International Journal of Nanomedicine
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2021
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IF 6.4
Guoxin Jing,Kun Li,Feiyue Sun,Jintong Niu,Rongrong Zhu,Yechang Qian,Shilong Wang
Introduction Embryonic stem cells (ESCs) possess great application prospects in biological research and regenerative medicine, so it is important to obtain ESCs with excellent and stable cellular states during in vitro expansion. The feeder layer culture system with the addition of leukemia inhibitory factor (LIF) is currently applied in ESC cultures, but it has a series of disadvantages that could influence the culture efficiency and quality of the ESCs. With the development of nanotechnology, many studies have applied nanomaterials to optimize the stem cell culture system and regulate the fate of stem cells. In this study, we investigated the layer-number-dependent biofunction of graphene oxide (GO) on the pluripotency of ESCs from mice (mESCs). Methods Single-layer GO (SGO) and multi-layer GO (MGO) were characterized and their effects on the cytotoxicity and self-renewal of mESCs were detected in vitro. The differentiation potentials of mESCs were identified through the formation of embryoid bodies and teratomas. The regulatory mechanism of GO was verified by blocking the target receptors on the surface of mESCs using antibodies. Results Both SGO and MGO were biocompatible with mESCs, but only MGO effectively sustained their self-renewal and differentiation potential. In addition, GO influenced the cellular activities of mESCs by regulating the interactions between extracellular matrix proteins and integrins. Conclusion This work demonstrates the layer-number-dependent effects of GO on regulating the cell behavior of mESCs and reveals the extracellular regulatory mechanism of this process.
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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细胞工程
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产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2023
·
IF 5.7
Xiaoxue Ren,Xiaoting Gao,Yicheng Cheng,Lingxia Xie,Liping Tong,Wei Li,Paul K. Chu,Huaiyu Wang
Mesenchymal stem cells (MSCs), with high self-renewal ability and multipotency, are commonly used as the seed cells for tissue engineering. However, the reduction and loss of multipotential ability after necessary expansion in vitro set up a heavy obstacle to the clinical application of MSCs. Here in this study, we exploit the autologous crystallization ability of biocompatible poly (ε-caprolactone) (PCL) to obtain uniformly distributed nanoneedle arrays. By controlling the molecular weight of PCL, nanoneedle with a width of 2 μm and height of 50 nm, 80 nm, and 100 nm can be successfully fabricated. After surface chemical modification with polydopamine (PDA), the water contact angle of the fabricated PCL nanoneedle arrays are reduced from 84° to almost 60° with no significant change of the nanostructure. All the fabricated substrates are cultured with bone marrow MSCs (BMMSCs), and the adhesion, spreading, proliferation ability and multipotency of cells on different substrates are investigated. Compared with the BMMSCs cultured on pure PCL nanoneedle arrays, the decoration of PDA can improve the adhesion and spreading of cells and further change them from aggregated distribution to laminar distribution. Nevertheless, the laminar distribution of cultured cells leads to a weak cell-cell interaction, and hence the multipotency of BMMSCs cultured on the PCL-PDA substrates is decimated. On the contrary, the pure PCL nanoneedle arrays can be used to maintain the multipotency of BMMSCs via clustered growth, and the PCL1 nanoneedle array with a height of 50 nm is more promising than the other 2 with regard to the highest proliferation rate and best multipotential differentiation ability of cultured cells. Interestingly, there is a positive correlation between the strength of cell-cell interaction and the multipotency of stem cells in vitro . In conclusion, we have successfully maintained the multipotency of BMMSCs by using the PCL nanoneedle arrays, especially the PCL1 nanoneedle array with a height of 50 nm, as the substrates for in vitro extension, and further revealed the importance of cell-cell interaction on the multipotency of MSCs. The study provides a theoretical basis for the behavioral regulation of MSCs, and is instructive to the design of tissue engineering scaffolds.
研究领域:
组织工程
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干细胞生物学
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材料科学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2023
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IF 5.7
Yang Kuan,Wei Wei,Gao Li Ting,Zhao Xin Yi,Liu Zhenqi,Li Jianhui,Li Haopeng,Miyatake Hideyuki,Ito Yoshihiro,Chen Yong Mei
The proper microenvironment is critical for the storage and transportation of embryonic stem cells (ESCs). To mimic a dynamic 3D microenvironment as it exists in vivo and consider “off-the-shelf” availability reaching the destination, we proposed an alternative approach that allows for facile storage and transportation of stem cells in the form of ESCs-dynamic hydrogel construct (CDHC) under ambient conditions. To form CDHC, mouse embryonic stem cells (mESCs) were in-situ encapsulated within a polysaccharide-based dynamic and self-biodegradable hydrogel. After storing CDHC in a sterile and hermetic environment for 3 days and then transferring to a sealed vessel with fresh medium for another 3 days, the large and compact colonies retained a 90% survival rate and pluripotency. Furthermore, after transporting and arriving at the destination, the encapsulated stem cell could be automatically released from the self-biodegradable hydrogel. After continuous cultivation of 15 generations of retrieved cells, automatically released from the CDHC, the mESCs underwent 3D encapsulation, storage, transportation, release, and continuous long-term subculture; resumed colony forming capacity and pluripotency were revealed by stem cell markers both in protein and mRNA levels. We believe that the dynamic and self-biodegradable hydrogel provides a simple, cost-effective, and valuable tool for storing and transporting “ready-to-use” CDHC under ambient conditions, facilitating “off-the-shelf” availability and widespread applications.
研究领域:
生物材料
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干细胞生物学
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组织工程
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生物技术
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-16
·
IF 15.7
Wang Ran,Qi Yilin,Liu Jinjin,Li Yang,An Hongde,Wang Heping,Song Jie,Hu Wenzhuo,Wu Shaochun,Yu Leqian,Chen Yao,Xue Xue
Embryonic stem cells (ESC) are pluripotent, with the potential to differentiate into multiple cell types, making them a valuable tool for regenerative medicine and disease therapy. However, common culture methods face challenges, including strict operating procedures and high costs. Currently, Leukemia inhibitory factor (LIF), an indispensable bioactive protein for ESC culture, is typically applied to maintain self-renewal and pluripotency, but its instability and high cost limit its effectiveness in stable culture conditions. Hence, we have developed an innovative strategy using a soluble nanomaterial, metal-organic polyhedra (MOPs), to effectively maintain the self-renewal and pluripotency of ESC. The selected amino-modified vanadium-based MOP not only exhibits excellent biocompatibility and high stability but also possesses similar or even superior biological functions compared to commercial LIF. Due to the precise structure of MOPs, the active site responsible for maintaining ESC pluripotency has been identified and regulated at the molecular level. The new ESC culture method significantly reduces costs, simplifies preparation, and enhances the practicality of biopharmaceutical preparation and storage. This represents the first case of using MOPs to maintain self-renewal of ECS, opening an avenue for introducing advanced materials into the development of innovative ESC culture methods.
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产品关联
DOI
PubMed
高影响因子
Human Cell
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2024
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IF 3.4
Chen Die,Su Jimei,Huang Xueying,Chen Hongyu,Jiang Tiejia,Zhi Chunchun,Zhou Zuolin,Zhang Bing,Yu Lan,Jiang Xiaoling
Pathogenic variants of the KCNH1 gene can cause dominant-inherited Temple–Baraitser/Zimmermann–Laband syndrome with severe mental retardation, seizure, gingival hyperplasia and nail hypoplasia. This study established an induced pluripotent stem cell (iPSC) line using urinary cells from a girl with KCNH1 recurrent/hotspot pathogenic variant c.1070G > A (p.R357Q). The cell identity, pluripotency, karyotypic integrity, absence of reprogramming virus and mycoplasma contamination, and differential potential to three germ layers of the iPSC line, named as ZJUCHi003, were characterized and confirmed. Furthermore, ZJUCHi003-derived neurons manifested slower action potential repolarization process and wider action potential half-width than the normal neurons. This cell line will be useful for investigating the pathogenic mechanisms of KCNH1 variants-associated symptoms, as well as for evaluating novel therapeutic approaches.
研究领域:
干细胞生物学
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遗传学
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神经科学
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DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
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2018
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IF 1.911
Qianqian Wei,Jiachang Jin,Xinyuan Wang,Qijun Shen,Mi Zhou,Shizhong Bu,Yabin Zhu
Polyurethane (PU) is a class of polymers that have been applied for tissue-engineering scaffolds. Cross-linked poly(ester urethane) (CPU), synthesized with ferric catalyst in our laboratory, was modified by silk fibroin (SF) grafting using our aminolysis and glutaradehyde crosslinking method. The physical and chemical properties of the materials were investigated by scanning electron microscope (SEM), atomic force microscope (AFM) and tensile tester. The results showed that SF grafted CPU possessed good strain and strength (4.29 ± 0.18 MPa/382.38 ± 0.71%). Its surface chemistry and roughness were fine to well support the growth of bone marrow mesenchymal stem cells (BMSC). The cells were verified to maintain the pluripotency after they were cultured in vitro for 2 weeks, which supplied us a good technology to keep cell’s stemness but proliferate cell’s number. These results are valuable for us to further study esophageal tissue engineering with BMSC and polyurethane materials as the components.
研究领域:
材料科学
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生物材料
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组织工程
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干细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
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2024
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IF 6.1
Jing Hong,Zhanchi Zhu,Leisha Cui,Zhaojun Wang,Ying Hao,Xiaopeng Tian,Guosheng Cheng
Hematopoietic stem cell (HSC) expansion offers a key strategy to address the source limitation and donor shortages of HSCs for the treatment of various blood disorders. Specific remodeling of the complex bone marrow microenvironment that contributes to efficient in vitro expansion of HSCs remains challenging. Here, inspired by the regions with different stiffness levels in the bone marrow niche, a three dimensional (3D) bone marrow-mimicking composite scaffold created based on gelatin–hyaluronic acid (Gel–HA) hydrogels and graphene foams (GFs) was engineered to support the in vitro expansion of HSCs. The composite scaffold was prepared by forming a photo-cross-linked Gel–HA hydrogel surrounding the GF. The “soft” Gel–HA hydrogel and “stiff” GF replicate the structure and stiffness of the vascular niche and endosteal niche in the bone marrow, respectively. Furthermore, HSCs cultured in the Gel–HA/GF scaffold proliferated well and retained the CD34+CD38− immunophenotype and pluripotency, suggesting that the Gel–HA/GF composite scaffold supported the in vitro expansion of HSCs, maintaining the primitive phenotype and the ability to differentiate into functional blood cells. Thus, the hydrogel/graphene composite scaffold offers a means of facilitating HSC expansion through structurally and mechanically mimicking bone marrow niches, demonstrating great promise for HSC transplantation.
研究领域:
生物材料
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组织工程
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干细胞生物学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
THERIOGENOLOGY
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2024
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IF 2.4
Xiu-Li Zhang,Zhi-Yong An,Gao-Jie Lu,Tuo Zhang,Cheng-Wei Liu,Meng-Qi Liu,Qing-Xin Wei,Lin-Hu Quan,Jin-Dan Kang
Oocytes and embryos are highly sensitive to environmental stress in vivo and in vitro. During in vitro culture, many stressful conditions can affect embryo quality and viability, leading to adverse clinical outcomes such as abortion and congenital abnormalities. In this study, we found that valeric acid (VA) increased the mitochondrial membrane potential and ATP content, decreased the level of reactive oxygen species that the mitochondria generate, and thus improved mitochondrial function during early embryonic development in pigs. VA decreased expression of the autophagy-related factors LC3B and BECLIN1 . Interestingly, VA inhibited expression of autophagy-associated phosphorylation-adenosine monophosphate-activated protein kinase (p-AMPK), phosphorylation-UNC-51-like autophagy-activated kinase 1 (p-ULK1, Ser555), and ATG13, which reduced apoptosis. Short-chain fatty acids (SCFAs) can signal through G-protein-coupled receptors on the cell membrane or enter the cell directly through transporters. We further show that the monocarboxylate transporter 1 (MCT1) was necessary for the effects of VA on embryo quality, which provides a new molecular perspective of the pathway by which SCFAs affect embryos. Importantly, VA significantly inhibited the AMPK-ULK1 autophagic signaling pathway through MCT1, decreased apoptosis, increased expression of embryonic pluripotency genes, and improved embryo quality.
研究领域:
生殖生物学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2018
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IF 8.806
Guoxin Jing,Zhaojie Wang,Xizhen Zhuang,Xiaolie He,Huijun Wu,Qingxiu Wang,Liming Cheng,Zhongmin Liu,Shilong Wang,Rongrong Zhu
Graphene oxide (GO), with good hydrophilicity and biocompatibility, is widely explored as a carrier for various factors in the field of stem cell differentiation . However, its function of sustaining the stemness of mouse embryonic stem cells (mESCs) and the underlying mechanisms of this process remains undiscovered. Herein, we explored the biofunction of GO on mESCs and revealed the involved signaling pathways and key gene. The alkaline phosphatase activity detection, pluripotency genes quantification and the teratomas formation in vivo confirmed that GO nanosheets could sustain the self-renewal ability of mESCs instead of influencing its pluripotency . The underlying signaling pathways were uncovered by RNA-seq that integrin signaling pathway was involved in the biofunction of GO on mESCs and Vinculin turned to be a key gene for the effect of GO. Further experiments confirmed that the downregulation of Vinculin influenced the fate of mESCs through decreasing the expression of MEK1. Altogether, the study demonstrated for the first time that GOs hold the potential in sustaining the self-renewal of mESCs and clarified the mechanism of this function, which make it play a new role in stem cell research and regenerative medicine .
研究领域:
干细胞生物学
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纳米技术
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再生医学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
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2016
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IF 8.387
Ping Zhou,Fujian Wu,Tiancheng Zhou,Xiujuan Cai,Siqi Zhang,Xiaohong Zhang,Qiuhong Li,Yongliang Li,Yunfei Zheng,Mengke Wang,Feng Lan,Guangjin Pan,Duanqing Pei,Shicheng Wei
Human pluripotent stem cells (hPSCs) possess great value in the aspect of cellular therapies due to its self-renewal and potential to differentiate into all somatic cell types. A few defined synthetic surfaces such as polymers and adhesive biological materials conjugated substrata were established for the self-renewal of hPSCs. However, none of them was effective in the generation of human induced pluripotent stem cells (hiPSCs) and long-term maintenance of multiple hPSCs, and most of them required complicated manufacturing processes . Polydopamine has good biocompatibility , is able to form a stable film on nearly all solid substrates surface , and can immobilize adhesive biomolecules . In this manuscript, a polydopamine-mediated surface was developed, which not only supported the reprogramming of human somatic cells into hiPSCs under defined conditions, but also sustained the growth of hiPSCs on diverse substrates. Moreover, the proliferation and pluripotency of hPSCs cultured on the surface were comparable to Matrigel for more than 20 passages. Besides, hPSCs were able to differentiate to cardiomyocytes and neural cells on the surface. This polydopamine-based synthetic surface represents a chemically-defined surface extensively applicable both for fundamental research and cell therapies of hPSCs.
研究领域:
干细胞研究
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再生医学
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生物材料科学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2014
·Vol. 6
·期 12
·6959-6969
·
IF 6.739
Zhonglin Lyu,Hongwei Wang,Yanyun Wang,Kaiguo Ding,Huan Liu,Lin Yuan,Xiujuan Shi,Mengmeng Wang,Yanwei Wang,Hong Chen
Efficient control of the self-renewal and pluripotency maintenance of embryonic stem cell (ESC) is a prerequisite for translating stem cell technologies to clinical applications. Surface topography is one of the most important factors that regulates cell behaviors. In the present study, micro/nano topographical structures composed of a gold nanoparticle layer (GNPL) with nano-, sub-micro-, and microscale surface roughnesses were used to study the roles of these structures in regulating the behaviors of mouse ESCs (mESCs) under feeder-free conditions. The distinctive results from Oct-4 immunofluorescence staining and quantitative real-time polymerase chain reaction (qPCR) demonstrate that nanoscale and low sub-microscale surface roughnesses (Rq less than 392 nm) are conducive to the long-term maintenance of mESC pluripotency, while high sub-microscale and microscale surface roughnesses (Rq greater than 573 nm) result in a significant loss of mESC pluripotency and a faster undirectional differentiation, particularly in long-term culture. Moreover, the likely signalling cascades engaged in the topological sensing of mESCs were investigated and their role in affecting the maintenance of the long-term cell pluripotency was discussed by analyzing the expression of proteins related to E-cadherin mediated cell–cell adhesions and integrin-mediated focal adhesions (FAs). Additionally, the conclusions from MTT, cell morphology staining and alkaline phosphatase (ALP) activity assays show that the surface roughness can provide a potent regulatory signal for various mESC behaviors, including cell attachment, proliferation and osteoinduction.
研究领域:
干细胞生物学
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纳米技术
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细胞工程
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生物材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
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2017
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IF 5.246
Yi Deng,Yuanyi Yang,Shicheng Wei
Realization of clinical potential of human pluripotent stem cells (hPSCs) in bone regenerative medicine requires development of simple and safe biomaterials for expansion of hPSCs followed by directing their lineage commitment to osteoblasts. In the present study, a chemically defined peptide-decorated polycaprolactone (PCL) nanofibrous microenvironment was prepared through electrospinning technology and subsequent conjugation with vitronectin peptide to promote the culture and osteogenic potential of hPSCs in vitro. The results indicated that hPSCs successfully proliferated and maintained their pluripotency on the biointerface of peptide-conjugated nanofibers without Matrigel under defined conditions. Moreover, the prepared niche exhibited an appealing ability in promoting directed differentiation of hPSCs to osteoblastic phenotype without embryoid body formation step, determined from the cell morphological alteration, alkaline phosphate activity, and osteogenesis-related gene expression, as well as protein production. Such well-defined, xeno-free, and safe nanofiber scaffolds that allow the survival and facilitate osteo-differentiation of hPSCs provide a novel platform for hPSCs differentiation via cell-nanofiber interplay, and possess great value in accelerating the translational perspectives of hPSCs in bone tissue engineering.
研究领域:
干细胞生物学
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组织工程
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生物材料科学
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再生医学
✓ 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）