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

• Published in: Journal of cellular and molecular medicine Vol. 25; no. 12; pp. 5640 - 5654
• Main Authors: Yip, Hon‐Kan, Lin, Kun‐Chen, Sung, Pei‐Hsun, Chiang, John Y., Yin, Tsung‐Cheng, Wu, Re‐Wen, Chen, Kuan‐Hung
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.06.2021; John Wiley and Sons Inc
• Subjects: Angiogenesis; Apoptosis; Autophagy; CD14 antigen; Collagen; Collagenase; Hemorrhage; HMGB1 protein; Homeostasis; hyperbaric oxygen; Hyperbaric oxygen therapy; Hypoxia; Inflammation; Injection; Interferon; intracerebral haemorrhage; Intravenous administration; Laboratory animals; Mesenchymal stem cells; Mesenchyme; MyD88 protein; neurological function; Original; Oxidative stress; Oxygen therapy; Phagocytosis; Stem cell transplantation; Stem cells; Stroke; TRAF6 protein; Traumatic brain injury; Tumor necrosis factor; Umbilical cord; United States > US; Taiwan; intracerebral haemorrhage; neurological function; hyperbaric oxygen; mesenchymal stem cells
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.16577

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.