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NEUROSCIENCE · 2017 · IF 3.277

Kisspeptin-10 treatment generated specific GnRH expression in cells differentiated from rhesus monkey derived Lyon NSCs

Tanzeel Huma,Xintian Hu,Yuanye Ma,Andrew Willden,Joshua Rizak,Muhammad Shahab,Zhengbo Wang

Embryonic stem cells (ESCs) have enormous potential as novel cell-based therapies, but their effectiveness depends on stem cell differentiation and specific signaling regulators, which remain poorly understood. In this study, a kisspeptin peptide (KP-10) was used at different dosages to determine whether rhesus macaque-derived tau GFP-Lyon ES cells underwent kisspeptin-specific neuronal differentiation. It was found that KP-10 exhibited an anti-proliferative effect on the cells and led to morphological changes and cellular differentiation consistent with neuronal stem cell (NSC) development. The cells differentiated into Gonadotrophin Releasing Hormone (GnRH) neuronal-like cell types in response to the KP-10 treatment. There has been a previously observed connection between kisspeptin signaling, GnRH neurons and their dysfunction found in congenital disorders like idiopathic hypogonadotropic hypogonadism (IHH). Although therapeutics are a still a far-off goal, the formation and development of GnRH-positive neuronal-like cells following the application of KP-10 to Lyon NSC cells opens the door for future NSC-based therapies to treat specific reproductive disorders.

CAS / MDL: 30525-89-4
研究领域: 神经科学 · 生殖生物学 · 干细胞研究
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ADVANCED FUNCTIONAL MATERIALS · 2022 ·Vol. 32 ·期 31 ·2203492 · IF 19.924

HAp Thermosensitive Nanohydrogel Cavities Act as Brood Pouches to Incubate and Control-Release NSCs for Rapid Spinal Cord Injury Therapy

Min Hao,Dapeng Zhang,Wenhan Wang,Zhijian Wei,Jiazhi Duan,Jianlong He,Xiaohong Kong,Yuanhua Sang,Shiqing Feng,Hong Liu

Limitations such as the cell life span, cellular activity, and cellular diffusion outside the lesion make the direct repair of spinal cord injury (SCI) by neural stem cell (NSC) transplantation challenging. Here, an injectable hydroxyapatite (HAp) thermosensitive nanohydrogel is proposed to achieve stem cell storage and release, as well as fate regulation, for therapy. The cavities formed in situ functioned as brood pouches for cell proliferation. The enzyme-induced collapse of cavities released mouse NSCs (mNSCs) gradually and continuously. The endocytosis of HAp nanorods by encapsulated mNSCs enhanced the property of mNSC neuronal differentiation. The HAp thermosensitive nanohydrogel with mNSCs exert an inspiring therapeutic effect on a complete transected SCI model and has prospects in material design to improve SCI therapy with stem cells.

CAS / MDL: 124-30-1
研究领域: 生物医学工程 · 神经科学 · 干细胞生物学 · 材料科学
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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

Injectable hydrogel microspheres encapsulating extracellular vesicles derived from melatonin-stimulated NSCs promote neurogenesis and alleviate inflammation in spinal cord injury

Junkai Zeng,Changjiang Gu,Yu Zhuang,Kaili Lin,Youzhuan Xie,Xiongsheng Chen

Spinal cord injury (SCI) is a devastating condition that results in sensory and motor dysfunctions below the injury site. Currently, there is no effective treatment. Extracellular vesicles (NEVs) derived from neural stem cells (NSCs) have shown promising potential in exerting neuroprotective effect. However, the limited yield and quality of NEVs restrict their further application. Melatonin, an indolamine hormone that is released from the pineal gland, was used in the present study to enhance the secretion and therapeutic effects of NEVs. Compared with original NEVs, NEVs derived from melatonin-pretreated NSCs (MNEVs) exhibited improved neuroregenerative and anti-inflammatory properties in vitro . Furthermore, to achieve prolonged retention in vivo, MNEVs were encapsulated in GelMA hydrogel microspheres ( [email protected] ). After encapsulation, MNEVs effectively accumulated at the site of injury over a 28-day period. The injection of [email protected] successfully improved motor function recovery in SCI model mice. Subsequently, [email protected] inhibited the uncontrollable inflammatory response after SCI by increasing M2 macrophage polarization; in addition, MNEVs released from [email protected] exerted neuroprotective effects by promoting axonal regeneration and remyelination. Collectively, these findings reveal a promising cell-free approach for suppressing inflammation and promoting neural regeneration to treat SCI.

CAS / MDL: 760-93-0 1338-43-8
研究领域: 神经科学 · 再生医学 · 药理学 · 生物材料
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ADVANCED MATERIALS · 2023 · IF 29.4

Directed Neural Stem Cells Differentiation via Signal Communication with Ni–Zn Micromotors

Ye Feng,Chao Gao,Dazhi Xie,Lu Liu,Bin Chen,Suyi Liu,Haihong Yang,Zhan Gao,Daniela A. Wilson,Yingfeng Tu,Fei Peng

Neural stem cells (NSCs), with the capability of self-renewal, differentiation, and environment modulation, are considered promising for stroke, brain injury therapy, and neuron regeneration. Activation of endogenous NSCs, is attracting increasing research enthusiasm, which avoids immune rejection and ethical issues of exogenous cell transplantation. Yet, how to induce directed growth and differentiation in situ remain a major challenge. In this study, a pure water-driven Ni–Zn micromotor via a self-established electric–chemical field is proposed. The micromotors can be magnetically guided and precisely approach target NSCs. Through the electric–chemical field, bioelectrical signal exchange and communication with endogenous NSCs are allowed, thus allowing for regulated proliferation and directed neuron differentiation in vivo. Therefore, the Ni–Zn micromotor provides a platform for controlling cell fate via a self-established electrochemical field and targeted activation of endogenous NSCs.

研究领域: 生物医学工程 · 神经科学 · 细胞生物学 · 材料科学
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Bioactive Materials · 2022 · IF 16.874

Stratified-structural hydrogel incorporated with magnesium-ion-modified black phosphorus nanosheets for promoting neuro-vascularized bone regeneration

Yan Xu,Chao Xu,Lei He,Junjie Zhou,Tianwu Chen,Liu Ouyang,Xiaodong Guo,Yanzhen Qu,Zhiqiang Luo,Deyu Duan

Angiogenesis and neurogenesis play irreplaceable roles in bone repair. Although biomaterial implantation that mimics native skeletal tissue is extensively studied, the nerve-vascular network reconstruction is neglected in the design of biomaterials. Our goal here is to establish a periosteum-simulating bilayer hydrogel and explore the efficiency of bone repair via enhancement of angiogenesis and neurogenesis. In this contribution, we designed a bilayer hydrogel platform incorporated with magnesium-ion-modified black phosphorus (BP) nanosheets for promoting neuro-vascularized bone regeneration. Specifically, we incorporated magnesium-ion-modified black phosphorus ( [email protected] ) nanosheets into gelatin methacryloyl (GelMA) hydrogel to prepare the upper hydrogel, whereas the bottom hydrogel was designed as a double-network hydrogel system, consisting of two interpenetrating polymer networks composed of GelMA, PEGDA, and β-TCP nanocrystals. The magnesium ion modification process was developed to enhance BP nanosheet stability and provide a sustained release platform for bioactive ions. Our results demonstrated that the upper layer of hydrogel provided a bionic periosteal structure, which significantly facilitated angiogenesis via induction of endothelial cell migration and presented multiple advantages for the upregulation of nerve-related protein expression in neural stem cells (NSCs). Moreover, the bottom layer of the hydrogel significantly promoted bone marrow mesenchymal stem cells (BMSCs) activity and osteogenic differentiation. We next employed the bilayer hydrogel structure to correct rat skull defects. Based on our radiological and histological examinations, the bilayer hydrogel scaffolds markedly enhanced early vascularization and neurogenesis, which prompted eventual bone regeneration and remodeling. Our current strategy paves way for designing nerve-vascular network biomaterials for bone regeneration.

研究领域: 生物材料 · 组织工程 · 骨再生 · 干细胞生物学
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