Transplanted microvascular endothelial cells promote oligodendrocyte precursor cell survival in ischemic demyelinating lesions

Iijima, Keiya; Kurachi, Masayoshi; Shibasaki, Kazuo; Naruse, Masae; Puentes, Sandra; Imai, Hideki; Yoshimoto, Yuhei; Murakami, Masahiko; Ishizaki, Yasuki

doi:10.1111/jnc.13262

Cited by 16 publications

(21 citation statements)

References 33 publications

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“…We confirmed our previous study reporting that MVEC-CM reduced apoptotic cell death of OPCs [ 4 ], and found that MVEC-CM promoted their motility ( Fig 1 ). ECs are active and dynamic cells producing various biologically active molecules in response to various stimuli.…”

Section: Discussionsupporting

confidence: 92%

“…In contrast, in serum-free medium (control) and EV-dep-MVEC-CM, many OPCs died with the typical morphological features of apoptosis including pyknotic nuclei. As we reported previously, MVEC-CM had no apparent effect on OPC differentiation [ 4 ].…”

Section: Resultssupporting

confidence: 58%

“…We previously showed that transplantation of brain microvascular endothelial cells (MVECs) greatly stimulated remyelination in the white matter infarct of the internal capsule (IC) induced by endothelin-1 (ET-1) injection and improved the behavioral outcome [ 3 ]. We also showed that MVEC transplantation reduced apoptotic death of oligodendrocyte precursor cells (OPCs) and that the conditioned medium (CM) from cultured MVECs (MVEC-CM) inhibited apoptosis of cultured OPCs [ 4 ]. These results indicate that MVECs produce and release some factors with a pro-survival activity on OPCs, and these factors might contribute to the recovery of the white matter infarct.…”

Section: Introductionmentioning

confidence: 99%

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Extracellular Vesicles from Vascular Endothelial Cells Promote Survival, Proliferation and Motility of Oligodendrocyte Precursor Cells

2016

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We previously examined the effect of brain microvascular endothelial cell (MVEC) transplantation on rat white matter infarction, and found that MVEC transplantation promoted remyelination of demyelinated axons in the infarct region and reduced apoptotic death of oligodendrocyte precursor cells (OPCs). We also found that the conditioned medium (CM) from cultured MVECs inhibited apoptosis of cultured OPCs. In this study, we examined contribution of extracellular vesicles (EVs) contained in the CM to its inhibitory effect on OPC apoptosis. Removal of EVs from the CM by ultracentrifugation reduced its inhibitory effect on OPC apoptosis. To confirm whether EVs derived from MVECs are taken up by cultured OPCs, we labeled EVs with PKH67, a fluorescent dye, and added them to OPC cultures. Many vesicular structures labeled with PKH67 were found within OPCs immediately after their addition. Next we examined the effect of MVEC-derived EVs on OPC behaviors. After 2 days in culture with EVs, there was significantly less pyknotic and more BrdU-positive OPCs when compared to control. We also examined the effect of EVs on motility of OPCs. OPCs migrated longer in the presence of EVs when compared to control. To examine whether these effects on cultured OPCs are shared by EVs from endothelial cells, we prepared EVs from conditioned media of several types of endothelial cells, and tested their effects on cultured OPCs. EVs from all types of endothelial cells we examined reduced apoptosis of OPCs and promoted their motility. Identification of the molecules contained in EVs from endothelial cells may prove helpful for establishment of effective therapies for demyelinating diseases.

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Section: Discussionsupporting

confidence: 92%

Section: Resultssupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

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Extracellular Vesicles from Vascular Endothelial Cells Promote Survival, Proliferation and Motility of Oligodendrocyte Precursor Cells

2016

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“…We previously reported that MVEC transplantation increased the number of OPCs by inhibiting apoptotic death in the rat model of white matter infarct (Iijima et al, ). We also reported that EVs secreted from endothelial cells promoted survival, proliferation and motility of cultured OPCs (Kurachi et al, ).…”

Section: Discussionmentioning

confidence: 97%

Transplantation of iPS‐derived vascular endothelial cells improves white matter ischemic damage

Kurachi

Shimauchi-Ohtaki

et al. 2020

Journal of Neurochemistry

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White matter infarct induces demyelination and brain dysfunction. We previously reported that transplantation of brain microvascular endothelial cells improved the behavioral outcome and promoted remyelination by increasing the number of oligodendrocyte precursor cells in the rat model of white matter infarct. In this study, we investigated the effects of transplantation of vascular endothelial cells generated from human induced pluripotent stem cells (iPSCs) on the rat model of white matter infarct. Seven days after induction of ischemic demyelinating lesion by injection of endothelin‐1 into the internal capsule of a rat brain, iPSC‐derived vascular endothelial cells (iVECs) were transplanted into the site of demyelination. The majority of iVECs transplanted into the internal capsule survived for 14 days after transplantation when traced by immunohistochemistry for a human cytoplasmic protein. iVEC transplantation significantly recovered hind limb rotation angle as compared to human iPSC or rat meningeal cell transplantation when evaluated using footprint test. Fourteen days after iVEC transplantation, the infarct area remarkably decreased as compared to that just before the transplantation when evaluated using magnetic resonance imaging or luxol fast blue staining, and remyelination was promoted dramatically in the infarct when assessed using luxol fast blue staining. Transplantation of iVECs increased the number of oligodendrocyte lineage cells and suppressed the inflammatory response and reactive astrocytogenesis. These results suggest that iVEC transplantation may prove useful in treatment for white matter infarct.

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“…Guo et al [ 54 ] demonstrated that secretion of brain-derived neurotrophic factor (BDNF) by CECs was vital for neuroprotection. In addition, soluble factors secreted by CECs were found to enhance the proliferation of oligodendrocyte progenitor cells (OPC); which are precursors of oligodendrocytes as well decrease apoptotic OPC death in vitro [ 55 , 56 ]. Furthermore, extracellular vesicles derived from rat brain CECs were shown to have a role in promoting OPC survival, proliferation and motility in a dose-dependent manner [ 57 ].…”

Section: Background: the Blood–brain Barrier As Part Of The Neurovascmentioning

confidence: 99%

Brain vascular heterogeneity: implications for disease pathogenesis and design of in vitro blood–brain barrier models

Noumbissi

Galasso

Stins

2018

Fluids Barriers CNS

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The vertebrate blood–brain barrier (BBB) is composed of cerebral microvascular endothelial cells (CEC). The BBB acts as a semi-permeable cellular interface that tightly regulates bidirectional molecular transport between blood and the brain parenchyma in order to maintain cerebral homeostasis. The CEC phenotype is regulated by a variety of factors, including cells in its immediate environment and within functional neurovascular units. The cellular composition of the brain parenchyma surrounding the CEC varies between different brain regions; this difference is clearly visible in grey versus white matter. In this review, we discuss evidence for the existence of brain vascular heterogeneity, focusing on differences between the vessels of the grey and white matter. The region-specific differences in the vasculature of the brain are reflective of specific functions of those particular brain areas. This BBB-endothelial heterogeneity may have implications for the course of pathogenesis of cerebrovascular diseases and neurological disorders involving vascular activation and dysfunction. This heterogeneity should be taken into account when developing BBB-neuro-disease models representative of specific brain areas.

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Transplanted microvascular endothelial cells promote oligodendrocyte precursor cell survival in ischemic demyelinating lesions

Cited by 16 publications

References 33 publications

Extracellular Vesicles from Vascular Endothelial Cells Promote Survival, Proliferation and Motility of Oligodendrocyte Precursor Cells

Extracellular Vesicles from Vascular Endothelial Cells Promote Survival, Proliferation and Motility of Oligodendrocyte Precursor Cells

Transplantation of iPS‐derived vascular endothelial cells improves white matter ischemic damage

Brain vascular heterogeneity: implications for disease pathogenesis and design of in vitro blood–brain barrier models

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