Intra-carotid arterial transfusion of circulatory-derived autologous endothelial progenitor cells in rodent after ischemic stroke — evaluating the impact of therapeutic time points on prognostic outcomes

Abstract

Background: This study tested the optimal time point for left intra-carotid arterial (LICA) administration of circulatory-derived autologous endothelial progenitor cells (EPCs) for improving the outcome in rat after acute ischemic stroke (IS). Methods and Results: Adult-male SD rats (n=70) were equally categorized into group 1 (sham-operated control), group 2 (IS), group 3 (IS+EPCs/1.2x106 cells/by LICA administration 3h after IS), group 4 (IS+EPCs/LICA administration post-day-3 IS), group 5 (IS+EPCs/LICA administration post-day-7 IS), group 6 (IS+EPCs/LICA administration post-day-14 IS) and group 7 (IS+EPCs/LICA administration post-day-28 IS). The brain-infarct volume (BIV) (at day 60/MRI) was lowest in group 1, highest in group 2 and significantly progressively increased from groups 3 to 7, whereas among the IS animals, the neurological function was significantly preserved in groups 3 to 6 than in groups 2 and 7 post-day-60 IS (all p<0.0001). By day 60, the endothelial cell markers at protein and cellular levels, and number of small vessels exhibited an opposite pattern of BIV among the groups (all p<0.0001). The protein and cellular levels of inflammation, and protein levels of oxidative stress, autophagy and apoptosis, were highest in group 2, lowest in group 1 and progressively increased from groups 3 to 7 (all p<0.0001). The angiogenesis biomarkers at protein and cellular levels were significantly progressively increased from groups 1 to 3, then significantly progressively decreased from groups 4 to 7 (all p<0.0001). Conclusion: Early EPC administration provided better benefits on improving functional/image/molecular-cellular outcomes after acute IS in rat.

Additional benefit of induced pluripotent stem cell-derived mesenchymal stem cell therapy on sepsis syndrome-associated acute kidney injury in rat treated with antibiotic

“…In this way, our finding corroborated with the finding of our previous studies [31,32,38,39]. Interestingly, our other previous studies have revealed that early administration of stem cells was more advantageous than the late administration of stem cells on protecting the organ from ischemia and hypoxia induced damage [40,41]. Of importance was that the result of the present study identified that early administration was better than late administration of iPS-MSCs on improving the prognostic outcome.…”

“…Of importance was that the result of the present study identified that early administration was better than late administration of iPS-MSCs on improving the prognostic outcome. Accordingly, the result of this study was consistent with those from our previous studies [40,41]. Of particularly important finding was that combined iPS-MSCs and ciprofloxacin was superior to either one alone for protecting the kidney organ and improving the prognostic outcome, highlighting that this strategic management may serve as a therapeutic protection for those severe sepsis patients complicated with major organ failure and are refractory to conventional treatment.…”

Umbilical cord‐derived MSC and hyperbaric oxygen therapy effectively protected the brain in rat after acute intracerebral haemorrhage

“…We proposed the therapeutic regimen of the multiple dosages of HUCDMSCs (ie like the regimen of antibiotics to be utilized for treatment the bacterial‐induced sepsis in our daily clinical practice) could be the key to success for remarkable preservation of the brain architecture and neurological function. Interestingly, our previous 36 and recent 37 studies have shown that early and multiple dosages of stem cell administration was the crucial role on reducing the post‐heart transplant acute rejection 36 and preservation of the neurological function after acute ischaemic stroke 37 in rodent. In this way, the results of the present study, in addition to being comparable with the findings of our previous 36 and recent 37 studies, highlight that this regimen could be seriously considered in our future stem cell therapy for the patients.…”

Combined Human Umbilical Cord-Derived Stem Cell and Hyperbaric Oxygen Therapy Effectively Preserved the Neurological Function and Brain Architecture in Rat After Acute Intracerebral Hemorrhage

“…We proposed the therapeutic regimen of the multiple dosages of HUCDMSCs (i.e., like the regimen of antibiotics to be utilized for treatment the bacterial-induced sepsis in our daily clinical practice) could be the key to success for remarkable preservation the brain architecture and neurological function. Interestingly, our previous [36] and recent [37] studies have shown that early and multiple dosages of stem cell administration was the crucial role on reducing the post-heart transplant acute rejection [37] and preservation of the neurological function after acute ischemic stroke [38] in rodent. In this way, the results of the present study, in addition to being comparable with the ndings of our previous [36] and recent [37] studies, highlight that this regimen could be seriously considered in our future stem cell therapy for the patients.…”