Lim Hyosun, Park Sun Hwa, Kim Sung Won, Cho Kyung-Ok
Department of Pharmacology, Department of Biomedicine & Health Sciences, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Int Neurourol J. 2018 Oct;22(Suppl 3):S131-138. doi: 10.5213/inj.1836220.110. Epub 2018 Oct 31.
Mesenchymal stem cells (MSCs) have demonstrated great promises for the treatment of ischemic stroke. Previously, we identified a new source of MSCs located in the inferior turbinate. We investigated therapeutic potentials of human turbinate- derived mesenchymal stem cells (hTMSCs) in ischemic stroke.
Ischemic stroke was induced by the intraluminal occlusion of middle cerebral artery (MCAo) for 50 minutes in rats. At one day after MCAo, hTMSCs, adipose tissue-derived MSCs (AdMSCs), or phosphate buffered saline (PBS) were transplanted into the striatum. Functional recovery was assessed by repeating behavioral tests including modified neurologic severity score and corner test. At 14 days after MCAo, brains were stained with hematoxylin and eosin (H&E) for measuring infarct volume. The survival of grafted MSCs was evaluated by immunohistochemistry to human nuclei (hNU). Immunohistochemistry with anti-doublecortin (anti-DCX) was performed to assess hippocampal neurogenesis.
Transplantation of hTMSCs following MCAo showed improvements of neurologic function, which was comparable with that of AdMSCs. H&E staining showed no difference in infarct volume among 3 groups. Regarding the survival of grafted MSCs, the number of hNU-expressing cells was not different between hTMSCs- and AdMSCs-treated groups. Finally, hTMSCs increased the number of subgranular DCX-positive cells compared to PBS-treated controls, without affecting hilar ectopic migration of newborn neurons.
hTMSCs could improve functional recovery following ischemic stroke, of which efficacy was similar to AdMSCs. Although hTMSCs showed comparable infarct size and survival of grafted MSCs, transplantation of hTMSCs could upregulate subgranular neurogenesis with no impact on ectopically migrating newborn neurons.
间充质干细胞（MSCs）在缺血性脑卒中治疗方面展现出巨大潜力。此前，我们发现了位于下鼻甲的一种新的MSCs来源。我们研究了人鼻甲来源的间充质干细胞（hTMSCs）在缺血性脑卒中中的治疗潜力。
通过大脑中动脉腔内闭塞（MCAo）50分钟诱导大鼠缺血性脑卒中。MCAo术后一天，将hTMSCs、脂肪组织来源的MSCs（AdMSCs）或磷酸盐缓冲盐水（PBS）移植到纹状体。通过重复行为测试评估功能恢复情况，包括改良神经功能缺损评分和转角试验。MCAo术后14天，用苏木精和伊红（H&E）对大脑进行染色以测量梗死体积。通过人细胞核（hNU）免疫组化评估移植MSCs的存活情况。进行抗双皮质素（抗DCX）免疫组化以评估海马神经发生。
MCAo后移植hTMSCs显示神经功能改善，与AdMSCs相当。H&E染色显示三组梗死体积无差异。关于移植MSCs的存活情况，hTMSCs治疗组和AdMSCs治疗组中表达hNU的细胞数量没有差异。最后，与PBS处理的对照组相比，hTMSCs增加了颗粒下DCX阳性细胞的数量，且不影响新生神经元的海马旁异位迁移。
hTMSCs可改善缺血性脑卒中后的功能恢复，其疗效与AdMSCs相似。尽管hTMSCs在梗死面积和移植MSCs的存活方面表现相当，但移植hTMSCs可上调颗粒下神经发生，且不影响异位迁移的新生神经元。
