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1.
Int J Mol Sci ; 25(15)2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39126108

ABSTRACT

Damage to the central nervous system (CNS) often leads to irreversible neurological deficits, and there are currently few effective treatments available. However, recent advancements in regenerative medicine have identified CNS organoids as promising therapeutic options for addressing CNS injuries. These organoids, composed of various neurons and supporting cells, have shown potential for direct repair at injury sites. CNS organoids resemble the structure and function of actual brain tissue, which allows them to adapt and function well within the physiological environment when transplanted into injury sites. Research findings suggest that CNS organoids can replace damaged neurons, form new neural connections, and promote neural recovery. This review highlights the emerging benefits, evaluates preclinical transplantation outcomes, and explores future strategies for optimizing neuroregeneration using CNS organoids. With continued research and technological advancements, these organoids could provide new hope for patients suffering from neurological deficits.


Subject(s)
Central Nervous System , Organoids , Humans , Organoids/cytology , Organoids/transplantation , Nerve Regeneration , Animals , Neurons/cytology , Neurons/physiology , Regenerative Medicine/methods
2.
Int J Mol Sci ; 25(14)2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39062993

ABSTRACT

Since the emergence of the first cerebral organoid (CO) in 2013, advancements have transformed central nervous system (CNS) research. Initial efforts focused on studying the morphogenesis of COs and creating reproducible models. Numerous methodologies have been proposed, enabling the design of the brain organoid to represent specific regions and spinal cord structures. CNS organoids now facilitate the study of a wide range of CNS diseases, from infections to tumors, which were previously difficult to investigate. We summarize the major advancements in CNS organoids, concerning morphogenetic designs and disease models. We examine the development of fabrication procedures and how these advancements have enabled the generation of region-specific brain organoids and spinal cord models. We highlight the application of these organoids in studying various CNS diseases, demonstrating the versatility and potential of organoid models in advancing our understanding of complex conditions. We discuss the current challenges in the field, including issues related to reproducibility, scalability, and the accurate recapitulation of the in vivo environment. We provide an outlook on prospective studies and future directions. This review aims to provide a comprehensive overview of the state-of-the-art CNS organoid research, highlighting key developments, current challenges, and prospects in the field.


Subject(s)
Central Nervous System , Organoids , Humans , Animals , Central Nervous System Diseases/pathology , Morphogenesis , Models, Biological
3.
Int J Mol Sci ; 25(15)2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39125746

ABSTRACT

Osteoporotic vertebral compression fractures (OVCFs) are the most prevalent fractures among patients with osteoporosis, leading to severe pain, deformities, and even death. This study explored the use of ectopic embryonic calvaria derived mesenchymal stem cells (EE-cMSCs), which are known for their superior differentiation and proliferation capabilities, as a potential treatment for bone regeneration in OVCFs. We evaluated the impact of EE-cMSCs on osteoclastogenesis in a RAW264.7 cell environment, which was induced by the receptor activator of nuclear factor kappa-beta ligand (RANKL), using cytochemical staining and quantitative real-time PCR. The osteogenic potential of EE-cMSCs was evaluated under various hydrogel conditions. An osteoporotic vertebral body bone defect model was established by inducing osteoporosis in rats through bilateral ovariectomy and creating defects in their coccygeal vertebral bodies. The effects of EE-cMSCs were examined using micro-computed tomography (µCT) and histology, including immunohistochemical analyses. In vitro, EE-cMSCs inhibited osteoclast differentiation and promoted osteogenesis in a 3D cell culture environment using fibrin hydrogel. Moreover, µCT and histological staining demonstrated increased new bone formation in the group treated with EE-cMSCs and fibrin. Immunostaining showed reduced osteoclast activity and bone resorption, alongside increased angiogenesis. Thus, EE-cMSCs can effectively promote bone regeneration and may represent a promising therapeutic approach for treating OVCFs.


Subject(s)
Cell Differentiation , Disease Models, Animal , Mesenchymal Stem Cells , Osteogenesis , Osteoporosis , Skull , Animals , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Rats , Skull/pathology , Mice , Osteoporosis/pathology , Osteoporosis/metabolism , Osteoporosis/therapy , Female , RAW 264.7 Cells , Osteoclasts/metabolism , Bone Regeneration , Rats, Sprague-Dawley , Mesenchymal Stem Cell Transplantation/methods , Vertebral Body/metabolism , X-Ray Microtomography , Osteoporotic Fractures/therapy , Osteoporotic Fractures/metabolism , Osteoporotic Fractures/pathology
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