Tissue Engineering and Regenerative Medicine
·
2023
·
IF 3.6
Ye Yuanjian,Zhong Haobo,Huang Shoubin,Lai Weiqiang,Huang Yizhi,Sun Chunhan,Zhang Yanling,Zheng Shaowei
Background: Implantation of bone marrow mesenchymal stem cells (BMSCs) is a potential alternative for promoting bone defects healing or osseointegration in osteoporosis. However, the reactive oxygen species (ROS) accumulated and excessive inflammation in the osteoporotic microenvironment could weaken the self-replication and multi-directional differentiation of transplanted BMSCs. Methods: In this study, to improve the hostile microenvironment in osteoporosis, Poloxamer 407 and hyaluronic acid (HA) was crosslinked to synthetize a thermos-responsive and injectable hydrogel to load MnO 2 nanoparticles as a protective carrier (MnO 2 @Pol/HA hydrogel) for delivering BMSCs. Results: The resulting MnO 2 @Pol/HA hydrogel processed excellent biocompatibility and durable retention time, and can eliminate accumulated ROS effectively, thereby protecting BMSCs from ROS-mediated inhibition of cell viability, including survival, proliferation, and osteogenic differentiation. In osteoporotic bone defects, implanting of this BMSCs incorporated MnO 2 @Pol/HA hydrogel significantly eliminated ROS level in bone marrow and bone tissue, induced macrophages polarization from M1 to M2 phenotype, decreased the expression of pro-inflammatory cytokines (e.g . , TNF-α, IL-1β, and IL-6) and osteogenic related factors (e.g., TGF-β and PDGF). Conclusion: This hydrogel-based BMSCs protected delivery strategy indicated better bone repair effect than BMSCs delivering or MnO 2 @Pol/HA hydrogel implantation singly, which providing a potential alternative strategy for enhancing osteoporotic bone defects healing.
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高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Jiahui Zhang,Wei Xin,Yechi Qin,Yuhao Hong,Zijie Xiahou,Kunxi Zhang,Peiliang Fu,Jingbo Yin
Based on “bottom-up” strategy, cell-laden 3D bioprinting is an important process of fabricating sophisticated biomimetic structures. Stem cell spheroids possess better biological properties and are advanced as printing units. However, efficient and convenient preparation, collection and printing of cell spheroids remains a challenge. The present study developed a composite granular hydrogel acted as “all-in-one” multi-functional bioink to realize Adipose-derived stem cell (ASC) spheroids Production and reorganization. Poly(sulfobetaine methacrylate) (PSBMA) based microspheres were fabricated and self-assembled to a granular hydrogel. Then, N -isopropylacrylamide (NIPAM) and SBMA were co-polymerized in-situ inside of assembled PSBMA microspheres to further crosslink the assembled microspheres, forming a composite granular hydrogel, which possesses bulk feature and shear-thinning, self-healing properties. Caves were created by compressing composite granular hydrogels into sugar particles that removed via dissolution in water. Due to the non-fouling feature and the porous structure, numerous ASC spheroids were formed spontaneously inside the porous composite granular hydrogel, which were transferred conveniently to 3D printer. The spheroids-laden composite granular hydrogels showed well-performed extrudability and fidelity, realizing reorganization of the produced spheroids to the stable 3D constructs for further in vitro culture . ASC spheroids in granular hydrogel after 3D printing showed high level of viability and stemness, as well as efficient chondrogenic/osteogenic/adipogenic differentiation. The composite granular hydrogel thus shows potential toward stem cell researches such as organoids construction. The results of both in vitro drug toxicity and in vivo cartilage regeneration experiments showed spheroids-laden granular hydrogel is promising in drug screening and tissue regeneration.
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2020
·Vol. 109
·期 7
·1209-1219
·
IF 3.525
Yinping Tian,Minyi Liu,Yaoyao Liu,Changzheng Shi,Yayu Wang,Tong Liu,Yi Huang,Peihua Zhong,Jian Dai,Xiangning Liu
Bone tissue plays an important role in supporting and protecting the structure and function of the human body. Bone defects are a common source of injury and there are many reconstruction challenges in clinical practice. However, 3D bioprinting of scaffolds provides a promising solution. Hydrogels have emerged as biomaterials with good biocompatibility and are now widely used as cell-loaded materials for bioprinting. This study involved three steps: First, sodium alginate (SA), gelatin (Gel), and nano-hydroxyapatite (na-HA) were mixed into a hydrogel and its rheological properties assessed to identify the optimum slurry for printing. Second, SA/Gel/na-HA bioscaffolds were printed using 3D bioprinting technology and their physical properties characterized for surface morphology, swelling, and mechanical properties. Finally, human periodontal ligament stem cells (hPDLSCs) were mixed with SA/Gel/na-HA printing slurry to create a “bioink” to prepare SA/Gel/na-HA/ hPDLSCs cell bioscaffolds. These were tested for biocompatibility and osteogenic differentiation performance using live/dead cell staining, cell adhesion, cell proliferation, and alkaline phosphatase activity. The SA/Gel/na-HA hydrogel exhibited shear-thinning behavior. The equilibrium swelling of the bioscaffold was 125.9%, the compression stress was 0.671 MPa, and the compression elastic modulus was 8.27 MPa. The SA/Gel/na-HA/hPDLSCs cell bioscaffolds caused effective stimulation of cell survival, proliferation, and osteoblast differentiation. Therefore, the SA/Gel/na-HA/hPDLSCs cell bioscaffolds displayed potential as a material for bone defect reconstruction.
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Biomaterials Science
·
2020
·Vol. 8
·期 11
·3095-3105
·
IF 6.183
Yuyang Xia,Hongying Bao,Jie Huang,Xiaodi Li,Chenggong Yu,Zhijun Zhang,Haishui Wang
Human mesenchymal stem cells (hMSCs) are promising in the treatment of pulmonary fibrosis (PF). However, the behavior of hMSCs after transplantation, including dynamic translocation, location and survival, impeding the clinical application of hMSCs in PF is still ambiguous. Herein, we report an effective dual-labeling strategy combining endogenous bioluminescence imaging (BLI) and exogenous near-infrared-persistent luminescence (NIR-PL) imaging for in situ visualization of the transplanted stem cells. The long persistent luminescence nanoparticles (LPLNPs), Zn1.1Ga1.8Ge0.1O4:Cr3+,Eu3+, were developed to track the dynamic translocation, position and distribution of the transplanted hMSCs, taking advantage of their long-lasting NIR-PL imaging ability and minimal autofluorescence background interference. Moreover, in virtue of their ability to express red-emitting firefly luciferase (RfLuc), the living stem cells after transplantation could be discriminated from the dead cells by BLI. This facile pattern contributes to the in situ monitoring of stem cells regarding their spontaneous behavior in vivo and therefore deepening our knowledge in the role played by the transplanted hMSCs in PF therapy.
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JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
·
2020
·
IF 6.155
Jing Li,Zhenqiang Feng,Ning Gu,Fang Yang
Micro/nanobubbles for use as ultrasound contrast agents have been fabricated with different shell materials. When various biomedical nanoparticles have been embedded in the shells of bubbles, the composite structures have shown promising applications in multi-modal imaging, drug/gene delivery, and biomedical sensing. In this study, we developed a new gas-liquid interface self-assembly method to prepare magnetic nanobubbles embedded with superparamagnetic iron oxide nanoparticles (SPIONs). The diameter of the generated assembled nanobubbles was 227.40 ± 87.21 nm with a good polydispersity index (PDI) of 0.29. Under the condition of 150 compression cycles, the nanobubble concentration could reach about 6.12 × 10 9 /mL. Transmission electron microscopy (TEM) and scanning electronic microscopy (SEM) demonstrated that the assembled nanobubbles had a hollow gas core with SPIONs adsorbed on the surface. Ultrasound (US) imaging and magnetic resonance imaging (MRI) experiments indicated that the assembled magnetic nanobubbles exhibited good US and MR contrast capabilities. Moreover, the assembled magnetic nanobubbles were used to label neural stem cells under ultrasound exposure. After 40 s US exposure, the magnetic nanobubbles could be delivered into cells with 2.80 pg Fe per cell, which could be observed in the intracellular endosome by TEM. Compared with common incubation methods, the ultrasound exposure method did not introduce the potential cytotoxicity of transfection reagents and the efficiency was about twice as high as the efficiency of incubation. Therefore, the assembled magnetic nanobubbles prepared through the pressure-driven gas-liquid interface assembly approach could be a potential US/MRI dual model imaging nanocarrier for regenerative applications.
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Nanoscale Research Letters
·
2021
·Vol. 16
·期 1
·1-13
·
IF 4.703
An Li,Tao Qing,Wu Yue,Wang Nana,Liu Yan,Wang Feifei,Zhang Lixing,Shi Aihua,Zhou Xiumin,Yu Shuang,Zhang Jingzhong
Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the midbrain, and the stem cell transplantation method provides a promising strategy for the treatment. In these studies, tracking the biological behaviors of the transplanted cells in vivo is essential for a basic understanding of stem cell function and evaluation of clinical effectiveness. In the present study, we developed a novel ultrasmall superparamagnetic iron oxide nanoparticles coating with the polyacrylic acid (PAA) and methoxypolyethylene glycol amine (PEG) by thermal decomposition method and a two-step modification. The USPIO-PAA/PEG NPs have a uniform diameter of 10.07 ± 0.55 nm and proper absorption peak of the corresponding ligands, as showed by TEM and FTIR. MTT showed that the survival of cells incubated with USPIO-PAA/PEG NPs remained above 96%. The synthesized USPIO-PAA/PEG had a good relaxation rate of 84.65 s −1 Mm −1 , indicating that they could be efficiently uptake and traced by MRI. Furthermore, the primary human adipose-derived stem cells (HADSCs) were characterized, labeled with USPIO-PAA/PEG and transplanted into the striatum of 6-hydroxydopamine (6-OHDA)-induced PD rat models. The labeled cells could be traced by MRI for up to 3 weeks after the transplantation surgery; moreover, transplantation with the labeled HADSCs significantly attenuated apomorphine-induced rotations in PD models and increased the number of the dopaminergic neurons in the substania nigra . Overall, the development of USPIO-PAA/PEG NPs provides a promising tool for in vivo tracing technique of cell therapy and identifies a novel strategy to track stem cells with therapeutic potential in PD.
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ACS Biomaterials Science & Engineering
·
2021
·
IF 4.749
Chuanchuan Lin,Ye He,Kun Xu,Qian Feng,Xuan Li,Songyue Zhang,Ke Li,Ruqing Bai,Hong Jiang,Kaiyong Cai
The mechanical properties of the natural extracellular matrix (ECM) change extensively, but these specific properties provide a relatively stable environment for resident cells. Although the effect of matrix stiffness on cell functions has been widely studied, the molecular mechanism was still not fully understood. Matrix stiffening is a common phenomenon in tissue damaging processes. To explore the effect of the increase in local matrix stiffness on cell behaviors, a three-dimensional (3D) cell culture system with a tunable modulus but constant other physical parameters was constructed by the alginate hydrogel with different molecular weights and cross-linking degrees. By using this culture system, the transcriptome response of mesenchymal stem cells (MSCs) to matrix stiffness was explored. Furthermore, a finite element model was developed to simulate the interaction between cells and the matrix. Results revealed that the increased matrix stiffness promoted the proliferation-related signaling of MSCs, and this process depended on the increased cortex tension caused by the activation of RAS and myosin II.
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PLoS Genetics
·
2021
·Vol. 17
·期 7
·e1009649
·
IF 5.917
Kun Wu,Yiming Tang,Qiaoqiao Zhang,Zhangpeng Zhuo,Xiao Sheng,Jingping Huang,Jie’er Ye,Xiaorong Li,Zhiming Liu,Haiyang Chen
The differentiation efficiency of adult stem cells undergoes a significant decline in aged animals, which is closely related to the decline in organ function and age-associated diseases. However, the underlying mechanisms that ultimately lead to this observed decline of the differentiation efficiency of stem cells remain largely unclear. This study investigated Drosophila midguts and identified an obvious upregulation of caudal ( cad ), which encodes a homeobox transcription factor. This factor is traditionally known as a central regulator of embryonic anterior-posterior body axis patterning. This study reports that depletion of cad in intestinal stem/progenitor cells promotes quiescent intestinal stem cells (ISCs) to become activate and produce enterocytes in the midgut under normal gut homeostasis conditions. However, overexpression of cad results in the failure of ISC differentiation and intestinal epithelial regeneration after injury. Moreover, this study suggests that cad prevents intestinal stem/progenitor cell differentiation by modulating the Janus kinase/signal transducers and activators of the transcription pathway and Sox21a-GATAe signaling cascade. Importantly, the reduction of cad expression in intestinal stem/progenitor cells restrained age-associated gut hyperplasia in Drosophila . This study identified a function of the homeobox gene cad in the modulation of adult stem cell differentiation and suggested a potential gene target for the treatment of age-related diseases induced by age-related stem cell dysfunction.
Adult stem cells undergo an aging-related decline of differentiation efficiency in aged animals. However, the underlying mechanisms that ultimately lead to this observed decline of differentiation efficiency in stem cells still remain largely unclear. By using the Drosophila midgut as a model system, this study identified the homeobox family transcription factor gene caudal ( cad ), the expression of which is significantly upregulated in intestinal stem cells (ISCs) and progenitor cells of aged Drosophila . Depletion of cad promoted quiescent ISCs to become activate and produce enterocytes (ECs) in midguts under normal gut homeostasis conditions; However, overexpression of cad resulted in the failure of ISC differentiation and intestinal epithelial regeneration after injury. Moreover, cad prevents ISC-to-EC differentiation by inhibiting JAK/STAT signaling, and the expressions of Sox21a and GATAe . Reduction of cad expression in intestinal stem/progenitor cells restrained age-associated gut hyperplasia in Drosophila . These findings enable a detailed understanding of the roles of homeobox genes in the modulation of adult stem cell aging in humans. This will be beneficial for the treatment of age-associated diseases that are caused by a functional decline of stem cells.
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高影响因子
PHYTOTHERAPY RESEARCH
·
2019
·Vol. 34
·期 4
·817-824
·
IF 3.766
Mingming Zhu,Xi Yu,Zongmei Zheng,Jiaming Huang,Xuepan Yang,Hongfei Shi
Cancer stem cells (CSCs) are considered as the origin and driving cells of cancer, and play a key role in the progress of cancer. Studies have shown that capsaicin exerted inhibitory effect on prostate cancer cells, however, the effects of capsaicin on prostate CSCs remain undefined. In the present study, we showed that capsaicin could downregulate prostate CSCs markers and inhibit the growth of PC-3 and DU145 prostate cancer stem cells. Further, we found capsaicin suppressed the expression of Wnt-2, p-GSK3β and β-catenin, along with downregulation of Wnt/β-catenin pathway target genes c-myc and cyclinD1. Using LiCl, a activator of Wnt/β-catenin pathway, we found activation of Wnt/β-catenin pathway could ameliorate the downregulation of prostate CSCs markers and the growth inhibition induced by capsaicin in prostate cancer stem cells. Those data suggested that the inhibition effect of capsaicin on prostate cancer stem cells and the anti-cancer effect of capsaicin on prostate cancer stem cell may be mediated by Wnt/β-catenin pathway. Findings from this study reveals for the first time the potential role and mechanisms of capsaicin on prostate cancer stem cells.
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高影响因子
MICROCHIMICA ACTA
·
2019
·Vol. 186
·期 2
·1-7
·
IF 5.479
Wang Yulong,Wang Limin,Zhang Cunzheng,Liu Fengquan
A DNAzyme-based catalytic and stem-loop based amplification scheme is used in a Cu(II)-specific lateral flow assay (LFA). Three test lines with given cut-off value on the test strip are set as the signal indicating zone for semiquantitative analysis by the number of red color bands that appear after lateral flow. The colored bands are generated by accumulation of gold nanoparticles. Four detection ranges can be visualied: (a) 0–2 ng·mL −1 (= negative); 2–50 ng·mL −1 ; 50–200 ng·mL −1 and > 200 ng·mL −1 of Cu(II) (= positive). The visual detection limit is thus considered as being 2 ng·mL −1 which is much lower than the U.S. EPA limit in drinking water (1.25 μg·mL −1 ). The highly specific DNAzyme, the strong multiple-turnover catalytic target recycling property and highly efficient amplification strategy warrant the high specificity, sensitivity and rapidity of this LFA. Conceivbly, this detecton scheme can be extended to other metal ions by proper choice of the ion-specific DNAzyme.
Schematic presentation of a semiquantitative lateral flow test strip for Cu 2+ analysis by three visual cut-off value test lines using catalytic and stem-loop based signal amplification strategy.
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INTERNATIONAL ENDODONTIC JOURNAL
·
2019
·Vol. 53
·期 1
·72-83
·
IF 3.331
T. Ning,J. Shao,X. Zhang,X. Luo,X. Huang,H. Wu,S. Xu,B. Wu,D. Ma
Aim To comparatively evaluate changes in the proliferation and mineralization abilities of dental pulp stem cells (DPSCs) from juvenile and adult rats in a lipopolysaccharide (LPS)-induced inflammatory microenvironment to provide a theoretical basis for the age-related differences observed in DPSCs during repair of inflammatory injuries. Methodology DPSCs were isolated from juvenile (JDPSCs) and adult rats (ADPSCs), and senescence-associated β-galactosidase staining was used to compare senescence between JDPSCs and ADPSCs. Effects of LPS on JDPSCs and ADPSCs proliferation were investigated by cell counting kit-8 assays and flow cytometry. Alizarin red staining, quantitative reverse transcription polymerase chain reaction and Western blot assay were used to examine the effects of LPS on mineralization-related genes and proteins in JDPSCs and ADPSCs. Immunohistochemistry was used to compare interleukin-1β (IL-1β) and osteocalcin (OCN) expression in the pulpitis model. Unpaired Student's t -tests and one-way anova were used for statistical analysis. Results DPSCs were isolated from juvenile and adult rat dental pulp tissues. At low concentrations (0.1–1 μg mL −1 ), LPS significantly promoted the proliferation of JDPSCs ( P < 0.01) and ADPSCs ( P < 0.01 or P < 0.05), with the effect being stronger in JDPSCs than in ADPSCs. In addition, mineralized nodules and the expression of mineralization-related genes ( OCN , DSPP , ALP , BSP ) increased significantly after stimulation with LPS (0.5 μg mL −1 ) in JDPSCs and ADPSCs ( P < 0.01 or P < 0.05), and JDPSCs displayed a more obvious increase than ADPSCs. Western blots revealed OCN and ALP expression levels in JDPSCs treated with LPS were significantly upregulated ( P < 0.05); meanwhile, ALP expression in ADPSCs increased slightly but significantly ( P < 0.05), and OCN expression was not affected. Finally, IL-1β expression was significantly higher ( P < 0.05) and OCN expression was significantly lower ( P < 0.05) in the inflamed dental pulp of adult rats than in juvenile rats. Conclusions A certain degree of inflammatory stimulation promoted the proliferation and mineralization of DPSCs; however, this effect declined with age. The DPSCs of adult donors in an inflammatory microenvironment have a weaker repair ability than that of juvenile donors, who are better candidates for tissues damage repair.
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Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 16
·2657-2666
·
IF 5.047
Maowen Chen,Yan Hu,Yanhua Hou,Menghuan Li,Maohua Chen,Caiyun Mu,Bailong Tao,Wei Zhu,Zhong Luo,Kaiyong Cai
Autophagy is associated with the proliferation and differentiation of mesenchymal stem cells (MSCs). In this study, we investigated the biological impact of silica-based nanobiomateiral-induced autophagy on the differentiation of MSCs, in which the nanoparticulate cues include solid silica nanoparticles (SSN), mesoporous silica nanoparticles (MSN) and biodegradable mesoporous silica nanoparticles (DMSN). The treatment with SSN significantly up-regulated the LC3-II expression via ERK1/2 and AKT/mTOR signaling pathways compared to DMSN and MSN, leading to a higher autophagic activity in MSCs. The enhanced protein adsorption of DMSN and MSN could prevent the direct interaction between cells and nanoparticles, which consequently reduces the autophagic stimulation of MSCs. It should be noted that MSCs exhibited increased differentiation potential when the autophagic activity was enhanced by the treatment with different nanoparticles. In comparison, no difference in the cell differentiation potential was found when an autophagy inhibitor (chloroquine, CQ) was incorporated in all groups. The study may contribute to the development of silica-based nanobiomaterials in the future.
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