Brain injury environment critically influences the connectivity of transplanted neurons DOI Creative Commons
Sofia Grade, Judith M. Thomas, Yvette Zarb

et al.

Science Advances, Journal Year: 2022, Volume and Issue: 8(23)

Published: June 10, 2022

Cell transplantation is a promising approach for the reconstruction of neuronal circuits after brain damage. Transplanted neurons integrate with remarkable specificity into circuitries mouse cerebral cortex affected by ablation. However, it remains unclear how perform in local environment undergoing reactive gliosis, inflammation, macrophage infiltration, and scar formation, as traumatic injury (TBI). To elucidate this, we transplanted cells from embryonic TBI-injured, inflamed-only, or intact adult mice. Brain-wide quantitative monosynaptic rabies virus (RABV) tracing unraveled graft inputs correct regions across all conditions, pronounced differences: scarce inflamed versus exuberant TBI. In latter, initial overshoot followed pruning, only few input persisting at 3 months. Proteomic profiling identifies candidate molecules regulation synaptic yield, pivotal parameter to tailor functional restoration circuits.

Language: Английский

New approaches for brain repair—from rescue to reprogramming DOI
Roger A. Barker, Magdalena Götz, Malin Parmar

et al.

Nature, Journal Year: 2018, Volume and Issue: 557(7705), P. 329 - 334

Published: May 8, 2018

Language: Английский

Citations

193
Vascularization and Engraftment of Transplanted Human Cerebral Organoids in Mouse Cortex DOI Creative Commons
Nicolas Daviaud, Roland H. Friedel, Hongyan Zou

et al.

eNeuro, Journal Year: 2018, Volume and Issue: 5(6), P. ENEURO.0219 - 18.2018

Published: Nov. 1, 2018

Neural stem cells (NSCs) hold great promise for neural repair in cases of CNS injury and neurodegeneration; however, conventional cell-based transplant methods face the challenges poor survival inadequate neuronal differentiation. Here, we report an alternative, tissue-based transplantation strategy whereby cerebral organoids derived from human pluripotent (PSCs) were grafted into lesioned mouse cortex. Cerebral organoid transplants exhibited enhanced robust vascularization host brain as compared to dissociated progenitor (NPCs). Engrafted harbored a large NSC pool displayed multilineage neurodifferentiation at two four weeks after grafting. therefore represent promising alternative source NSCs or fetal tissues transplantation, they contain set neuroprogenitors differentiated neurons structured organization. may also offer unique experimental paradigm modeling neurodevelopment diseases context vascularized cortical tissue.

Language: Английский

Citations

187
Inducing Different Neuronal Subtypes from Astrocytes in the Injured Mouse Cerebral Cortex DOI Creative Commons
Nicola Mattugini, Riccardo Bocchi, Volker Scheuß

et al.

Neuron, Journal Year: 2019, Volume and Issue: 103(6), P. 1086 - 1095.e5

Published: Sept. 1, 2019

Astrocytes are particularly promising candidates for reprogramming into neurons, as they maintain some of the original patterning information from their radial glial ancestors. However, to which extent position astrocytes influences fate reprogrammed neurons remains unknown. To elucidate this, we performed stab wound injury covering an entire neocortical column, including gray matter (GM) and white (WM), targeted local reactive via injecting FLEx switch (Cre-On) adeno-associated viral (AAV) vectors mGFAP-Cre mice. Single proneural factors were not sufficient adequate reprogramming, although combination with nuclear receptor-related 1 protein (Nurr1) improved efficiency. Nurr1 Neurogenin 2 (Ngn2) resulted in high-efficiency that develop lamina-specific hallmarks, appropriate long-distance axonal projections. Surprisingly, WM, did observe any thereby unveiling a crucial role region- layer-specific differences astrocyte reprogramming.

Language: Английский

Citations

140
Neural tissue engineering with structured hydrogels in CNS models and therapies DOI Creative Commons
Julian H. George, Chia‐Chen Hsu, Nguyen Thuy Ba Linh

et al.

Biotechnology Advances, Journal Year: 2019, Volume and Issue: 42, P. 107370 - 107370

Published: March 19, 2019

The development of techniques to create and use multiphase microstructured hydrogels (granular or microgels) has enabled the generation cultures with more biologically relevant architecture structured is especially pertinent new types central nervous system (CNS) culture models therapies. We review material choice customisation hydrogel structure, as well in developmental models. Combining developmentally tissue approaches will enable treatments repair damaged CNS architecture.

Language: Английский

Citations

127
Direct neuronal reprogramming: Fast forward from new concepts toward therapeutic approaches DOI Creative Commons
Riccardo Bocchi, Giacomo Masserdotti, Magdalena Götz

et al.

Neuron, Journal Year: 2021, Volume and Issue: 110(3), P. 366 - 393

Published: Dec. 18, 2021

Language: Английский

Citations

86
The role of neurogenesis in neurorepair after ischemic stroke DOI
Bruno Lemes Marques, Gustavo Almeida Carvalho,

Elis M.M. Freitas

et al.

Seminars in Cell and Developmental Biology, Journal Year: 2019, Volume and Issue: 95, P. 98 - 110

Published: Jan. 18, 2019

Language: Английский

Citations

80
Axonal Extensions along Corticospinal Tracts from Transplanted Human Cerebral Organoids DOI Creative Commons
T Kitahara, Hideya Sakaguchi, Asuka Morizane

et al.

Stem Cell Reports, Journal Year: 2020, Volume and Issue: 15(2), P. 467 - 481

Published: July 16, 2020

The reconstruction of lost neural circuits by cell replacement is a possible treatment for neurological deficits after cerebral cortex injury. Cerebral organoids can be novel source transplantation, but because the cellular composition changes along time course development, it remains unclear which developmental stage most suitable reconstructing corticospinal tract. Here, we transplanted human embryonic stem cell-derived at 6 or 10 weeks differentiation (6w- 10w-organoids) into mouse cortices. 6w-organoids extended more axons tract caused graft overgrowth with higher percentage proliferative cells. Axonal extensions from 10w-organoids were smaller in number enhanced when grafted 1 week brain Finally, cynomolgus monkey brains. These results contribute to development cell-replacement therapy injury and stroke.

Language: Английский

Citations

73
Functional neurological restoration of amputated peripheral nerve using biohybrid regenerative bioelectronics DOI Creative Commons
Amy E. Rochford, Alejandro Carnicer‐Lombarte, Malak Kawan

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(12)

Published: March 22, 2023

The development of neural interfaces with superior biocompatibility and improved tissue integration is vital for treating restoring neurological functions in the nervous system. A critical factor to increase resolution mapping neuronal inputs onto implants. For this purpose, we have developed a new category interface comprising induced pluripotent stem cell (iPSC)-derived myocytes as biological targets peripheral nerve that are grafted flexible electrode arrays. We show long-term survival functional biohybrid device carrying human iPSC-derived cells forearm bundle freely moving rats, following 4 weeks implantation. By improving tissue-electronics an intermediate layer, demonstrated enhanced electrical recording vivo first step toward restorative therapies using regenerative bioelectronics.

Language: Английский

Citations

37
Hydrogel oxygen reservoirs increase functional integration of neural stem cell grafts by meeting metabolic demands DOI Creative Commons
Yi Wang,

Elizabeth R. Zoneff,

Josiah Thomas

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Jan. 28, 2023

Injectable biomimetic hydrogels have great potential for use in regenerative medicine as cellular delivery vectors. However, they can suffer from issues relating to hypoxia, including poor cell survival, differentiation, and functional integration owing the lack of an established vascular network. Here we engineer a hybrid myoglobin:peptide hydrogel that concomitantly deliver stem cells oxygen brain support engraftment until vascularisation occur naturally. We show this modulate fate specification within progenitor grafts, resulting significant increase neuronal differentiation. find addition myoglobin results more extensive innervation host tissue grafted cells, which is essential replacement strategies ensure synaptic connectivity. This approach could result greater cell-derived grafts treatment neural injuries diseases affecting central peripheral nervous systems.

Language: Английский

Citations

32
Recent advances in tissue repair of the blood-brain barrier after stroke DOI Creative Commons

Liujie Qi,

Fei Wang,

Xiaojing Sun

et al.

Journal of Tissue Engineering, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 1, 2024

The selective permeability of the blood-brain barrier (BBB) enables necessary exchange substances between brain parenchyma and circulating blood is important for normal functioning central nervous system. Ischemic stroke inflicts damage upon BBB, triggering adverse outcomes such as cerebral edema, hemorrhagic transformation, aggravated neuroinflammation. Therefore, effective repair damaged BBB after neovascularization that allows unique transfer from recovery function. This review focuses on four therapies have effects tissue in last seven years. Most these new show increased expression tight-junction proteins, some beneficial results terms enhanced pericyte coverage at injured vessels. also briefly outlines three classes approaches their mechanisms promoting neoangiogenesis following a stroke.

Language: Английский

Citations

12