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

Abstract

This study tested the hypothesis that combined therapy with human umbilical cord‐derived mesenchymal stem cells (HUCDMSCs) and hyperbaric oxygen (HBO) was superior to either one on preserving neurological function and reducing brain haemorrhagic volume (BHV) in rat after acute intracerebral haemorrhage (ICH) induced by intracranial injection of collagenase. Adult male SD rats (n = 30) were equally divided into group 1 (sham‐operated control), group 2 (ICH), group 3 (ICH +HUCDMSCs/1.2 × 106 cells/intravenous injection at 3h and days 1 and 2 after ICH), group 4 (ICH +HBO/at 3 hours and days 1 and 2 after ICH) and group 5 (ICH +HUCDMSCs‐HBO), and killed by day 28 after ICH. By day 1, the neurological function was significantly impaired in groups 2‐5 than in group 1 (P < .001), but it did not differ among groups 2 to 5. By days 7, 14 and 28, the integrity of neurological function was highest in group 1, lowest in group 2 and significantly progressively improved from groups 3 to 5 (all P < .001). By day 28, the BHV was lowest in group 1, highest in group 2 and significantly lower in group 5 than in groups 3/4 (all P < .0001). The protein expressions of inflammation (HMGB1/TLR‐2/TLR‐4/MyD88/TRAF6/p‐NF‐κB/IFN‐γ/IL‐1ß/TNF‐α), oxidative stress/autophagy (NOX‐1/NOX‐2/oxidized protein/ratio of LC3B‐II/LC3B‐I) and apoptosis (cleaved‐capspase3/PARP), and cellular expressions of inflammation (CD14+, F4/80+) in brain tissues exhibited an identical pattern, whereas cellular levels of angiogenesis (CD31+/vWF+/small‐vessel number) and number of neurons (NeuN+) exhibited an opposite pattern of BHV among the groups (all P < .0001). These results indicate that combined HUCDMSC‐HBO therapy offered better outcomes after rat ICH.

Dose-dependent benefits of iron-magnetic nanoparticle-coated human umbilical-derived mesenchymal stem cell treatment in rat intracranial hemorrhage model

“…An essential finding in the present study was that the inflammation and circulation and oxidative stress biomarkers in the brain tissue were found to be substantially increased, followed by remarkably increased in the apoptotic, fibrotic, DNA-damaged and mitochondrial damage biomarkers in hemorrhagic brain tissues. In this way, our findings, in addition to corroborating with the findings of the previous studies [ 25 – 27 , 30 , 31 , 33 , 34 ], could, at least in part, explain why the BHV was markedly increased in ICH animals. Paramount importance was that these molecular-cellular perturbations were notably reversed by one dose and more notably reversed by two consecutive doses of cell therapy.…”

“…Numerous studies have revealed that tissue/organ in circumstances of ischemia and necrosis always drew forth of large amount of inflammation and oxidative stress, which in turn, stimulated cell stress signaling, resulting in DNA/mitochondrial damage and cell apoptosis and death [ 25 – 27 , 30 , 31 , 33 , 34 ]. An essential finding in the present study was that the inflammation and circulation and oxidative stress biomarkers in the brain tissue were found to be substantially increased, followed by remarkably increased in the apoptotic, fibrotic, DNA-damaged and mitochondrial damage biomarkers in hemorrhagic brain tissues.…”

“…Pathogen-free, adult male Sprague Dawley (SD) rats, 300–320 g (Charles River Technology, BioLASCO Taiwan Co. Ltd., Taiwan) were utilized in the present study. The procedure and protocol were based on our recent report [ 25 ]. In detail, the stereotactic apparatus was set up and animals were anesthetized by inhalational 2.0% isoflurane, placed in a prone position on a warming pad at 37 °C for acute ICH induction.…”

Intrarenal arterial administration of human umbilical cord-derived mesenchymal stem cells effectively preserved the residual renal function of diabetic kidney disease in rat

“…Abundant data have shown that mesenchymal stem cells (MSCs) therapy effectively protected the organs from different disease entities mainly through inhibiting the inflammation and innate and adaptive immunity through down-regulating immunogenicity [ 32 – 37 ]. Our recent phase I clinical trial also demonstrated that human umbilical cord-derived mesenchymal stem cells (HUCDMSCs) therapy was safe and life-saving for moderate–severe acute respiratory distress syndrome (ARDS) patients [ 38 ].…”

Application of stem cells and exosomes in the treatment of intracerebral hemorrhage: an update

“…A recently published study that combined umbilical cord-derived MSCs with hyperbaric oxygen to treat ICH in mice reported that combined treatment was significantly better than a single treatment [ 77 ]. Although they believe that this is inseparable from the low immunogenicity of hUC-MSCs and the effects of hyperbaric oxygen therapy on improving MSCs levels, the specific molecular mechanism remains to be elucidated [ 110 , 111 ]. WJ-derived mesenchymal stromal/stem cells (WJ-MSCs) are hUC-MSCs with primitive stemness properties.…”