JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Yue Tang,Yueyue Kang,Xinru Zhang,Caiyi Cheng
Oxidative stress-induced retinal pigment epithelial (RPE) cell damage is a major factor in the pathogenesis of dry age-related macular degeneration (AMD). Although the therapeutic effect of mesenchymal stem cell (MSC) exosomes on dry AMD has been preliminarily discussed, the underlying mechanism has yet to be reported. Here, we demonstrate that MSC exosomes, acting as a nanodrug, can effectively reduce the incidence of dry AMD by regulating Nrf2/Keap1 signaling pathway. In the in vitro study, MSC exosomes relieved the damage of ARPE-19 cells, suppressed the activity of lactate dehydrogenase (LDH), decreased the level of reactive oxygen species (ROS) and upregulated the activity of superoxide dismutase (SOD). In the in vivo study, MSC exosomes were administered via intravitreal injection. MSC exosomes effectively protected RPE layer, photoreceptor outer segment/inner segment (OS/IS) layer and outer nuclear layer (ONL) from NaIO 3 -induced damage. Western blotting results showed that the ratio of Bcl-2/Bax was increased after pre-administration of MSC exosomes in both in vitro and in vivo studies. Moreover, MSC exosomes were found to upregulate the expressions of Nrf2, P-Nrf2, Keap1 and HO-1, while the antioxidant effect of MSC exosomes was blocked by ML385 (a Nrf2 inhibitor). Besides, immunofluorescence results showed that MSC exosomes upregulated the expression of P-Nrf2 in the nucleus compared to the oxidant group. These results indicate that MSC exosomes protect RPE cells from oxidative damage by regulating Nrf2/Kepa1 signaling pathway. In conclusion, MSC exosomes are promising nanotherapeutics for the treatment of dry AMD.
研究领域:
眼科学
·
干细胞生物学
·
分子生物学
·
细胞生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
Tissue Engineering Part A
·
2023
·
IF 4.1
Dr. Shujuan Guo,Mr. Weiguang Li,Prof. Weidong Tian,Prof. Yafei Wu
Periodontium is the rally of soft and hard tissues, which will be devastated continuously by the compromise of periodontitis. Current periodontal therapeutic methods cannot effectively reconstruct periodontal ligament (PDL), which is oriented at an angle with tooth root and combined hard tissues to form cementum-periodontal ligament-alveolar bone complex. Hence, it is urgent to find new techniques for PDL reconstruction to achieve functional regeneration of periodontium. Herein, we developed a novel method to manipulate the distribution and growth of periodontal ligament stem cells (PDLSCs) by utilizing highly paralleled static magnetic field (SMF) and magnetic nanoparticles (MNPs). PDLSCs were incubated with MNPs in vitro to label with them. Meanwhile, CCK8 and Live/dead cell staining assay were used to detect the impact of SMF and MNPs on cell viability. The directional migration and growth of PDLSCs were visualized under microscope. Furthermore, Real-time Quantitative PCR and western blot were utilized to calculate the expression level of periodontal ligament related genes. The results showed that PDLSCs could rapidly take up MNPs without compromising cell proliferation and viability, consequently endowed with the ability to respond via magnetic force. The cell migration analysis indicated that PDLSCs could move along the magnetic induction line, testifying that SMF exerted forces on PDLSCs that labeled with MNPs. It was demonstrated that collective application of SMF and MNPs not only induced PDLSCs organized and grew directionally, but also initiated elongation of cells and nucleus. Furthermore, the morphological alteration of the nucleus could also effectively enhance the gene and protein expression of Collagen Ⅰα2, Collagen Ⅲ and Periostin, suggesting the capability of PDLSCs to differentiate into PDL. In conclusion, this study exhibits a new approach for directional reconstruction of PDL to obtain physiological and functional regeneration of periodontium.
研究领域:
口腔科学
·
组织工程
·
干细胞生物学
·
磁生物技术
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产品关联
DOI
PubMed
高影响因子
Stem Cell Research & Therapy
·
2025
·Vol. 16
·期 1
·683
·
IF 7.3
Zhuang Jianjian,Li Yue,Huang Yi Ling,Wang Xiang,Lin Neng Ming
Background Mesenchymal stem cells (MSCs) undergo senescence after expansion and in vitro culture under oxidative stress, which limits their clinical application. Ginsenoside Rh2 has been confirmed to regulate mitochondrial function, but its role in modulating the senescence of MSCs has not been clearly investigated. Purpose This study aims to explore the effects and underlying mechanisms of Rh2 in inhibiting the senescence of MSCs. Methods Transmission electron microscopey (TEM) and fluorescence staining assays were used to monitor changes in mitochondrial and lysosomal morphology and function in Rh2-treated senescent MSCs. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analyses were performed to evaluate the expression levels of senescence-related cytokine genes and proteins. Results Rh2 can inhibited the senescence of MSCs by activating Sirtuin 1(SIRT1). At the molecular level, SIRT1 regulated the Pink1/Parkin-mediated mitophagy pathway and suppressed the secretion of senescence-associated cytokines (IL-6 and IL-8). Additionally, Rh2 influenced lysosomal stability and sultimately inhibited exosome secretion through direct activation of SIRT1. Conclusion These findings provide a potential strategy for using Rh2 to overcome the senescence of MSCs, thereby enhancing their clinical application. Graphical
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DOI
PubMed
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2020
·Vol. 138
·期 19
·50392
·
IF 2.52
Xing Cao,Xiangli Liu,Yan Liu,Rui Ma,Shichang Sun
Numerous cells grow in columnar tissues and organs with different curvatures and curvature gradients. Therefore, it is necessary to study the effect of curvature on cell behavior to control and promote cell development. Herein, we prepared polydimethylsiloxane (PDMS) with different micro-nano patterns using ultraviolet soft lithography. Hydrophilic polydopamine (PDA) was modified on the PDMS surface to prepare PDMS/PDA to improve its biocompatibility. The PDMS/PDA was characterized by contact angle tester and scanning electron microscopy (SEM). The effect of curvature on bone cell migration and differentiation was studied through SEM, inverted phase contrast microscope and fluorescence microscopy. We found that different curvatures had different effects on the bone cell migration and differentiation. Chondrocytes migrated rapidly in grooves with a curvature range of 1/575–1/875 μm −1 . Bone mesenchymal stem cells (BMSCs) had high efficiency of differentiation into chondrocytes in the grooves with a curvature range of 1/775–1/1375 μm −1 . Furthermore, BMSCs showed high efficiency of differentiation into chondrocytes at the edges of micro-nano patterns with different perimeter curvatures, and the differentiation efficiency was the highest at 120° convex curvature. This work shows that curvature is a principle to be considered in bone tissue regeneration engineering and provides inspiration for future biomaterials design.
研究领域:
生物医学工程
·
细胞生物学
·
组织工程
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DOI
高影响因子
CELL PROLIFERATION
·
2023
·
IF 8.5
Yun Lv,Ziyan Rao,Lulu Liu,Jun Jia,Chenyang Wu,Jun Xu,Yuanyuan Du,Yinan Liu,Bei Liu,Jihang Shi,Guangya Li,Dongyu Zhao,Hongkui Deng
Derivation of human hepatocytes from pluripotent stem cells in vitro has important applications including cell therapy and drug discovery. However, the differentiation of pluripotent stem cells into hepatocytes in vitro was not well recapitulated the development of liver. Here, we developed a differentiation protocol by mimicking the two-stage development of hepatoblasts, which permits the efficient generation of hepatic progenitor cells from chemically induced pluripotent stem cells (hCiPSCs). Single-cell RNA sequencing (scRNA-seq) indicates the similarity between hepatoblasts differentiated in vitro and in vivo. Moreover, hCiPSC-derived hepatic progenitor cells can further differentiate into hepatocytes that are similar to primary human hepatocytes with respect to gene expression and key hepatic functions. Our results demonstrate the feasibility of generating hepatic progenitor cells and hepatocytes from hCiPSCs with high efficiency and set the foundation for broad translational applications of hCiPSC-derived hepatocytes.
研究领域:
干细胞研究
·
分子生物学
·
再生医学
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2013
·
IF 3.479
Yi Deng,Xiaohong Zhang,Yinghui Zhao,Shangshang Liang,Anxiu Xu,Xiang Gao,Feng Deng,Jing Fang,Shicheng Wei
Realization of the full potential of human induced pluripotent stem cells (hiPSCs) in clinical applications requires development of well-defined conditions for their growth and differentiation. A novel fully defined polyvinyl alcohol/hyaluronan (PVA/HA) polysaccharide nanofiber was developed for hiPSCs culture in commercially available xeno-free, chemically defined medium. Vitronectin peptide (VP) was immobilized to PVA/HA nanofibers through NHS/EDC chemistry. The hiPSCs successfully grew and proliferated on the VP-decorated PVA/HA nanofibers, similar to those on Matrigel™. Such well-defined, xeno-free and safe nanofiber substrate that supports culture of hiPSCs will not only help to accelerate the translational perspectives of hiPSCs, but also provide a platform to investigate the cell–nanofiber interaction mechanisms that regulate stem cell proliferation and differentiation.
研究领域:
生物材料学
·
干细胞研究
·
再生医学
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DOI
PubMed
高影响因子
ZOOLOGICAL RESEARCH
·
2023
·
IF 4.9
Cong Li,Rui Bi,Lin Wang,Yu-Hua Ma,Yong-Gang Yao,Ping Zheng
Tree shrews ( Tupaia belangeri chinensis ) share a close relationship to primates and have been widely used in biomedical research. We previously established a spermatogonial stem cell (SSC)-based gene editing platform to generate transgenic tree shrews. However, the influences of long-term expansion on tree shrew SSC spermatogenesis potential remain unclear. Here, we examined the in vivo spermatogenesis potential of tree shrew SSCs cultured across different passages. We found that SSCs lost spermatogenesis ability after long-term expansion (>50 passages), as indicated by the failure to colonize the seminiferous epithelium and generate donor spermatogonia (SPG)-derived spermatocytes or spermatids marking spermatogenesis. RNA sequencing (RNA-seq) analysis of undifferentiated SPGs across different passages revealed significant gene expression changes after sub-culturing primary SPG lines for more than 40 passages on feeder layers. Specifically, DNA damage response and repair genes (e.g., MRE11 , SMC3 , BLM , and GEN1 ) were down-regulated, whereas genes associated with mitochondrial function (e.g., NDUFA9 , NDUFA8 , NDUFA13 , and NDUFB8 ) were up-regulated after expansion. The DNA damage accumulation and mitochondrial dysfunction were experimentally validated in high-passage cells. Supplementation with nicotinamide adenine dinucleotide (NAD + ) precursor nicotinamide riboside (NR) exhibited beneficial effects by reducing DNA damage accumulation and mitochondrial dysfunction in SPG elicited by long-term culture. Our research presents a comprehensive analysis of the genetic and physiological attributes critical for the sustained expansion of undifferentiated SSCs in tree shrews and proposes an effective strategy for extended in vitro maintenance.
研究领域:
生物医学研究
·
干细胞生物学
·
分子遗传学
·
生殖生物学
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DOI
PubMed
高影响因子
Regenerative Therapy
·
2022
·
IF 3.651
Ji-Hua Xu,Sheng-Quan Xu,Shi-Li Ding,Hu Yang,Xin Huang,Hai-Fei Shi
Introduction Although bone marrow-derived mesenchymal stem cells (BMSCs) have attracted increasing attention because of their pivotal functions in the process of wound healing and fibrosis alleviation, the underlying molecular mechanisms have been poorly understood. Moreover, transforming growth factor beta 1 (TGF-β1) is positively correlated with scar formation, whereas TGF-β3 inhibits the pathological scar formation process. However, the relation of TGF-β1, TGF-β3, and the TGF-β/Smad signaling pathway with BMSCs is unknown and requires further investigation. Methods A cell co-culture platform was used to examine the relationship between BMSCs and dermal fibroblasts (DFs). EdU labelling and cell cycle detection were carried out to examine the viability of DF cells. Transwell and wound healing assays were used to test the cell migration of DFs. The expression of TGF-β pathway components and collagens were determined by RT-qPCR and western blotting. A damaged skin rat model was applied to test the effects of BMSC treatment on skin wound healing. Results The results showed that BMSC secretion could inhibit the viability and migration of DFs. Moreover, we observed that the TGF-β-induced expression of TGF-β1, Smad2, Smad3, COLI and COLIII was attenuated upon BMSC treatment in DFs, while the decrease in TGF-β3 expression was enhanced by BMSCs. Furthermore, BMSC treatment accelerated wound healing and attenuated skin collagen deposition in a damaged skin rat model, leading to the mitigation of cell proliferation and enhancement of cell apoptosis. In addition, the expression of alpha-smooth muscle actin (α-SMA), COLI, and COLII was alleviated by BMSC treatment. Conclusions Our results indicate that BMSCs can promote wound healing and inhibit skin collagen deposition, which is associated with the TGF-β/Smad signaling pathway.
研究领域:
干细胞生物学
·
伤口愈合
·
纤维化
·
分子生物学
·
细胞信号传导
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 27
·5218-5230
·
IF 7.571
Rui Zhang,Ye He,Bailong Tao,Jing Wu,Xinqiang Hu,Xuan Li,Zengzilu Xia,Kaiyong Cai
A scaffold is one of the most significant implants for treating bone injury, while the precise control of stem cell proliferation and differentiation within a scaffold is still challenging. In this work, a composite scaffold was designed to be capable of recruiting endogenous stem cells, stimulating osteogenic differentiation and achieving significant bone repair function. The designed SiCP + SF@PFS silica–calcium phosphate composite scaffold was obtained by mixing the peptide PFS containing silk fibroin solution with the SiCP scaffold, and treating with horseradish peroxidase and H2O2. The results showed that the composite scaffold was able to release the PFS peptide continuously to induce the migration of mesenchymal stem cells. Meanwhile, cell proliferation and osteogenic differentiation were also improved after being seeded on the scaffold. In the cranial defect rat model, the composite scaffold was able to recruit CD29+ and CD90+ cells one week after implantation around the injury sites. The results of Micro-CT, H&E staining, Masson's staining and immunohistochemical staining indicated that the composite scaffold was able to promote new bone formation significantly.
研究领域:
生物材料
·
组织工程
·
再生医学
·
生物医学工程
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DOI
PubMed
高影响因子
Science of Advanced Materials
·
2022
·Vol. 14
·期 3
·603-611
·
IF 1.067
Tian Mei,Lian Yunfei,Gao Jing,Yu Fengxiang,Song Ge,Cao Jin,Li Juan,Ullah Aftab,Qi Xueyong
The delivery of therapeutic cancer agents via nanomaterials has received significant attention. However, because of the absence of tumour targeting, tumour treatment strategies are still not satisfactory. Umbilical cord mesenchymal stem cells are inherently prone to migrate to malignant
sites, enabling them to deliver antitumour drugs effectively. Therefore, it is expected to be a promising tool for tumour targeting. In this study, we constructed magnetic drug-loaded nanoparticles comprised of ferroferric oxide and doxorubicin, which were ingested by umbilical cord mesenchymal
stem cells and precisely delivered to the tumour sites. Here, we physicochemically characterized the nanoparticles for the particle size, biocompatibility and cellular uptake. The umbilical cord mesenchymal stem cells migration and homing ability before and after drug loading were evaluated.
The anti-cancer effect of stem cells loaded with nanoparticles was determined using MCF-7 cells. In vitro studies, the magnetic drug-loaded nanoparticles complex on tumour cells revealed that umbilical cord mesenchymal stem cells could transport magnetic drug-loaded nanoparticles to
induce robust apoptosis.
研究领域:
纳米技术
·
癌症治疗
·
干细胞研究
·
药物递送系统
·
生物医学工程
✓ 已验证
DOI
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Wu Shuo,Wang Zongliang,Wang Yu,Guo Min,Zhou Mengyang,Wang Liqiang,Ma Jie,Zhang Peibiao
Mesenchymal stem cells (MSCs) have considerable value in regenerative medicine because of their unique properties such as pluripotency, self-renewal ability, and low immunogenicity. Isolation and purification are prerequisites for various biomedical applications of MSCs, and traditional sorting methods are often expensive, complicated, and difficult to apply on a large scale. In addition to purification, the requirement for expansion of cells also limits the further application of MSCs. The purpose of this study was to develop a unique magnetic sorting microsphere to obtain relatively pure and high-yield MSCs in an economical and effective way, that can also be used for the expansion of MSCs. Poly (ethylene glycol) (PEG)-based anti-adhesive treatment of the prepared oleic acid grafted Fe3O4-poly (lactic-co-glycolic acid) magnetic microspheres was performed, and then E7 peptide was covalently grafted onto the treated microspheres. Upon a series of characterization, the magnetic microspheres were of uniform size, and cells were unable to adhere to the PEG-treated surface. E7 grafting significantly improved cell adhesion and proliferation. The results obtained from separate culture of various cell types as well as static or dynamic co-culture showed that selective adhesion of MSCs was observed on the magnetic sorting microspheres. Furthermore, the cells expanded on the microspheres maintained their phenotype and typical differentiation potentials. The magnetic properties of the microspheres enabled sampling, distribution, and transfer of cells without the usage of trypsin digestion. And it facilitated the separation of cells and microspheres for harvesting of MSCs after digestion. These findings have promising prospects for MSC research and clinical applications.
研究领域:
再生医学
·
干细胞生物学
·
生物医学工程
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DOI
PubMed
高影响因子
Stem Cell Research
·
2016
·
IF 3.892
Min Jin,Yutao Wu,Yanwei Wang,Danqing Yu,Mei Yang,Feng Yang,Chun Feng,Ting Chen
MicroRNA-29a (miR-29a) has been extensively studied in tumor biology and fibrotic diseases, but little is known about its functional roles in vascular smooth muscle cell (VSMC) differentiation from embryonic stem cells (ESCs). Using well-established VSMC differentiation models, we have observed that miR-29a induces VSMC differentiation from mouse ESCs by negatively regulating YY1, a transcription factor that inhibits muscle cell differentiation and muscle-specific gene expression. Moreover, gene expression levels of three VSMC specific transcriptional factors were up-regulated by miR-29a over-expression, but down-regulated by miR-29a inhibition or YY1 over-expression. Taken together, our data demonstrate that miR-29a and its target gene, YY1, play a regulatory role in VSMC differentiation from ESCs in vitro and in vivo .
研究领域:
分子生物学
·
干细胞研究
·
心血管生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）