Impaired functional recovery of endothelial colony-forming cells from moyamoya disease in a chronic cerebral hypoperfusion rat model

Abstract

<jats:sec><jats:title>OBJECTIVE</jats:title><jats:p>Endothelial colony-forming cells (ECFCs) isolated from pediatric patients with moyamoya disease (MMD) have demonstrated decreased numbers and defective functioning in in vitro experiments. However, the function of ECFCs has not been evaluated using in vivo animal models. In this study, the authors compared normal and MMD ECFCs using a chronic cerebral hypoperfusion (CCH) rat model.</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>A CCH rat model was made via ligation of the bilateral common carotid arteries (2-vessel occlusion [2-VO]). The rats were divided into three experimental groups: vehicle-treated (n = 8), normal ECFC-treated (n = 8), and MMD ECFC-treated (n = 8). ECFCs were injected into the cisterna magna. A laser Doppler flowmeter was used to evaluate cerebral blood flow, and a radial arm maze test was used to examine cognitive function. Neuropathological examinations of the hippocampus and agranular cortex were performed using hematoxylin and eosin and Luxol fast blue staining in addition to immunofluorescence with CD31, von Willebrand factor, NeuN, myelin basic protein, glial fibrillary acidic protein, and cleaved caspase-3 antibodies.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>The normal ECFC-treated group exhibited improvement in the restoration of cerebral perfusion and in behavior compared with the vehicle-treated and MMD ECFC-treated groups at the 12-week follow-up after the 2-VO surgery. The normal ECFC-treated group showed a greater amount of neovasculogenesis and neurogenesis, with less apoptosis, than the other groups.</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS</jats:title><jats:p>These results support the impaired functional recovery of MMD ECFCs compared with normal ECFCs in a CCH rat model. This in vivo study suggests the functional role of ECFCs in the pathogenesis of MMD.</jats:p></jats:sec>

Therapeutic Potential of Endothelial Colony-Forming Cells in Ischemic Disease: Strategies to Improve their Regenerative Efficacy

“…Third, ECFCs’ angiogenic behavior is typically compromised in the presence of cardiovascular risk factors that predispose to the onset of ischemic disorders; this further contributes to discouraging the use of circulating ECFCs for autologous cell therapy [ 15 , 59 , 110 , 115 ]. For instance, the frequency and/or vasoreparative potential of circulating ECFCs are remarkably reduced with CAD [ 120 ], aging [ 121 ], diabetes [ 122 ], abdominal aortic aneurysm [ 123 ], venous thromboembolic disease [ 124 ], congenital diaphragmatic hernia [ 125 ], systemic lupus erythematosus [ 126 ], and the pediatric Moyamoya disease (MMD) [ 127 ]. In addition, ECFCs’ angiogenic behaviour is impaired in patients affected by human immunodeficiency virus (HIV), which has long been associated with cardiovascular disorders [ 128 ].…”

URB597 protects against NLRP3 inflammasome activation by inhibiting autophagy dysfunction in a rat model of chronic cerebral hypoperfusion

“…A substantial amount of evidence indicates that chronic cerebral hypoperfusion (CCH), a state of chronic cerebral blood flow reduction, is associated with several cerebrovascular and neurodegenerative disorders including Alzheimer's disease (AD), carotid stenosis/occlusion, cerebral arteriovenous malformation, dural arteriovenous fistula, moyamoya disease and cerebral small vessel disease [1][2][3][4][5][6]. In our previous study [7][8][9][10][11], we found that CCH may contribute to neuronal apoptosis, cognitive impairment, chronic neuroinflammatory responses and abnormal excessive autophagy in the frontal cortex and hippocampus of rats, resulting in cerebral ischemic damage.…”

Human endothelial colony-forming cells in regenerative therapy: A systematic review of controlled preclinical animal studies

“…ECFCs were derived predominantly from human umbilical cord blood (n = 55; 83%) while remaining studies expanded ECFCs from peripheral blood (n = 11; 17%) of healthy adult volunteers. [11][12][13][14][15][16][17][18][19][20][21] One study used ECFCs collected from human placenta. 22 Most (n = 59, 89%) studies administered ECFCs while 12 studies also included experiments with derivative products such as extracellular vesicles (ie, exosomes [23][24][25][26][27] or microvesicles 11,28 ), and/or conditioned media 7,[29][30][31][32] (Table 1).…”

“…Some organ injury categories included multiple types of organ dysfunction, while other categories were more homogenous in the induction of organ dysfunction. In particular, hind limb ischemia (n = 23), [16][17][18]21,22,32,33,36,39,[44][45][46][47][48][49][50][51][52][53][54][55][56][57] cerebral ischemia (n = 7), 12,37,[58][59][60][61][62] and acute renal injury (n = 6) 11,23,26,27,30,63 studies represent the three most common models of organ dysfunction (Table 4) Multiple system refers to composite measures such as exercise capacity and changes in weight that cannot be isolated to an individual organ system. b Some studies reported on outcomes related to one or more organ systems and the total number of studies is greater than 66.…”