Interneuron origins in the embryonic porcine medial ganglionic eminence

Casalia, Mariana L.; Li, Tina; Ramsay, Harrison; Ross, P. Joel; Paredes, Mercedes F.; Baraban, Scott C.

doi:10.1523/jneurosci.2738-20.2021

Cited by 9 publications

(10 citation statements)

References 74 publications

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“…To translate this strategy to larger mammals, we adapted a protocol using fetal pigs, a well-established source for xenotransplantation tissue. 15 A recent demonstration that porcine embryonic MGE progenitors migrate and differentiate into GABA-expressing interneurons in a manner similar to that described for murine embryonic MGE progenitors used for cell transplantation therapy 10 established this porcine cell source as a viable candidate for treating larger animals. Because California sea lions with DA toxicosis represent a well-characterized example of acquired epilepsy in wildlife, and because prior studies described unilateral hippocampal atrophy with loss of inhibitory hippocampal interneurons in some of these animals, 6 , 16 it is not entirely surprising that successful MGE-based treatment of a sea lion mimics prior mouse studies.…”

Section: Discussionmentioning

confidence: 89%

“…Progenitor cells harvested from porcine embryos were prepared. 10 Freeze-thawed porcine embryonic MGE progenitor cells were prepared, and >90% viability was confirmed on-site, as described. 10 Procurement and preparation of porcine MGE progenitor cells is covered by a University of California, San Francisco Institutional Animal Care and Use Committee protocol (approval no.…”

Section: Methodsmentioning

confidence: 99%

“…Building on these studies, we recently established a protocol to harvest porcine MGE progenitors as a tissue source for xenotransplantation. 10 Progenitor cell xenotransplantation into marine mammals, specifically epileptic sea lions, has never been attempted, but, if successful, it could provide a route to disease-modifying therapies.…”

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confidence: 99%

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Xenotransplantation of porcine progenitor cells in an epileptic California sea lion (Zalophus californianus): illustrative case

Simeone¹,

Andrews

Johnson³

et al. 2022

Journal of Neurosurgery: Case Lessons

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BACKGROUND Domoic acid (DA) is a naturally occurring neurotoxin harmful to marine animals and humans. California sea lions exposed to DA in prey during algal blooms along the Pacific coast exhibit significant neurological symptoms, including epilepsy with hippocampal atrophy. OBSERVATIONS Here the authors describe a xenotransplantation procedure to deliver interneuron progenitor cells into the damaged hippocampus of an epileptic sea lion with suspected DA toxicosis. The sea lion has had no evidence of seizures after the procedure, and clinical measures of well-being, including weight and feeding habits, have stabilized. LESSONS These preliminary results suggest xenotransplantation has improved the quality of life for this animal and holds tremendous therapeutic promise.

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Section: Discussionmentioning

confidence: 89%

Section: Methodsmentioning

confidence: 99%

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Xenotransplantation of porcine progenitor cells in an epileptic California sea lion (Zalophus californianus): illustrative case

Simeone¹,

Andrews

Johnson³

et al. 2022

Journal of Neurosurgery: Case Lessons

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“…Usually, fresh embryonic cells or primary cultured cells are preferred for these studies. It has been criticized that human stem cell–derived MGE-like cells exhibit little migration and do not differentiate into subtypes seen in embryonic MGE progenitors 47 . In our experience, limited migration and delayed development were observed.…”

Section: Discussionmentioning

confidence: 99%

MGE-Like Neural Progenitor Cell Survival and Expression of Parvalbumin and Proenkephalin in a Jaundiced Rat Model of Kernicterus

et al. 2022

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Kernicterus is a permanent condition caused by brain damage from bilirubin toxicity. Dystonia is one of the most debilitating symptoms of kernicterus and results from damage to the globus pallidus (GP). One potential therapeutic strategy to treat dystonia in kernicterus is to replace lost GP neurons and restore basal ganglia circuits through stem cell transplantation. Toward this end, we differentiated human embryonic stem cells (hESCs) into medial ganglion eminence (MGE; the embryological origin of most of the GP neurons)-like neural precursor cells (NPCs). We determined neurochemical phenotype in cell culture and after transplanting into the GP of jaundiced Gunn rats. We also determined grafted cell survival as well as migration, distribution, and morphology after transplantation. As in the GP, most cultured MGE-like NPCs expressed γ-aminobutyric acid (GABA), with some co-expressing markers for parvalbumin (PV) and others expressing markers for pro-enkephalin (PENK). MGE-like NPCs survived in brains at least 7 weeks after transplantation, with most aggregating near the injection site. Grafted cells expressed GABA and PV or PENK as in the normal GP. Although survival was low and the maturity of grafted cells varied, many cells produced neurite outgrowth. While promising, our results suggest the need to further optimize the differentiation protocol for MGE-like NPC for potential use in treating dystonia in kernicterus.

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“…The balance between excitation and inhibition in the cortical neural circuits is maintained by GABAergic interneurons ( Wang et al, 2016 ). In animals and humans, interneuron loss or malfunctioning can result in mood disorders, working memory disorders, or cognitive decline ( Casalia et al, 2021 ; Williams and Riedemann, 2021 ), leading to epilepsy ( Knopp et al, 2008 ), Alzheimer’s Disease (AD) ( Fu et al, 2017 ; Najm et al, 2020 ), schizophrenia ( Dienel and Lewis, 2019 ; Van Derveer et al, 2021 ), autism spectrum disorder (ASD) ( Shin et al, 2021 ; Deemyad et al, 2022 ) and other neurological disorders. Researches have revealed that MGE-derived interneuron transplantation offers hope for treating these diseases ( De la Cruz et al, 2011 ; Perez and Lodge, 2013 ; Upadhya et al, 2019 ; Lu et al, 2020 ; Southwell et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Application of Medial Ganglionic Eminence Cell Transplantation in Diseases Associated With Interneuron Disorders

Han

2022

Front. Cell. Neurosci.

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Excitatory projection neurons and inhibitory interneurons primarily accomplish the neural activity of the cerebral cortex, and an imbalance of excitatory-inhibitory neural networks may lead to neuropsychiatric diseases. Gamma-aminobutyric acid (GABA)ergic interneurons mediate inhibition, and the embryonic medial ganglionic eminence (MGE) is a source of GABAergic interneurons. After transplantation, MGE cells migrate to different brain regions, differentiate into multiple subtypes of GABAergic interneurons, integrate into host neural circuits, enhance synaptic inhibition, and have tremendous application value in diseases associated with interneuron disorders. In the current review, we describe the fate of MGE cells derived into specific interneurons and the related diseases caused by interneuron loss or dysfunction and explore the potential of MGE cell transplantation as a cell-based therapy for a variety of interneuron disorder-related diseases, such as epilepsy, schizophrenia, autism spectrum disorder, and Alzheimer’s disease.

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Interneuron origins in the embryonic porcine medial ganglionic eminence

Cited by 9 publications

References 74 publications

Xenotransplantation of porcine progenitor cells in an epileptic California sea lion (Zalophus californianus): illustrative case

Xenotransplantation of porcine progenitor cells in an epileptic California sea lion (Zalophus californianus): illustrative case

MGE-Like Neural Progenitor Cell Survival and Expression of Parvalbumin and Proenkephalin in a Jaundiced Rat Model of Kernicterus

Application of Medial Ganglionic Eminence Cell Transplantation in Diseases Associated With Interneuron Disorders

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