. MRI revealed a significant reduction in the ventricular volume expansion and improvement in cerebral blood flow (CBF) in the hUTC treated group compared to vehicle treated group. Treatment with hUTC resulted in histological and functional improvements as evidenced by enhanced expression of vWF and synaptophysin, and improved outcomes on behavioral tests. Significant correlations were detected between MRI ventricular volumes and histological lesion volume as well as number of apoptotic cells. A positive correlation was also observed between MRI CBF or cerebral blood volume (CBV) and histological synaptic density. Neurological functional tests were also significantly correlated with MRI ventricular volume and CBV. Our data demonstrated that MRI measurements can detect the effect of hUTC therapy on the brain reorganization and exhibited positive correlation with histological measurements of brain structural changes and functional behavioral tests after stroke. MRI ventricular volumes provided the most sensitive index in monitoring brain remodeling and treatment effects and highly correlated with histological and functional measurements.

Human Umbilical Tissue-Derived Cells Promote Synapse Formation and Neurite Outgrowth via Thrombospondin Family Proteins

“…In addition to the functional recovery that was observed after hUTC transplantations, previous studies in animal disease models revealed a strong effect of these cells on the preservation of the neural structures (Lund et al, 2007;Jiang et al, 2012;Moore et al, 2013). Therefore, using the RGC culture system, we next examined the effects of UCM on neuronal survival and neurite outgrowth.…”

“…The umbilical cord is a commonly used cell source for therapeutic purposes due to ease of accessibility without ethical concerns. Several studies report that umbilical cord blood-derived cells can be potentially useful for the treatment of various types of neuro-degeneration Park et al, 2012;Rowe et al, 2012;Achyut et al, 2014). …”

“…The therapeutic potential of hUTC administration was demonstrated in various animal disease models (Lund et al, 2007;Zhang et al, , 2013Jiang et al, 2012;Moore et al, 2013). Delivery of hUTCs into animal models of stroke (Zhang et al, , 2013Jiang et al, 2012;Moore et al, 2013) and retinal degeneration (Lund et al, 2007) has shown that these cells enhance functional recovery and protect neurons from progressive degeneration.…”

“…Delivery of hUTCs into animal models of stroke (Zhang et al, , 2013Jiang et al, 2012;Moore et al, 2013) and retinal degeneration (Lund et al, 2007) has shown that these cells enhance functional recovery and protect neurons from progressive degeneration. The lifespan of the transplanted cells varies with transplantation sites and methods, but the beneficial effects of the cells were measured 8 -12 weeks after treatment (Lund et al, 2007;Jiang et al, 2012;Zhang et al, , 2013.…”

“…Moreover, this culture system was critical in elucidating that astrocytes secrete signals that control synapse formation between neurons (Pfrieger and Barres, 1997;Mauch et al, 2001;Ullian et al, 2001;Christopherson et al, 2005;Kucukdereli et al, 2011;Allen et al, 2012). Thrombospondin (TSP) family proteins TSP1 and TSP2 were identified as the necessary and sufficient astrocyte-secreted synaptogenic proteins that promote a strong increase in excitatory synapses made between RGCs (Christopherson et al, 2005) via their interactions with the neuronal receptor, calcium channel subunit ␣2␦-1 ).…”