Oligodendrocytes in human induced pluripotent stem cell-derived cortical grafts remyelinate adult rat and human cortical neurons

被引:6
|
作者
Martinez-Curiel, Raquel [1 ]
Jansson, Linda [1 ]
Tsupykov, Oleg [2 ,3 ]
Avaliani, Natalia [4 ,5 ]
Aretio-Medina, Constanza [1 ]
Hidalgo, Isabel [6 ]
Monni, Emanuela [4 ,5 ]
Bengzon, Johan
Skibo, Galyna [2 ,3 ]
Lindvall, Olle [1 ]
Kokaja, Zaal [1 ]
Palma-Tortosa, Sara [1 ]
机构
[1] Lund Univ, Lund Stem Cell Ctr, Lab Stem Cells & Restorat Neurol, S-22184 Lund, Sweden
[2] Bogomoletz Inst Physiol, Dept Cytol, Kiev, Ukraine
[3] Strazhesko Natl Sci Ctr Cardiol Clin & Regenerat M, Inst Genet & Regenerat Med, Kiev, Ukraine
[4] Lund Univ, Lund Stem Cell Ctr, S-22184 Lund, Sweden
[5] Lund Univ, Wallenberg Ctr Mol Med, Lund Stem Cell Ctr, Div Mol Hematol, S-22184 Lund, Sweden
[6] Univ Hosp, Dept Clin Sci Lund, Div Neurosurg, S-22184 Lund, Sweden
来源
STEM CELL REPORTS | 2023年 / 18卷 / 08期
关键词
SPINAL-CORD-INJURY; PROGENITOR CELLS; MOUSE MODEL; BRAIN; GENERATION; MYELINATE; RECOVERY; RESCUE;
D O I
10.1016/j.stemcr.2023.04.010
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Neuronal loss and axonal demyelination underlie long-term functional impairments in patients affected by brain disorders such as ischemic stroke. Stem cell-based approaches reconstructing and remyelinating brain neural circuitry, leading to recovery, are highly war-ranted. Here, we demonstrate the in vitro and in vivo production of myelinating oligodendrocytes from a human induced pluripotent stem cell (iPSC)-derived long-term neuroepithelial stem (lt-NES) cell line, which also gives rise to neurons with the capacity to integrate into stroke-injured, adult rat cortical networks. Most importantly, the generated oligodendrocytes survive and form myelin-ensheathing hu-man axons in the host tissue after grafting onto adult human cortical organotypic cultures. This lt-NES cell line is the first human stem cell source that, after intracerebral delivery, can repair both injured neural circuitries and demyelinated axons. Our findings provide support-ive evidence for the potential future use of human iPSC-derived cell lines to promote effective clinical recovery following brain injuries.
引用
收藏
页码:1643 / 1656
页数:14
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