ACS Omega
·
2019
·
IF 2.584
Yangjie Shao,Dongqi You,Yiting Lou,Jianhua Li,Binbin Ying,Kui Cheng,Wenjian Weng,Huiming Wang,Mengfei Yu,Lingqing Dong
Naringin, a Chinese herbal medicine, has been demonstrated to concentration-dependently promote osteogenic differentiation of mesenchymal stem cells (MSCs). However, it remains a challenge to load naringin on coatings for osteogenesis and further control the release kinetics. Here, we demonstrated that the release behavior of naringin on rutile nanorod films could be controlled by either mixing naringin with gelatin methacryloyl (GelMA) before spinning onto the films or soaking the obtained GelMA-incorporated films with the naringin solution to achieve the distinct degradation-type release and diffusion-type release, respectively. We further revealed that the naringin-loaded coatings facilitated adhesion, proliferation and late differentiation, and mineralization of MSCs. Our findings provided a novel strategy to engineer the coatings with controlled release of naringin and emphasized the bioactivity of naringin for the osteogenic differentiation of MSCs.
研究领域:
生物材料学
·
细胞生物学
·
组织工程学
✓ 已验证
DOI
PubMed
高影响因子
CURRENT GENE THERAPY
·
2018
·
IF 1.943
Li Li-Ming,Huang Ling-Ling,Jiang Xin-Chi,Chen Jia-Chen,OuYang Hong-Wei,Gao Jian-Qing
Introduction: Mesenchymal Stem Cells (MSCs) are promising candidates for nerve tissue engineering. Brain Derived Neurotrophic Factor (BDNF) secreted by MSCs can function to increase neural differentiation and relieve inflammation response. Gene transfection technology is an efficient
strategy to increase the secretion levels of cytokines and enhance cellular functions. However, transfection and in vivo gene expression of environmentally sensitive stem cells have been one of the most challenging subjects due to the requirement in both safety and transfection efficiency.
In this study, gene transfection technology was applied to prepare BDNF gene recombinant MSCs based on our previously reported liposomal vector ScreenFect® A. To improve cellular survival and gene expression after in situ implantation of MSCs, an adhesive peptide modified hydrogel scaffold
was constructed using hyaluronic acid. The scaffold was optimized and modified with an adhesive peptide PPFLMLLKGSTR. The transfected MSCs exhibited improved cellular survival and sustained gene expression in the three-Dimentional (3D) scaffold in vitro. Compared to untransfected MSCs, gene
recombinant MSCs effectively improved spinal tissue integrity, inhibited glial scar formation and alleviated inflammatory response. These effects were found discounted when cells were implanted without the scaffold. Conclusion: The study developed a promising implantation system for therapy
of severe spinal cord injury and provided the first understanding of Screenfect® A about its functions on stem cell therapy for nerve tissue repair as well as three-dimentional gene expression.
研究领域:
干细胞治疗
·
组织工程
·
神经科学
·
基因治疗
✓ 已验证
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Shuai Liu,Peili Li,Xin Liu,Penghui Wang,Wenliang Xue,Yanhan Ren,Rong Yang,Bo Chi,Zhiwen Ye
Aiming at the difficulty of integrated repair of osteochondral tissue, we designed a hybrid hydrogel scaffold that mimicked the microenvironment of osteochondral niches. Besides, the nano-hydroxyapatite (nHAP) was specially introduced into the hydrogel for its natural ability to promote bone regeneration. The hydrogel also exhibited good toughness (7500 KJ/m 3 ), strength (1000 kPa), viscoelasticity, and in vitro cell experiments showed that hydrogels had quite good cytocompatibility (near 100 % viability). The results of the three-dimensional (3D) cell culture also proved that the survival rate of the cells in the hybrid hydrogels doped with nHAP and dispersion were the highest. In vitro RT-qPCR experiments proved that after being cultured in hydrogel scaffolds doped with nHAP, bone mesenchymal stem cells (BMSCs) could express genes related to osteoblasts and chondrocytes. As a result, this hydrogel provides a general for developing alternative materials applicable for stem cells differentiation and even osteochondral tissue engineering.
研究领域:
生物材料
·
组织工程
·
干细胞生物学
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
POLYMER
·
2023
·
IF 4.6
Xiaoqiong Wang,Leisha Cui,Jing Hong,Zhaojun Wang,Jiawei Li,Zhongqing Liu,Zhanchi Zhu,Ying Hao,Guosheng Cheng,Junhong Jiang
Because of the shortage of donors, alveolar stem cells transplantation is under development as an important and promising treatment for end-stage lung disease. Currently, the acquisition of functional lung cells is mostly performed by two dimensional (2D) culture and suffers from low directed differentiation efficiency. It is particularly critical to replicate the three dimensional (3D) growth of lung cells, as cells grow in 3D microenvironment in vivo . In this work, we develop a 3D biomimetic composite hydrogel system based on the in situ crosslinking of the synthetic polymer 4 arm acrylated-poly(ethylene glycol) (4PEG-AC), the thiolated natural polymer hyaluronic acid (HA-SH), and the thiolated polypeptide (GSE4-SH) via a Michael-type “click” reaction under physiological conditions at pH 7.8. The PEG/HA/GSE4 hydrogel with a sheer modulus of 104.1 ± 9.9 Pa was used for 3D growth of bone marrow mesenchymal stem cells (BMSCs), displaying excellent biocompatibility. Covalent conjugation of GSE4 peptide in hydrogel promoted the differentiation of BMSCs into alveolar epithelial type 2 cells (AEC2s) with a AEC2s-differentiation rate of 58.6 ± 3.3%. Overall, this study provides a suitable 3D biomimetic platform to enable the efficient differentiation of stem cells into lung cells for lung tissue engineering.
研究领域:
组织工程
·
干细胞生物学
·
生物材料
·
肺再生
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
·
2018
·
IF 3.247
Chao Zhong,Zhenhuang Chen,Xiaocui Luo,Cuicui Wang,Hui Jiang,Jianzhong Shao,Minxin Guan,Liquan Huang,Xiao Huang,Jinfu Wang
Inner ear hair cells are mechanoreceptors responsible for hearing. Pathogenic defects of hair cell-specific genes are one of the major causes of deafness. The BarH class homeobox gene Barhl1 is a deafness gene expressed in developing hair cells, yet the role of Barhl1 during hair cell development remains poorly understood. In the present study, we first established an in vitro differentiation system to efficiently obtain mouse embryonic stem cell (mESC)-derived hair cell-like cells. Subsequently, a mESC line carrying a targeted disruption of Barhl1 was generated using CRISPR/Cas9 technology and subjected to the established in vitro hair cell differentiation protocol. Targeted disruption of Barhl1 does not affect the induction of mESCs toward early primitive ectoderm-like (EPL) cells and otic progenitors but strongly inhibits the differentiation of hair cell-like cells. Using RNA-sequencing and bioinformatics, we further unravel the molecular mechanism underlying Barhl1 -mediated hair cell development. Our data demonstrate the essential role of Barhl1 during hair cell development and provide a basis for the treatment of Barhl1 mutation-based deafness.
研究领域:
发育生物学
·
干细胞研究
·
基因组学
·
听觉科学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Javad Harati,Xuelian Tao,Hosein Shahsavarani,Ping Du,Massimiliano Galluzzi,Kun Liu,Zhen Zhang,Peter Shaw,Mohammad Ali Shokrgozar,Haobo Pan,Peng-Yuan Wang
Polydopamine (PDA) is a biocompatible cell-adhesive polymer with versatile applications in biomedical devices. Previous studies have shown that PDA coating could improve cell adhesion and differentiation of human mesenchymal stem cells (hMSCs). However, there is still a knowledge gap in the effect of PDA-mediated protein adsorption on the epigenetic status of MSCs. This work used gelatin-coated cell culture surfaces with and without PDA underlayer (Gel and PDA-Gel) to culture and differentiate primary human adipose-derived stem cells (hASCs). The properties of these two substrates were significantly different, which, in combination with a variation in extracellular matrix (ECM) protein bioactivity, regulated cell adhesion and migration. hASCs reduced focal adhesions by downregulating the expression of integrins such as αV, α1, α2, and β1 on the PDA-Gel compared to the Gel substrate. Interestingly, the ratio of H3K27me3 to H3K27me3+H3K4me3 was decreased, but this only occurred for upregulation of AGG and BMP4 genes during chondrogenic differentiation. This result implies that the PDA-Gel surface positively affects the chondrogenic, but not adipogenic and osteogenic, differentiation. In conclusion, for the first time, this study demonstrates the sequential effects of PDA coating on the biophysical property of adsorbed protein and then focal adhesions and differentiation of hMSCs through epigenetic regulation. This study sheds light on PDA-mediated mechanotransduction.
研究领域:
生物医学工程
·
干细胞生物学
·
组织工程
·
表观遗传学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Nanomaterials
·
2022
·
IF 3.791
Yifan Wang,Xin Wu,Wenjing Yang,Pei Feng,Wei Tan,Youwen Deng,Cijun Shuai
Magnesium ion (Mg2+)-based materials are known to exert osteogenic effects that can be enhanced by the bioelectrical properties of magnetic fields. In this study, we examined the effect of a medium-strength static magnetic field (SMF), combined with a Mg2+-containing medium, on the proliferation and osteogenic differentiation of mouse bone marrow mesenchymal stem cells (BMSCs). Mouse BMSCs were divided into a control group, 7.5 mM Mg2+ group, 15 mT SMF group, and 7.5 mM Mg2+ plus 15 mT SMF group. Osteoblast proliferation was measured using a Cell Counting Kit-8 assay, whereas osteogenic differentiation was detected using alkaline phosphatase (ALP) staining and western blot analysis, respectively. The number and size of calcium nodules were determined using Alizarin Red staining. Compared with those in the control group, the ALP activity, calcium nodule formation, and osteogenic protein expression were promoted in other groups. In particular, Mg2+-SMF had a significant effect after 7 days of intervention and more effectively promoted BMSC differentiation and proliferation than either Mg2+ or the SMF alone, suggesting that Mg2+-SMF synergistically contributed to osteogenic differentiation and cell proliferation. To examine their roles in bone differentiation, the Magt1 and Creb1 genes were silenced in BMSCs, and the findings indicated that the synergistic intervention with Mg2+ and magnetic fields might exert osteogenic effects via the MAGT1 channel and CREB1 protein. This study provides an experimental basis for a potential Mg2+-SMF synergistic artificial bone material that could be clinically applied in the treatment of bone defects.
研究领域:
生物医学工程
·
干细胞生物学
·
骨科
·
材料科学
✓ 已验证
DOI
高影响因子
Nanoscale
·
2020
·Vol. 12
·期 18
·10106-10116
·
IF 6.895
Kaipeng Wang,Qian Wu,Xichao Wang,Guohai Liang,Anli Yang,Jinming Li
Finding a method to control and detect the differentiation of stem cells in real time remains a challenge for regenerative medicine. Here we developed the multifunctional upconversion nanoparticle (UCNP) approach for both near-infrared (NIR) control and the real-time detection of osteogenic differentiation in mesenchymal stem cells (MSCs). We first synthesized Tm/Er doped core–shell UCNPs (NaYF4:Yb/Tm/Er@NaYF4), and the core–shell UCNPs were coated with mesoporous silica for drug loading and installing photomechanical azobenzene (azo). Then the Arg-Gly-Asp (RGD) peptide and the matrix metalloproteinase 13 (MMP13) sensitive peptide-black hole quencher-3 group (CGPLGVRGK-BHQ-3) were conjugated on the surface of UCNPs for cell targeting and detection of cell differentiation. The final multifunctional UCNPs are called UCNP@mSiO2-azo-peptide-BHQ-3. The drug icariin (ICA), which can induce the osteogenic differentiation of MSCs, was loaded into UCNP@mSiO2-azo-peptide-BHQ-3 to form the UCNP nanocomplexes. ICA could be released from UCNP nanocomplexes in a NIR-controlled manner that is based on the transformation of the trans-isomer of azo into the cis isomer under the upconverted UV and visible light. Meanwhile, UCNP@mSiO2-azo-peptide-BHQ-3 could also be used as a nanoprobe to detect the activity of the MMP13 enzyme by enzyme digestion and UCNP fluorescence recovery. By detecting MMP13, which is produced by osteogenic differentiation, a real-time detection of cell differentiation in living differentiated MSCs could be achieved using UCNP nanoprobes. Thus, the multifunctional UCNPs combined the control of cell differentiation with the real-time detection of cell differentiation in MSCs, which makes them a powerful tool for regulating and detecting the differentiation of MSCs in regenerative medicine.
研究领域:
再生医学
·
纳米技术
·
干细胞生物学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Nanoscale
·
2015
·Vol. 8
·期 4
·1897-1904
·
IF 7.394
Weibo Guo,Shu Wang,Xin Yu,Jichuan Qiu,Jianhua Li,Wei Tang,Zhou Li,Xiaoning Mou,Hong Liu,Zhonglin Wang
The cell–material interface is one of the most important considerations in designing a high-performance tissue engineering scaffold because the surface of the scaffold can determine the fate of stem cells. A conductive surface is required for a scaffold to direct stem cells toward neural differentiation. However, most conductive polymers are toxic and not amenable to biological degradation, which restricts the design of neural tissue engineering scaffolds. In this study, we used a bioactive three-dimensional (3D) porcine acellular dermal matrix (PADM), which is mainly composed of type I collagen, as a basic material and successfully assembled a layer of reduced graphene oxide (rGO) nanosheets on the surface of the PADM channels to obtain a porous 3D, biodegradable, conductive and biocompatible PADM–rGO hybrid neural tissue engineering scaffold. Compared with the PADM scaffold, assembling the rGO into the scaffold did not induce a significant change in the microstructure but endowed the PADM–rGO hybrid scaffold with good conductivity. A comparison of the neural differentiation of rat bone-marrow-derived mesenchymal stem cells (MSCs) was performed by culturing the MSCs on PADM and PADM–rGO scaffolds in neuronal culture medium, followed by the determination of gene expression and immunofluorescence staining. The results of both the gene expression and protein level assessments suggest that the rGO-assembled PADM scaffold may promote the differentiation of MSCs into neuronal cells with higher protein and gene expression levels after 7 days under neural differentiation conditions. This study demonstrated that the PADM–rGO hybrid scaffold is a promising scaffold for neural tissue engineering; this scaffold can not only support the growth of MSCs at a high proliferation rate but also enhance the differentiation of MSCs into neural cells.
研究领域:
组织工程
·
神经科学
·
生物材料科学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF BIOACTIVE AND COMPATIBLE POLYMERS
·
2019
·
IF 1.976
Zengjie Fan,Yingying Nie,Zizi Chen,Xuzhuzi Xie,Xiaozhu Liao,Yuan Wei
Temperature-responsive hydrogel culture system is considered as an ideal platform for cell sheet harvest, but its complex preparation methods and harsh reaction conditions limit its application. Inspired by the marine mussels, a biomimetic method presented here is to construct a novel temperature-responsive hydrogel culture system for stem cell sheet harvest. The tissue culture polystyrene is first modified with polydopamine coating, and then amine-terminated poly(N-isopropylacrylamide) is grafted onto the coating via the Schiff base or Michael addition reaction to construct the temperature-sensitive hydrogel culture system. Then, bone marrow stromal cells are cultured on the culture system to construct cell sheets. The prepared culture system shows significant temperature-sensitive property with the grafted concentrations of poly(N-isopropylacrylamide) ranging from 0.5 to 1 g/L. Meanwhile, the constructed culture system has low cytotoxicity and facilitates the stem cell adhesion, proliferation, and cell sheet formation at 37°C. When the culture system is placed in a 20°C environment, the cell sheet can be completely detached from the surface of tissue culture polystyrene without being treated with any enzymes. More importantly, the cell morphology, cell sheet thickness, and the fibril structure of the associated proteins are similar to the cells cultured on the tissue culture polystyrene without modification. The biomimetic, simple, inexpensive, and environmentally friendly preparation of the culture system enables it to be used for the harvest of cell sheet and even applied to tissue engineering for tissue regeneration.
研究领域:
材料科学
·
生物材料
·
组织工程
·
细胞生物学
✓ 已验证
DOI
高影响因子
Cell Reports
·
2022
·
IF 9.995
Ruipeng Zhuge,Chao Wang,Jie Wang,Shuyu Yu,Liming Liao,Xiaofeng Zheng
Summary YAP1 functions in lineage differentiation of pluripotent embryonic stem cells (ESCs); however, the detailed mechanisms underlying the regulation of YAP1 activity during ESC differentiation remain elusive. Here, we report that hCINAP serves as a negative regulator of YAP1 during ESC fate decisions. The expression of mCINAP, the murine homolog of hCINAP, is downregulated during the differentiation process of murine ESC (mESC) ectoderm lineage, leading to liquid-liquid phase separation (LLPS) of NEDD4 and activation of YAP1. Mechanistically, hCINAP interacts with and prevents NEDD4 from forming cytoplasmic condensates that compartmentalize YAP1 and its kinase NLK, facilitating YAP1 phosphorylation at Ser128 and promoting YAP1 activation. mCINAP depletion leads to the formation of NEDD4 condensates and YAP1 activation, which impedes endoderm differentiation of mESCs. Our study shows that hCINAP is a vital regulator of YAP1 activity and is essential for stem cell fate decisions, which provides mechanistic insight into early embryogenesis.
研究领域:
干细胞生物学
·
细胞信号传导
·
发育生物学
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2021
·
IF 6.4
Xiao Han,Shijia Tang,Lin Wang,Xueqin Xu,Ruhan Yan,Sen Yan,Zhaobin Guo,Ke Hu,Tingting Yu,Mengping Li,Yuqin Li,Feimin Zhang,Ning Gu
Introduction Promotion odontogenic differentiation of dental pulp stem cells (DPSCs) is essential for dentin regeneration. Physical cellular microenvironment is of critical importance for stem cells differentiation and influences the function of other biological/chemical factors to differentiation. Methods Based on adjusting the mechanical/interfacial properties of hydrogels, multicellular spheroids (MCSs) of DPSCs generated through self-organization. The spheroids were characterized by immunofluorescent staining and flow cytometry. Quantitative real-time polymerase chain reaction, alkaline phosphatase (ALP) activity assay, ALP staining and Alizarin Red S staining were performed to evaluate the osteogenic/odontogenic differentiation of DPSCs with or without magnetic iron oxide nanoparticles (IONPs) induction. Results MCSs of DPSCs exhibited a significant upregulation of E-cadherin and N-cadherin and enriched CD146 positive subpopulation, along with a stronger osteogenic/odontogenic differentiation ability. Moreover, DPSCs spheroids showed more substantial osteogenic differentiation tendency than the classical two-dimensional cultured DPSCs under the stimulation of magnetic IONPs. Conclusion Three-dimensional spheroids culture of DPSCs based on composite viscoelastic materials combined with mechanical/magnetic stimulation may provide a theoretical basis for the subsequent development of dentin or bone regeneration technology.
研究领域:
组织工程
·
干细胞生物学
·
生物材料
·
再生医学
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）