Grafted human pluripotent stem cell‐derived cortical neurons integrate into adult human cortical neural circuitry

Abstract Several neurodegenerative diseases cause loss of cortical neurons, leading to sensory, motor, and cognitive impairments. Studies in different animal models have raised the possibility that transplantation of human cortical neuronal progenitors, generated from pluripotent stem cells, might b...
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Autor*in:	Marita Grønning Hansen [verfasserIn] Cecilia Laterza [verfasserIn] Sara Palma‐Tortosa [verfasserIn] Giedre Kvist [verfasserIn] Emanuela Monni [verfasserIn] Oleg Tsupykov [verfasserIn] Daniel Tornero [verfasserIn] Naomi Uoshima [verfasserIn] Jordi Soriano [verfasserIn] Johan Bengzon [verfasserIn] Gianvito Martino [verfasserIn] Galyna Skibo [verfasserIn] Olle Lindvall [verfasserIn] Zaal Kokaia [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	cerebral cortex human iPS cells neural circuitry regeneration transplantation

Übergeordnetes Werk:	In: Stem Cells Translational Medicine - Oxford University Press, 2017, 9(2020), 11, Seite 1365-1377
Übergeordnetes Werk:	volume:9 ; year:2020 ; number:11 ; pages:1365-1377

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.1002/sctm.20-0134

Katalog-ID:	DOAJ018341918

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520			\|a Abstract Several neurodegenerative diseases cause loss of cortical neurons, leading to sensory, motor, and cognitive impairments. Studies in different animal models have raised the possibility that transplantation of human cortical neuronal progenitors, generated from pluripotent stem cells, might be developed into a novel therapeutic strategy for disorders affecting cerebral cortex. For example, we have shown that human long‐term neuroepithelial‐like stem (lt‐NES) cell‐derived cortical neurons, produced from induced pluripotent stem cells and transplanted into stroke‐injured adult rat cortex, improve neurological deficits and establish both afferent and efferent morphological and functional connections with host cortical neurons. So far, all studies with human pluripotent stem cell‐derived neurons have been carried out using xenotransplantation in animal models. Whether these neurons can integrate also into adult human brain circuitry is unknown. Here, we show that cortically fated lt‐NES cells, which are able to form functional synaptic networks in cell culture, differentiate to mature, layer‐specific cortical neurons when transplanted ex vivo onto organotypic cultures of adult human cortex. The grafted neurons are functional and establish both afferent and efferent synapses with adult human cortical neurons in the slices as evidenced by immuno‐electron microscopy, rabies virus retrograde monosynaptic tracing, and whole‐cell patch‐clamp recordings. Our findings provide the first evidence that pluripotent stem cell‐derived neurons can integrate into adult host neural networks also in a human‐to‐human grafting situation, thereby supporting their potential future clinical use to promote recovery by neuronal replacement in the patient's diseased brain.
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allfields	10.1002/sctm.20-0134 doi (DE-627)DOAJ018341918 (DE-599)DOAJ181e28f31b85430e89ba814c4933f424 DE-627 ger DE-627 rakwb eng R5-920 QH573-671 Marita Grønning Hansen verfasserin aut Grafted human pluripotent stem cell‐derived cortical neurons integrate into adult human cortical neural circuitry 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Several neurodegenerative diseases cause loss of cortical neurons, leading to sensory, motor, and cognitive impairments. Studies in different animal models have raised the possibility that transplantation of human cortical neuronal progenitors, generated from pluripotent stem cells, might be developed into a novel therapeutic strategy for disorders affecting cerebral cortex. For example, we have shown that human long‐term neuroepithelial‐like stem (lt‐NES) cell‐derived cortical neurons, produced from induced pluripotent stem cells and transplanted into stroke‐injured adult rat cortex, improve neurological deficits and establish both afferent and efferent morphological and functional connections with host cortical neurons. So far, all studies with human pluripotent stem cell‐derived neurons have been carried out using xenotransplantation in animal models. Whether these neurons can integrate also into adult human brain circuitry is unknown. Here, we show that cortically fated lt‐NES cells, which are able to form functional synaptic networks in cell culture, differentiate to mature, layer‐specific cortical neurons when transplanted ex vivo onto organotypic cultures of adult human cortex. The grafted neurons are functional and establish both afferent and efferent synapses with adult human cortical neurons in the slices as evidenced by immuno‐electron microscopy, rabies virus retrograde monosynaptic tracing, and whole‐cell patch‐clamp recordings. Our findings provide the first evidence that pluripotent stem cell‐derived neurons can integrate into adult host neural networks also in a human‐to‐human grafting situation, thereby supporting their potential future clinical use to promote recovery by neuronal replacement in the patient's diseased brain. cerebral cortex human iPS cells neural circuitry regeneration transplantation Medicine (General) Cytology Cecilia Laterza verfasserin aut Sara Palma‐Tortosa verfasserin aut Giedre Kvist verfasserin aut Emanuela Monni verfasserin aut Oleg Tsupykov verfasserin aut Daniel Tornero verfasserin aut Naomi Uoshima verfasserin aut Jordi Soriano verfasserin aut Johan Bengzon verfasserin aut Gianvito Martino verfasserin aut Galyna Skibo verfasserin aut Olle Lindvall verfasserin aut Zaal Kokaia verfasserin aut In Stem Cells Translational Medicine Oxford University Press, 2017 9(2020), 11, Seite 1365-1377 (DE-627)680320539 (DE-600)2642270-0 21576580 nnns volume:9 year:2020 number:11 pages:1365-1377 https://doi.org/10.1002/sctm.20-0134 kostenfrei https://doaj.org/article/181e28f31b85430e89ba814c4933f424 kostenfrei https://doi.org/10.1002/sctm.20-0134 kostenfrei https://doaj.org/toc/2157-6564 Journal toc kostenfrei https://doaj.org/toc/2157-6580 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2020 11 1365-1377
spelling	10.1002/sctm.20-0134 doi (DE-627)DOAJ018341918 (DE-599)DOAJ181e28f31b85430e89ba814c4933f424 DE-627 ger DE-627 rakwb eng R5-920 QH573-671 Marita Grønning Hansen verfasserin aut Grafted human pluripotent stem cell‐derived cortical neurons integrate into adult human cortical neural circuitry 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Several neurodegenerative diseases cause loss of cortical neurons, leading to sensory, motor, and cognitive impairments. Studies in different animal models have raised the possibility that transplantation of human cortical neuronal progenitors, generated from pluripotent stem cells, might be developed into a novel therapeutic strategy for disorders affecting cerebral cortex. For example, we have shown that human long‐term neuroepithelial‐like stem (lt‐NES) cell‐derived cortical neurons, produced from induced pluripotent stem cells and transplanted into stroke‐injured adult rat cortex, improve neurological deficits and establish both afferent and efferent morphological and functional connections with host cortical neurons. So far, all studies with human pluripotent stem cell‐derived neurons have been carried out using xenotransplantation in animal models. Whether these neurons can integrate also into adult human brain circuitry is unknown. Here, we show that cortically fated lt‐NES cells, which are able to form functional synaptic networks in cell culture, differentiate to mature, layer‐specific cortical neurons when transplanted ex vivo onto organotypic cultures of adult human cortex. The grafted neurons are functional and establish both afferent and efferent synapses with adult human cortical neurons in the slices as evidenced by immuno‐electron microscopy, rabies virus retrograde monosynaptic tracing, and whole‐cell patch‐clamp recordings. Our findings provide the first evidence that pluripotent stem cell‐derived neurons can integrate into adult host neural networks also in a human‐to‐human grafting situation, thereby supporting their potential future clinical use to promote recovery by neuronal replacement in the patient's diseased brain. cerebral cortex human iPS cells neural circuitry regeneration transplantation Medicine (General) Cytology Cecilia Laterza verfasserin aut Sara Palma‐Tortosa verfasserin aut Giedre Kvist verfasserin aut Emanuela Monni verfasserin aut Oleg Tsupykov verfasserin aut Daniel Tornero verfasserin aut Naomi Uoshima verfasserin aut Jordi Soriano verfasserin aut Johan Bengzon verfasserin aut Gianvito Martino verfasserin aut Galyna Skibo verfasserin aut Olle Lindvall verfasserin aut Zaal Kokaia verfasserin aut In Stem Cells Translational Medicine Oxford University Press, 2017 9(2020), 11, Seite 1365-1377 (DE-627)680320539 (DE-600)2642270-0 21576580 nnns volume:9 year:2020 number:11 pages:1365-1377 https://doi.org/10.1002/sctm.20-0134 kostenfrei https://doaj.org/article/181e28f31b85430e89ba814c4933f424 kostenfrei https://doi.org/10.1002/sctm.20-0134 kostenfrei https://doaj.org/toc/2157-6564 Journal toc kostenfrei https://doaj.org/toc/2157-6580 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2020 11 1365-1377
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allfieldsSound	10.1002/sctm.20-0134 doi (DE-627)DOAJ018341918 (DE-599)DOAJ181e28f31b85430e89ba814c4933f424 DE-627 ger DE-627 rakwb eng R5-920 QH573-671 Marita Grønning Hansen verfasserin aut Grafted human pluripotent stem cell‐derived cortical neurons integrate into adult human cortical neural circuitry 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Several neurodegenerative diseases cause loss of cortical neurons, leading to sensory, motor, and cognitive impairments. Studies in different animal models have raised the possibility that transplantation of human cortical neuronal progenitors, generated from pluripotent stem cells, might be developed into a novel therapeutic strategy for disorders affecting cerebral cortex. For example, we have shown that human long‐term neuroepithelial‐like stem (lt‐NES) cell‐derived cortical neurons, produced from induced pluripotent stem cells and transplanted into stroke‐injured adult rat cortex, improve neurological deficits and establish both afferent and efferent morphological and functional connections with host cortical neurons. So far, all studies with human pluripotent stem cell‐derived neurons have been carried out using xenotransplantation in animal models. Whether these neurons can integrate also into adult human brain circuitry is unknown. Here, we show that cortically fated lt‐NES cells, which are able to form functional synaptic networks in cell culture, differentiate to mature, layer‐specific cortical neurons when transplanted ex vivo onto organotypic cultures of adult human cortex. The grafted neurons are functional and establish both afferent and efferent synapses with adult human cortical neurons in the slices as evidenced by immuno‐electron microscopy, rabies virus retrograde monosynaptic tracing, and whole‐cell patch‐clamp recordings. Our findings provide the first evidence that pluripotent stem cell‐derived neurons can integrate into adult host neural networks also in a human‐to‐human grafting situation, thereby supporting their potential future clinical use to promote recovery by neuronal replacement in the patient's diseased brain. cerebral cortex human iPS cells neural circuitry regeneration transplantation Medicine (General) Cytology Cecilia Laterza verfasserin aut Sara Palma‐Tortosa verfasserin aut Giedre Kvist verfasserin aut Emanuela Monni verfasserin aut Oleg Tsupykov verfasserin aut Daniel Tornero verfasserin aut Naomi Uoshima verfasserin aut Jordi Soriano verfasserin aut Johan Bengzon verfasserin aut Gianvito Martino verfasserin aut Galyna Skibo verfasserin aut Olle Lindvall verfasserin aut Zaal Kokaia verfasserin aut In Stem Cells Translational Medicine Oxford University Press, 2017 9(2020), 11, Seite 1365-1377 (DE-627)680320539 (DE-600)2642270-0 21576580 nnns volume:9 year:2020 number:11 pages:1365-1377 https://doi.org/10.1002/sctm.20-0134 kostenfrei https://doaj.org/article/181e28f31b85430e89ba814c4933f424 kostenfrei https://doi.org/10.1002/sctm.20-0134 kostenfrei https://doaj.org/toc/2157-6564 Journal toc kostenfrei https://doaj.org/toc/2157-6580 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2020 11 1365-1377
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authorswithroles_txt_mv	Marita Grønning Hansen @@aut@@ Cecilia Laterza @@aut@@ Sara Palma‐Tortosa @@aut@@ Giedre Kvist @@aut@@ Emanuela Monni @@aut@@ Oleg Tsupykov @@aut@@ Daniel Tornero @@aut@@ Naomi Uoshima @@aut@@ Jordi Soriano @@aut@@ Johan Bengzon @@aut@@ Gianvito Martino @@aut@@ Galyna Skibo @@aut@@ Olle Lindvall @@aut@@ Zaal Kokaia @@aut@@
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callnumber-first	R - Medicine
author	Marita Grønning Hansen
spellingShingle	Marita Grønning Hansen misc R5-920 misc QH573-671 misc cerebral cortex misc human misc iPS cells misc neural circuitry misc regeneration misc transplantation misc Medicine (General) misc Cytology Grafted human pluripotent stem cell‐derived cortical neurons integrate into adult human cortical neural circuitry
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topic_title	R5-920 QH573-671 Grafted human pluripotent stem cell‐derived cortical neurons integrate into adult human cortical neural circuitry cerebral cortex human iPS cells neural circuitry regeneration transplantation
topic	misc R5-920 misc QH573-671 misc cerebral cortex misc human misc iPS cells misc neural circuitry misc regeneration misc transplantation misc Medicine (General) misc Cytology
topic_unstemmed	misc R5-920 misc QH573-671 misc cerebral cortex misc human misc iPS cells misc neural circuitry misc regeneration misc transplantation misc Medicine (General) misc Cytology
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title	Grafted human pluripotent stem cell‐derived cortical neurons integrate into adult human cortical neural circuitry
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title_full	Grafted human pluripotent stem cell‐derived cortical neurons integrate into adult human cortical neural circuitry
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title_sort	grafted human pluripotent stem cell‐derived cortical neurons integrate into adult human cortical neural circuitry
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title_auth	Grafted human pluripotent stem cell‐derived cortical neurons integrate into adult human cortical neural circuitry
abstract	Abstract Several neurodegenerative diseases cause loss of cortical neurons, leading to sensory, motor, and cognitive impairments. Studies in different animal models have raised the possibility that transplantation of human cortical neuronal progenitors, generated from pluripotent stem cells, might be developed into a novel therapeutic strategy for disorders affecting cerebral cortex. For example, we have shown that human long‐term neuroepithelial‐like stem (lt‐NES) cell‐derived cortical neurons, produced from induced pluripotent stem cells and transplanted into stroke‐injured adult rat cortex, improve neurological deficits and establish both afferent and efferent morphological and functional connections with host cortical neurons. So far, all studies with human pluripotent stem cell‐derived neurons have been carried out using xenotransplantation in animal models. Whether these neurons can integrate also into adult human brain circuitry is unknown. Here, we show that cortically fated lt‐NES cells, which are able to form functional synaptic networks in cell culture, differentiate to mature, layer‐specific cortical neurons when transplanted ex vivo onto organotypic cultures of adult human cortex. The grafted neurons are functional and establish both afferent and efferent synapses with adult human cortical neurons in the slices as evidenced by immuno‐electron microscopy, rabies virus retrograde monosynaptic tracing, and whole‐cell patch‐clamp recordings. Our findings provide the first evidence that pluripotent stem cell‐derived neurons can integrate into adult host neural networks also in a human‐to‐human grafting situation, thereby supporting their potential future clinical use to promote recovery by neuronal replacement in the patient's diseased brain.
abstractGer	Abstract Several neurodegenerative diseases cause loss of cortical neurons, leading to sensory, motor, and cognitive impairments. Studies in different animal models have raised the possibility that transplantation of human cortical neuronal progenitors, generated from pluripotent stem cells, might be developed into a novel therapeutic strategy for disorders affecting cerebral cortex. For example, we have shown that human long‐term neuroepithelial‐like stem (lt‐NES) cell‐derived cortical neurons, produced from induced pluripotent stem cells and transplanted into stroke‐injured adult rat cortex, improve neurological deficits and establish both afferent and efferent morphological and functional connections with host cortical neurons. So far, all studies with human pluripotent stem cell‐derived neurons have been carried out using xenotransplantation in animal models. Whether these neurons can integrate also into adult human brain circuitry is unknown. Here, we show that cortically fated lt‐NES cells, which are able to form functional synaptic networks in cell culture, differentiate to mature, layer‐specific cortical neurons when transplanted ex vivo onto organotypic cultures of adult human cortex. The grafted neurons are functional and establish both afferent and efferent synapses with adult human cortical neurons in the slices as evidenced by immuno‐electron microscopy, rabies virus retrograde monosynaptic tracing, and whole‐cell patch‐clamp recordings. Our findings provide the first evidence that pluripotent stem cell‐derived neurons can integrate into adult host neural networks also in a human‐to‐human grafting situation, thereby supporting their potential future clinical use to promote recovery by neuronal replacement in the patient's diseased brain.
abstract_unstemmed	Abstract Several neurodegenerative diseases cause loss of cortical neurons, leading to sensory, motor, and cognitive impairments. Studies in different animal models have raised the possibility that transplantation of human cortical neuronal progenitors, generated from pluripotent stem cells, might be developed into a novel therapeutic strategy for disorders affecting cerebral cortex. For example, we have shown that human long‐term neuroepithelial‐like stem (lt‐NES) cell‐derived cortical neurons, produced from induced pluripotent stem cells and transplanted into stroke‐injured adult rat cortex, improve neurological deficits and establish both afferent and efferent morphological and functional connections with host cortical neurons. So far, all studies with human pluripotent stem cell‐derived neurons have been carried out using xenotransplantation in animal models. Whether these neurons can integrate also into adult human brain circuitry is unknown. Here, we show that cortically fated lt‐NES cells, which are able to form functional synaptic networks in cell culture, differentiate to mature, layer‐specific cortical neurons when transplanted ex vivo onto organotypic cultures of adult human cortex. The grafted neurons are functional and establish both afferent and efferent synapses with adult human cortical neurons in the slices as evidenced by immuno‐electron microscopy, rabies virus retrograde monosynaptic tracing, and whole‐cell patch‐clamp recordings. Our findings provide the first evidence that pluripotent stem cell‐derived neurons can integrate into adult host neural networks also in a human‐to‐human grafting situation, thereby supporting their potential future clinical use to promote recovery by neuronal replacement in the patient's diseased brain.
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title_short	Grafted human pluripotent stem cell‐derived cortical neurons integrate into adult human cortical neural circuitry
url	https://doi.org/10.1002/sctm.20-0134 https://doaj.org/article/181e28f31b85430e89ba814c4933f424 https://doaj.org/toc/2157-6564 https://doaj.org/toc/2157-6580
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author2	Cecilia Laterza Sara Palma‐Tortosa Giedre Kvist Emanuela Monni Oleg Tsupykov Daniel Tornero Naomi Uoshima Jordi Soriano Johan Bengzon Gianvito Martino Galyna Skibo Olle Lindvall Zaal Kokaia
author2Str	Cecilia Laterza Sara Palma‐Tortosa Giedre Kvist Emanuela Monni Oleg Tsupykov Daniel Tornero Naomi Uoshima Jordi Soriano Johan Bengzon Gianvito Martino Galyna Skibo Olle Lindvall Zaal Kokaia
ppnlink	680320539
callnumber-subject	R - General Medicine
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doi_str	10.1002/sctm.20-0134
callnumber-a	R5-920
up_date	2024-07-03T17:22:00.409Z
_version_	1803579367527284736
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Studies in different animal models have raised the possibility that transplantation of human cortical neuronal progenitors, generated from pluripotent stem cells, might be developed into a novel therapeutic strategy for disorders affecting cerebral cortex. For example, we have shown that human long‐term neuroepithelial‐like stem (lt‐NES) cell‐derived cortical neurons, produced from induced pluripotent stem cells and transplanted into stroke‐injured adult rat cortex, improve neurological deficits and establish both afferent and efferent morphological and functional connections with host cortical neurons. So far, all studies with human pluripotent stem cell‐derived neurons have been carried out using xenotransplantation in animal models. Whether these neurons can integrate also into adult human brain circuitry is unknown. Here, we show that cortically fated lt‐NES cells, which are able to form functional synaptic networks in cell culture, differentiate to mature, layer‐specific cortical neurons when transplanted ex vivo onto organotypic cultures of adult human cortex. The grafted neurons are functional and establish both afferent and efferent synapses with adult human cortical neurons in the slices as evidenced by immuno‐electron microscopy, rabies virus retrograde monosynaptic tracing, and whole‐cell patch‐clamp recordings. 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Grafted human pluripotent stem cell‐derived cortical neurons integrate into adult human cortical neural circuitry

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