Structural and functional integration of human forebrain organoids with the injured adult rat visual system

Jgamadze, Dennis; Lim, James; Zhang, Zhijian; Harary, Paul M.; Germi, James; Mensah-Brown, Kobina; Adam, Christopher D.; Mirzakhalili, Ehsan; Singh, Shikha; Gu, Jiahe Ben; Blue, Rachel; Dedhia, Mehek; Fu, Marissa; Jacob, Fadi; Qian, Xuyu; Gagnon, Kimberly G.; Sergison, Matthew; Fruchet, Oceane; Rahaman, Imon; Wang, Huadong; Xu, Fuqiang; Xiao, R.; Contreras, Diego; Wolf, John A.; Song, Hongjun; Ming, Guo‐li; Chen, H. Isaac

doi:10.1016/j.stem.2023.01.004

Cited by 66 publications

(30 citation statements)

References 65 publications

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“…Previous studies in rats have shown that integration of transplanted NSCs into the host neural circuitry is important for improving the e cacy of NSC transplantation [30][31] . Recent studies have also shown that transplanted human brain organoids can structurally and functionally integrate into the visual system after cortical injury, demonstrating the importance of functional integration in the treatment of TBI by cell transplantation 32 . In this study, the transplanted NSCs not only showed cellular activity but also expressed PSD-95 and Synapsin I, indicating that there were synaptic connections between transplanted NSCs and host neurons; this suggests that transplanted NSCs could repair damage tissue in the lesion site in situ and reduce secondary apoptosis in nearby brain areas.…”

Section: Discussionmentioning

confidence: 97%

“…In recent years, extensive research on the effectiveness of NSCs in the treatment of TBI has been conducted. Cortical TBI usually results in a larger lesion cavity, and transplanted cells can easily enter the CSF 32 . Therefore, a previously developed mechanical injury method 19 was used to damage the visual and sensory cortices, and then NSCs were transplanted into the injury site.…”

Section: Discussionmentioning

confidence: 99%

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Neural stem cell transplantation rescues cortical damage in rhesus monkey models of traumatic brain injury

Liu

Dong

Huang

et al. 2023

Preprint

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Background Cortical traumatic brain injury (TBI) is a major cause of cognitive impairment accompanied by motor and behavioural deficits. Cell transplantation is the most promising treatment, and how to keep the transplanted cells are not removed via cerebrospinal fluid (CSF) is the key problem. Methods In this study, we transplanted neural stem cells (NSCs) and simultaneously injected bFGF/EGF into the cortex (visual and sensory cortices) of rhesus monkeys with superficial TBI. Results The results showed that the transplanted NSCs did not enter the CSF and were confined to the transplantation site for at least one year. The transplanted NSCs differentiated into mature neurons that formed synaptic connections with host neurons, but glial scar formation between the graft and the host tissue did not occur. Conclusions This study is the first to explore the efficacy of transplanting NSCs into the superficial cerebral cortex of rhesus monkeys after TBI, and the results show the ability of NSCs to survive long term and differentiate into neurons, demonstrating the clinical translation potential of NSC transplantation for cortical TBI.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Neural stem cell transplantation rescues cortical damage in rhesus monkey models of traumatic brain injury

Liu

Dong

Huang

et al. 2023

Preprint

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“…This transplantation procedure effectively restored impaired tissue and reinstated motor functions 134,135 . Furthermore, upon transplantation into the visual cortex of rat brains, the brain organoids exhibited seamless integration into the host tissue, exhibiting progressive development of blood vessels, enlargement in size, generation of neuronal projections, and establishment of synaptic connections 136,137 . Moreover, the introduction of human brain organoids into the brains of neonatal rats, specifically those aged 2–3 days, a critical period characterized by ongoing neural connectivity development, resulted in the subsequent growth and occupation of approximately one‐third of the rat brain hemisphere by these transplanted human brain organoids 132 .…”

Section: Future Strategies For Treating Neurological Diseasesmentioning

confidence: 98%

Role and limitation of cell therapy in treating neurological diseases

Li,

Tao

et al. 2024

Ibrain

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The central role of the brain in governing systemic functions within human physiology underscores its paramount significance as the focal point of physiological regulation. The brain, a highly sophisticated organ, orchestrates a diverse array of physiological processes encompassing motor control, sensory perception, cognition, emotion, and the regulation of vital functions, such as heartbeat, respiration, and hormonal equilibrium. A notable attribute of neurological diseases manifests as the depletion of neurons and the occurrence of tissue necrosis subsequent to injury. The transplantation of neural stem cells (NSCs) into the brain exhibits the potential for the replacement of lost neurons and the reconstruction of neural circuits. Furthermore, the transplantation of other types of cells in alternative locations can secrete nutritional factors that indirectly contribute to the restoration of nervous system equilibrium and the mitigation of neural inflammation. This review summarized a comprehensive investigation into the role of NSCs, hematopoietic stem cells, mesenchymal stem cells, and support cells like astrocytes and microglia in alleviating neurological deficits after cell infusion. Moreover, a thorough assessment was undertaken to discuss extant constraints in cellular transplantation therapies, concurrently delineating indispensable model‐based methodologies, specifically on organoids, which were essential for guiding prospective research initiatives in this specialized field.

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“…The restorative capacity of hPSC-based organoid transplantation has been demonstrated in the intestine (20)(21)(22), pancreas (23,24), liver (24), retina (25), brain (26,27), and lung (28). Human cardiac organoids have proven to be an excellent platform for modeling human cardiac disease and drug cardiotoxicity (29); however, their therapeutic potential to treat infarcted hearts requires further investigation.…”

Section: Introductionmentioning

confidence: 99%

Nanowired human cardiac organoid transplantation enables highly efficient and effective recovery of infarcted hearts

et al. 2023

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Human cardiac organoids hold remarkable potential for cardiovascular disease modeling and human pluripotent stem cell–derived cardiomyocyte (hPSC-CM) transplantation. Here, we show cardiac organoids engineered with electrically conductive silicon nanowires (e-SiNWs) significantly enhance the therapeutic efficacy of hPSC-CMs to treat infarcted hearts. We first demonstrated the biocompatibility of e-SiNWs and their capacity to improve cardiac microtissue engraftment in healthy rat myocardium. Nanowired human cardiac organoids were then engineered with hPSC-CMs, nonmyocyte supporting cells, and e-SiNWs. Nonmyocyte supporting cells promoted greater ischemia tolerance of cardiac organoids, and e-SiNWs significantly improved electrical pacing capacity. After transplantation into ischemia/reperfusion–injured rat hearts, nanowired cardiac organoids significantly improved contractile development of engrafted hPSC-CMs, induced potent cardiac functional recovery, and reduced maladaptive left ventricular remodeling. Compared to contemporary studies with an identical injury model, greater functional recovery was achieved with a 20-fold lower dose of hPSC-CMs, revealing therapeutic synergy between conductive nanomaterials and human cardiac organoids for efficient heart repair.

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Structural and functional integration of human forebrain organoids with the injured adult rat visual system

Cited by 66 publications

References 65 publications

Neural stem cell transplantation rescues cortical damage in rhesus monkey models of traumatic brain injury

Neural stem cell transplantation rescues cortical damage in rhesus monkey models of traumatic brain injury

Role and limitation of cell therapy in treating neurological diseases

Nanowired human cardiac organoid transplantation enables highly efficient and effective recovery of infarcted hearts

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