STEM CELLS AND DEVELOPMENT
·
2023
·
IF 4
Mr. Genghua Xu,Ms. Nuoya Liu,Ms. Yaqing Qiu,Ms. Jiayu Qi,Prof. Danyan Zhu
The histamine H3 receptor, prominently expressed in neurons with a minor presence in glial cells, acts as both an autoreceptor and an alloreceptor, controlling the release of histamine and other neurotransmitters. The receptor impacts various essential physiological processes. Our team's initial investigations had demonstrated that the histamine H3 receptor antagonists could facilitate the nerve regeneration via promoting the histamine H1 receptors on primary neural stem cells in the traumatic brain injury mouse, which suggested the potential of histamine H3 receptor as a promising target for treating neurological disorders and promoting nerve regeneration. Pitolisant (PITO) is the only histamine H3 receptor antagonist approved by the FDA for treating narcolepsy. However, there are no reports on Pitolisant in neural development or regeneration, and it is urgent to be further studied in strong biological activity models in vitro. The embryonic stem (ES) cells were differentiated into neural cells in vitro, which replicated the neurodevelopmental processes that occur in vivo. It also provided an alternative model for studying neurodevelopmental processes and testing drugs for neurological conditions. Therefore, we aimed to elucidate the regulatory role of Pitolisant in the early differentiation of ES cells into neural cells. Our results demonstrated that Pitolisant could promote the differentiation of ES cells towards neural stem cells (NSCs) and stimulated the formation of growth cones. Furthermore, Pitolisant was capable of inducing the polarization of NSCs through the cAMP-LKB1-SAD/MARK2 pathway, but had no significant effect on later neuronal maturation. Pitolisant altered mitochondrial morphology and up-regulated the levels of mitochondrial-related proteins TOM20, Drp1, and p-Drp1, and reversed the inhibitory effect of Mdivi-1 on mitochondrial fission during the early neural differentiation of ES cells. Additionally, Pitolisant induced the increase in cytosolic Ca2+. Our study provided an experimental foundation for the potential application of histamine H3 receptor-targeted modulators in the field of neuroregeneration.
研究领域:
神经科学
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干细胞生物学
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药理学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Li-Ming Li,Min Han,Xin-Chi Jiang,Xian-Zhen Yin,Fu Chen,Tian-Yuan Zhang,Hao Ren,Ji-Wen Zhang,Ting-Jun Hou,Zhong Chen,Hong-Wei Ou-Yang,Yasuhiko Tabata,You-Qing Shen,Jian-Qing Gao
Spinal cord injury (SCI) is one of the most devastating injuries. Treatment strategies for SCI are required to overcome comprehensive issues. Implantation of biomaterial scaffolds and stem cells has been demonstrated to be a promising strategy. However, a comprehensive recovery effect is difficult to achieve. In the comprehensive treatment process, the specific roles of the implanted scaffolds and of stem cells in combined strategy are usually neglected. In this study, a peptide-modified scaffold is developed based on hyaluronic acid and an adhesive peptide PPFLMLLKGSTR. Synchrotron radiation micro computed tomography measurement provides insights to the three-dimensional inner topographical property and perspective porous structure of the scaffold. The modified scaffold significantly improves cellular survival and adhesive growth of mesenchymal stem cells during 3D culture in vitro. After implantation in transected spinal cord, the modified scaffold and mesenchymal stems are found to function in synergy to restore injured spinal cord tissue, with respective strengths. Hindlimb motor function scores exhibit the most significant impact of the composite implant at 2 weeks post injury, which is the time secondary injury factors begin to take hold. Investigation on the secondary injury factors including inflammatory response and astrocyte overactivity at 10 days post injury reveals the possible underlying reason. Implants of the scaffold, cells, and especially the combination of both elicit inhibitory effects on these adverse factors. The study develops a promising implant for spinal cord tissue engineering and reveals the roles of the scaffold and stem cells. More importantly, the results provide the first understanding of the bioactive peptide PPFLMLLKGSTR concerning its functions on mesenchymal stem cells and spinal cord tissue restoration.
研究领域:
生物医学工程
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干细胞生物学
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神经科学
·
组织工程
✓ 已验证
DOI
PubMed
高影响因子
COMPOSITES PART B-ENGINEERING
·
2022
·
IF 11.322
Kunxi Zhang,Wei Zhao,Haowei Fang,Xi Chen,Yuhao Hong,Jingbo Yin,Chen Wang
Stem cell spheroids possess higher viability and up-regulated paracrine function, showing advanced curative effect. However, the barrier of efficient spheroids preparation and application limits spheroids application in clinical. The present study developed an “all-in-one” porous granular hydrogel to not only produce numerous stem cell spheroids, but also apply the spheroids conveniently for wound treatment. Poly (sulfobetaine methacrylate) (PSBMA)-based microgels that cross-linked with disulfide bonds assembled, and further cross-linked by in-situ co-polymerized poly (N-isopropylacrylamide-co-sulfobetaine methacrylate) (P(NIPAM- co -SBMA)) to prepare porous composite granular hydrogel with bulk, shear-thinning, self-healing, hundred micron pores and low-fouling feature. Adipose-derived stem cells (ASCs) seeded into the porous composite granular hydrogel formed numerous spheroids inside the hundred micron pores. The porous composite granular hydrogel carrying produced ASC spheroids were spread onto the wound like creams. Then, PSBMA-based microgels dissolved quickly and spontaneously, forming extensive pores with the size less than 10 μm, which ensured the effective release of growth factors produced by stem cell spheroids into the wound. In vivo evaluation confirmed that ASC spheroids up-regulated the secretion of anti-inflammatory factors and reparative growth factors, effectively inhibited the local inflammatory response of wounds in the early stage of wound, thus accelerating wound healing.
研究领域:
生物医学工程
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组织工程
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伤口愈合
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干细胞研究
✓ 已验证
DOI
高影响因子
CYTOTHERAPY
·
2017
·
IF 3.203
Ying Luo,Cheng Lou,Sui Zhang,Zhengyan Zhu,Qianzhe Xing,Peng Wang,Tong Liu,Hui Liu,Chenglong Li,Wenxia Shi,Zhi Du,Yingtang Gao
Background aims Human induced pluripotent stem cells (hiPSCs) are becoming increasingly popular in research endeavors due to their potential for clinical application; however, such application is challenging due to limitations such as inferior function and low induction efficiency. In this study, we aimed to establish a three-dimensional (3D) culture condition to mimic the environment in which hepatogenesis occurs in vivo to enhance the differentiation of hiPSCs for large-scale culture and high throughput BAL application. Methods We used hydrogel to create hepatocyte-like cell (HLC) spheroids in a 3D culture condition and analyzed the cell-behavior and differentiation properties of hiPSCs in a synthetic nanofiber scaffold. Results We found that treating cells with Y-27632 promoted the formation of spheroids, and the cells aggregated more rapidly in a 3D culture condition. The ALB secretion, urea production and glycogen synthesis by HLCs in 3D were significantly higher than those grown in a 2-dimensional culture condition. In addition, the metabolic activities of the CYP450 enzymes were also higher in cells differentiated in the 3D culture condition. Conclusions 3D hydrogel culture condition can promote differentiation of hiPSCs into hepatocytes. The 3D culture approach could be applied to the differentiation of hiPSCs into hepatocytes for bioartificial liver.
研究领域:
再生医学
·
干细胞研究
·
肝脏生物学
✓ 已验证
DOI
PubMed
高影响因子
HISTOCHEMISTRY AND CELL BIOLOGY
·
2021
·Vol. 156
·期 1
·47-58
·
IF 4.304
Sun Yuchuan,Li Hong,Chen Qiufang,Luo Qing,Song Guanbin
The survival of cancer stem cells is usually limited to a specific tumor microenvironment, and this microenvironment plays a vital role in the development of tumors. The mechanical properties of the microenvironment differ in different regions of solid tumors. However, in solid tumors, whether the distribution of cancer stem cells relates to the mechanical microenvironment of different regions is still unclear. In this study, we undertook a biophysical and biochemical assessment of the changes in the mechanical properties of liver tissue during the progression of liver cancer and explored the distribution of liver cancer stem cells in liver cancer tissues. Our analysis confirmed previous observations that the stiffness of liver tissue gradually increased with the progress of fibrosis. In liver cancer tissues, we found obvious mechanical heterogeneity: the core of the tumor was soft, the invasive front tissue was the hardest, and the para-cancer tissue was in an intermediate state. Interestingly, the greatest number of liver cancer stem cells was found in the invasive front part of the tumor. We finally established that stroma stiffness correlated with the number of liver cancer stem cells. These findings indicate that the distribution of liver cancer stem cells correlates with the mechanical heterogeneity of liver cancer tissue. This result provides a theoretical basis for the development of targeted therapies against the mechanical microenvironment of liver cancer stem cells.
研究领域:
肿瘤学
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生物物理学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 10
·期 4
·518-536
·
IF 6.331
Zihan Yang,Xichao Wang,Guohai Liang,Anli Yang,Jinming Li
Mesenchymal stem cells (MSCs) have multiple differentiation potentials and their clinical application is limited by controlled cell differentiation and long-term tracing in vivo. Here, we developed an upconversion nanoparticle (UCNP)-based nanoplatform for the photocontrolled chondrogenic differentiation and long-term tracking of MSCs in vivo. The UCNP nanoplatform could convert 980 nm near-infrared (NIR) light into UV/blue light (365/475 nm) and green/red light (545/647 nm) through Tm/Er doping. Then, the upconverted UV/blue light was used to drive the photosensitive molecule azobenzene (azo) that was modified in mesoporous silica to constantly change its conformation to trigger the release of kartogenin (KGN) from the UCNPs to induce the chondrogeni differentiation of MSCs, achieving photocontrolled cell differentiation. Both in vitro and in vivo experiments demonstrated the effective induction of chondrogenic differentiation in MSCs by NIR light with the UCNP nanoplatform incubation. In addition, after inducing differentiation, the UCNP nanoplatform that remained in the cytoplasm was used as a nanoprobe to monitor the MSCs in vitro and in vivo using the upconverted green/red light under the NIR light. Therefore, the UCNP nanoplatform displayed potential to be a powerful tool for the control of cell differentiation and the simultaneous long-term tracking of MSCs in vivo for regenerative medicine.
研究领域:
纳米技术
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干细胞生物学
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再生医学
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生物医学工程
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组织工程
✓ 已验证
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2021
·
IF 9.028
Tingting Ku,Fang Hao,Xiaoxi Yang,Ziyu Rao,Qian S. Liu,Nan Sang,Francesco Faiola,Qunfang Zhou,Guibin Jiang
The tremendous potential for graphene quantum dots (GQDs) in biomedical applications has led to growing concerns of their health risks in human beings. However, present studies mainly focused on oxidative stress, apoptosis, and other general toxicity effects; the knowledge on the developmental toxicity and the related regulatory mechanisms is still far from sufficient. Our study revealed the development retardation of mouse embryonic stem cells (mESCs) caused by GQDs with a novel DNA methylation epigenetic mechanism. Specifically, GQDs were internalized into cells mainly via energy-dependent endocytosis, and a significant fraction of internalized GQDs remained in the cells even after a 48-h clearance period. Albeit with unobservable cytotoxicity or any influences on cell pluripotency, significant retardation was found in the in vitro differentiation of the mESCs into embryoid bodies (EBs) with the upregulation of Sox2 levels in GQD pretreatment groups. Importantly, this effect could be contributed by GQD-induced inhibition in CpG methylation of Sox2 through altering methyltransferase and demethyltransferase transcriptional expressions, and the demethyltransferase inhibitor, bobcat339 hydrochloride, reduced GQD-induced upregulation of Sox2. The current study first demonstrated that GQDs compromised the differentiation program of the mESCs, potentially causing development retardation. Exposure to this nanomaterial during gestation or early developmental period would cause adverse health risks and is worthy of more attention.
研究领域:
纳米技术
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干细胞生物学
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表观遗传学
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毒理学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2020
·
IF 3.644
Hao Dake,Swindell Hila Shimshi,Ramasubramanian Lalithasri,Liu Ruiwu,Lam Kit S.,Farmer Diana L.,Wang Aijun
The network structure and biological components of natural extracellular matrix (ECM) are indispensable for promoting tissue regeneration. Electrospun nanofibrous scaffolds have been widely used in regenerative medicine to provide structural support for cell growth and tissue regeneration due to their natural ECM mimicking architecture, however, they lack biological functions. Extracellular vesicles (EVs) are potent vehicles of intercellular communication due to their ability to transfer RNAs, proteins, and lipids, thereby mediating significant biological functions in different biological systems. Matrix-bound nanovesicles (MBVs) are identified as an integral and functional component of ECM bioscaffolds mediating significant regenerative functions. Therefore, to engineer EVs modified electrospun scaffolds, mimicking the structure of the natural EV-ECM complex and the physiological interactions between the ECM and EVs, will be attractive and promising in tissue regeneration. Previously, using one-bead one-compound (OBOC) combinatorial technology, we identified LLP2A, an integrin α4β1 ligand, which had a strong binding to human placenta-derived mesenchymal stem cells (PMSCs). In this study, we isolated PMSCs derived EVs (PMSC-EVs) and demonstrated they expressed integrin α4β1 and could improve endothelial cell (EC) migration and vascular sprouting in an ex vivo rat aortic ring assay. LLP2A treated culture surface significantly improved PMSC-EV attachment, and the PMSC-EV treated culture surface significantly enhanced the expression of angiogenic genes and suppressed apoptotic activity. We then developed an approach to enable “Click chemistry” to immobilize LLP2A onto the surface of electrospun scaffolds as a linker to immobilize PMSC-EVs onto the scaffold. The PMSC-EV modified electrospun scaffolds significantly promoted EC survival and angiogenic gene expression, such as KDR and TIE2, and suppressed the expression of apoptotic markers, such as caspase 9 and caspase 3. Thus, PMSC-EVs hold promising potential to functionalize biomaterial constructs and improve the vascularization and regenerative potential. The EVs modified biomaterial scaffolds can be widely used for different tissue engineering applications.
研究领域:
组织工程
·
生物材料
·
再生医学
·
细胞生物学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2020
·Vol. 45
·期 3
·816-824
·
IF 3.098
Wei,Wang,Hu,Xie,Ling,Gao,Cao
Icaritin, a metabolite of icariin, is a potent promoter of bone marrowderived mesenchymal stem cells (BMSCs) osteogenesis, but the underlying mechanisms remain unclear. To examine the effects of icaritin on osteogenic differentiation, BMSCs were exposed to osteogenic induction medium
with or without icaritin pretreatment in the present study. It was identified that icaritin (0.011 µM) exhibited no cytotoxicity on the proliferative abilities of the BMSCs. Icaritin at 1 µM increased alkaline phosphatase activity, mineral deposition and osteoblastspecific
gene expression. Treatment with 1 µM Icaritin upregulated osteocalcin, RUNX family transcription factor 2, tissuenonspecific alkaline phosphatase and βcatenin, and suppressed sclerostin (SOST) gene expression in different stages of osteogenic differentiation. It was also
demonstrated that SOST overexpression inhibited icaritininduced osteogenesis. The western blot analysis data suggested that ICI 182780, which causes estrogen receptor α (ERα) degradation, reversed the icaritininduced decrease in SOST expression, which was inconsistent
with the results of immunofluorescence analysis. In conclusion, icaritin was demonstrated to promote the osteogenesis of hBMSCs by downregulating SOST expression, and icaritininduced suppression of SOST was regulated in part via the Wnt/βcatenin/ERα axis.
研究领域:
药理学
·
干细胞生物学
·
骨骼生物学
✓ 已验证
DOI
PubMed
高影响因子
PHYSIOLOGICAL RESEARCH
·
2025
·
IF 2
D Zhang,Y Zhang,J Wen,B Wu,Y Chen,Y Song,C Liang
Promoting angiogenesis to enhance the success rate of parathyroid autotransplantation represents an effective strategy for improving patient outcomes following thyroid surgery. Eyes absent homolog 1 (EYA1) may be modulated by stromal vascular fraction (SVF) and adipose-derived stem cells (ADSCs) to facilitate angiogenesis. Phototherapy, which involves the use of artificial light source irradiation for disease prevention and treatment, has emerged as a promising approach. However, it remains unclear whether ADSCs pretreated with phototherapy can promote angiogenesis in the parathyroid gland through the regulation of EYA1. Primary human ADSCs (hADSCs) were isolated and identified. The impact of various wavelengths of light on the proliferation and secretion of angiogenic factors by hADSCs was assessed using a CCK-8 assay and an ELISA. Subsequently, the influence of light-pretreated hADSCs on HUVEC proliferation, migration, and angiogenesis was evaluated through CCK-8, Transwell, tube formation assays, and ELISA. Finally, qRT-PCR and Western blot analysis were employed to examine the effects of different wavelengths of light on the expression levels of differentiation-related transcription factors in hADSCs, including EYA1. To further elucidate the role of EYA1, an EYA1 interference plasmid (si-EYA1) and its negative control plasmid (si-NC) were transfected into hADSCs to determine whether silencing EYA1 would inhibit the promotion of HUVECs migration and angiogenesis by light-pretreated hADSCs. The results demonstrated that compared with green light (516 nm) and blue light (475 nm), red light (635 nm) irradiation significantly enhanced hADSCs proliferation and the secretion of angiogenic factors. Moreover, light-pretreated (red light) hADSCs markedly promoted HUVECs proliferation, migration, and angiogenesis. Additionally, red light irradiation significantly upregulated the mRNA and protein expression of EYA1, SIX1, TGF-beta1, and Wnt1 while downregulating the mRNA and protein expression of DACH1 in hADSCs. However, silencing EYA1 attenuated the promotive effect of light-pretreated hADSCs on HUVECs migration and angiogenesis. These findings suggest that phototherapy-pretreated hADSCs may enhance HUVECs migration and angiogenesis via the activation of EYA1 and increased secretion of angiogenic factors. Key words Phototherapy " Adipose-derived stem cells " Human umbilical vein endothelial cells " Angiogenesis " Migration " Eyes absent homolog 1.
研究领域:
再生医学
·
血管生物学
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干细胞生物学
·
分子生物学
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转化医学
·
光生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Stem Cell Research & Therapy
·
2025
·Vol. 16
·期 1
·1-20
·
IF 7.3
Liu Yonghao,Zhou Heng,Pang Pengcheng,Liu Ye,Situ Jieying,Wang Junnan,He Yan,Ye Qingsong
Background Mesenchymal stem cell exosomes are the most extensively researched type of Extracellular vesicles (EVs) that offer novel avenues for hair regeneration. However, their use in the field of hair regeneration was limited by their poor production of exosomes. It has been discovered that intracellular vesicles (IVs), which are produced at a higher rate than exosomes, play a comparable biological purpose. As a result, we developed HTMI-MN, a microneedle that uses tremella, a type of Tremella polysaccharide (TPS), and hyaluronic acid (HA) as matrix materials. It has magnetic intracellular vesicles (Mag-IVs), which work in concert to treat androgenic alopecia (AGA) and encourage hair growth.Methods After characterization of the Mag-IVs, we evaluated the effect on angiogenesis by scratch assay, angiogenesis assay, Western Blot and ELISA assay. In addition, we tested the protective effect of Human hair papillary cells (HHDPCs) by CCK-8 method, Western Blot and flow cytometry. Finally, the effects of tremella polysaccharide on M1/M2 polarization of macrophages were detected by fluorescence staining, Western Blot and flow cytometry. AGA model was established in vivo by DHT, and treatment was given by microneedle injection.Results Our study found that Mag-IVs have greater power to promote angiogenesis and protect HHDPCs from apoptosis compared to other vesicles. Besides, tremella polysaccharide can make the transformation of macrophages to anti-inflammatory phenotype. Taken together, in vivo experiments showed that hair regeneration was faster in HTMI-MN-treated mice.Conclusion These results indicate that Mag-IVs and tremella polysaccharide can synergistically improve the hair microenvironment, which has a promising future for AGA treatment.
研究领域:
再生医学
·
干细胞研究
·
生物材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Ying Liu,Xinran Wang,Chenrong Jin,Juhui Qiao,Chenxi Wang,Leilei Jiang,Shiting Yu,Daian Pan,Daqing Zhao,Siming Wang,Meichen Liu
Background Disruption of stem cell and microbial homeostasis accelerates the aging process. Hence, maintaining these balances effectively delays aging and alleviates the symptoms of age-related diseases. Recent research indicates that targeting endoplasmic reticulum (ER) stress and immune deficiency (IMD) signalling may play a positive role in maintaining homeostasis in aging intestinal stem cells (ISC) and microbial equilibrium. Previous research has suggested that total ginsenosides (TG) derived from Panax ginseng C. A. Meyer may exhibit potential anti-aging properties by mitigating ER stress and mediating the IMD pathway. Nevertheless, it remains unclear whether TG improve ISC and microbial homeostasis by modulating ER stress and the IMD pathway to promote healthy aging. Purpose To elucidate whether TG promotes healthspan in Drosophila and its underlying molecular mechanisms, focusing on its role in regulating ER stress and the IMD pathway to maintain ISC and intestinal microbiota homeostasis. Methods High performance liquid chromatography was performed to detect the main saponin monomer in TG. Survival rate, gut length, barrier function, and feeding/excretion behaviour assays were used to evaluate the effects of TG on the lifespan and gut health of Drosophila . At the stem cell level, “esg-luciferase” reporter system, esg-GFP/delta stem cell fluorescent labelling, and phospho-histone H3+ mitotic activity assays were employed to determine whether TG prevented natural aging or oxidative stress-associated ISC over-proliferation in Drosophila . Immunofluorescence staining was used to detect the effects of TG on ER stress during aging. Overexpression or interference of ER stress target genes and their related c-Jun N-terminal kinase (JNK) gene was manipulated using gene editing technology to verify the molecular mechanism by which TG maintains age-related ISC proliferation homeostasis. Molecular docking and isothermal titration calorimetry were used to verify the direct interactions between TG and ER stress target genes. In addition, at the intestinal flora level, 16S rDNA sequencing was used to analyse the effect of TG on the diversity and abundance of Drosophila intestinal flora and the possible functional pathways involved. RT-qPCR was performed to determine whether TG mediated the expression of target genes in the IMD pathway. A dominant bacterial species-specific mono-association analysis were performed to verify whether the effects of TG on IMD target genes and ISC proliferation depended on the direct control of the dominant bacterial species. Results Our results suggest that administration of TG delays the decline in gut morphology and function in aging Drosophila . TG prevents age-associated ISC hyperproliferation by inhibiting ER stress IRE1-mediated JNK signaling. Furthermore, oral TG prevented aging-associated ISC and gut microbiota dysbiosis by remodelling the gut microbiota and inhibiting Acetobacter -mediated activation of IMD target genes. Conclusion TG promotes healthy aging by inhibiting the excessive proliferation of ISC and alleviating intestinal microbial imbalance, thereby providing new insights for the research and development of anti-aging TG products.
研究领域:
衰老
·
干细胞生物学
·
微生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）