Regenerative Medicine
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2022
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IF 3.21
Ming-Zhi Huang,Hong-Yan Chen,Guo-Xuan Peng,Hong Sun,Hong-Cheng Peng,Hai-Yang Li,Xiang-Hui Liu,Qing Li
Aim: Effect of artesunate (ART)-treated bone marrow-derived mesenchymal stem cells-derived exosomes (BMSC-Exos) on osteogenesis and its underlying mechanisms were investigated. Materials & methods: Proliferation, alkaline phosphatase activity and calcified nodule formation of osteoblasts were determined. A mouse model of osteoporosis was established by ovariectomy. Results:SNHG7 was upregulated in BMSC-Exos by twofold, which was further enhanced in ART-BMSC-Exos by about twofold. ART intensified BMSC-Exos-induced proliferation, alkaline phosphatase activity by about fourfold, calcified nodule formation by about threefold and upregulation of osteogenesis related molecules RUNX2 (by 50%), BMP2 (by 30%) and ATF4 (by 40%) via delivering SNHG7. Mechanistically, SNHG7 recruited TAF15 to facilitate RUNX2 stability. Conclusion: ART-BMSC-Exos facilitated osteogenesis via delivering SNHG7 by modulating TAF15/RUNX2 axis.Plain language summaryOsteoporosis is the most common and complex skeletal disorder worldwide. Exosomes derived from bone marrow-derived mesenchymal stem cells (BMSC-Exos) have been recognized as an ideal seed source for bone tissue regeneration. We aimed to explore the effect of artesunate (ART)-BMSC-Exos on osteogenesis and its underlying mechanisms. The results showed that ART-BMSC derived exosomal SNHG7 facilitated osteoblast activity and attenuated osteogenesis in mice by modulating TAF15/RUNX2 pathway. Our findings contribute to a better understanding of the therapeutic mechanisms of ART-BMSCs-Exos for osteoporosis and suggest ART-BMSC-Exos as a novel therapeutic option for osteoporosis.
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Biomaterials Advances
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2022
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IF 0
Yufeng Wang,Chen Ling,Jialin Chen,Haoyang Liu,Qingyun Mo,Wei Zhang,Qingqiang Yao
The fabrication of osteochondral scaffolds with both structural and biochemical cues to regulate endogenous bone marrow-derived mesenchymal stem cells (BMSCs) behavior for cartilage and subchondral bone regeneration is still a challenge. To this end, a composite scaffold (BE-PSA) with gradient structure and programmed biomolecule delivery was prepared by fused deposition modeling (FDM) 3D printing and multi-material-based modification. The 3D-printed polycaprolactone (PCL) scaffold included upper pores of 200 μm for cartilage regeneration and lower pores of 400 μm for bone regeneration. For a sequential modulation of BMSCs behavior, fast-degrading sodium alginate (SA) hydrogel was used to deliver a burst release of E7 peptide to enhance BMSCs migration within 72 h, while a slowly-degrading silk fibroin (SF) porous matrix was used to provide a sustained release of B2A peptide to improve BMSCs dual-lineage differentiation lasting for >300 h, depending on the different degradation rates of SA hydrogel and SF matrix. The BE-PSA scaffold had good biocompatibility and could improve the migration and osteogenic/chondrogenic differentiation of BMSCs. Benefiting from the synergistic effects of spatial structures and programmed biomolecule delivery, the BE-PSA scaffold showed enhanced cartilage and subchondral bone regeneration in rabbit osteochondral defect model. This work not only provides a promising scaffold to guide BMSCs behavior for osteochondral regeneration but also offers a method for the fabrication of tissue engineering biomaterials based on the structural and biochemical modification.
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Nano Energy
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2022
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IF 19.069
Guangbo Xia,Guobao Wang,Huiyi Yang,Wenbo Wang,Jian Fang
Cell-traction driven electrical stimulation on piezoelectric nanofibers mediates cell behavior without chemical factors or external stimuli, indicating a promising therapy at cell level. Generally, surface modification is required to achieve favorable cell adhesion for efficient electromechanical signal transmission. Nevertheless, common modification methodologies either easily fade away or destroy the nanostructure of piezoelectric nanofibers. Herein, with the assistance of ultrasound activated surface charges, in situ hydrophilic modification on piezoelectric poly( L -lactic acid) nanofibers is first proposed for cell adhesion. Due to the electrostatic interaction between dopamine and activated piezoelectric nanofiber, the efficient and robust in situ modification is obtained without compromising the nanofibrous structure. Stimulated by the piezoelectric nanofibers with modification, neural stem cells differentiate significantly into nerve cells on day 7 without exogenous growth factors . To our knowledge, the effect of inducing stem cell differentiation far outperforms that in previous reports. In addition, it has been demonstrated that the level of both cell differentiation and directional expansion is consistent with that of cell adhesion condition regardless of the intensity of electrical cue. This connection of cell adhesion and electro-topographical stimulation effects may guide the efforts in the design of electroactive scaffolds.
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ACS Biomaterials Science & Engineering
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2022
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IF 5.395
Zhangning Fu,Yanji Chu,Xiaodong Geng,Yingchao Ma,Kun Chi,Chengcheng Song,Shenglong Liao,Quan Hong,Di Wu,Yapei Wang
Acute kidney injury (AKI) has emerged as a major public health problem affecting millions of people worldwide without specific and satisfactory therapies due to the lack of an effective delivery approach. In the past few decades, hydrogels present infinite potential in localized drug delivery, while their poor adhesion to moist tissue and isotropic diffusion character always restrict the therapeutic efficiency and may lead to unwanted side effects. Herein, we proposed a novel therapeutic strategy for AKI via a customizable artificial kidney capsule (AKC) together with a mesenchymal stem cell (MSC)-laden hydrogel. Specifically, an elastic capsule owning an inner chamber with the same size and shape as the kidney is designed and fabricated through three-dimensional (3D) modeling and printing, serving as an outer wrap for kidney and cell-laden hydrogels. According to the in vitro experiment, the excellent biocompatibility of gelatin-based hydrogel ensures viability and proliferation of MSCs. In vivo mice experiments proved that this concept of AKC-assisted kidney drug delivery could efficiently reduce epithelial cell apoptosis and minimize the damage of the renal tubular structure for mice suffering AKI. Such a strategy not only provides a promising alternative in the treatment of AKI but also offers a feasible and versatile approach for the repair and recovery of other organs.
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高影响因子
CELLULOSE
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2023
·Vol. 30
·期 9
·5607-5622
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IF 5.7
Zhang Kecan,Li Jing,He Liang,Zhou Huajing,Guan Qingqing,Chen Keli,Shan Shaoyun,Hu Tianding
Cellulose nano/microfibres (CNFs/CMFs) with high aspect ratio were essential for mechanical strength and flexibility properties. In this study, the tobacco stem was employed as raw material for delignification with soda-oxygen (SO). By comparison with the caustic soda-anthraquinone (SAQ) treatment, based on process performance including pulp yield, residual lignin and fibre characteristics, the two-stage delignification process with total alkali 15% was selected for further preparing CNFs/CMFs with ultrasonication. Results showed that the aspect ratio of highly homogeneous CNFs/CMFs could achieve as ultra-high as 17,645. FTIR and XRD results showed that hemicellulose and lignin in CNFs/CMFs were widely removed, and the crystallinity was about 62%. TGA results exhibited that the degradation temperature was significantly enhanced to 330.2 °C. Finally, the CNF/CMF-based film was prepared and its folding endurance, tensile breaking strength, and burst strength could achieve 136, 61.28 N m/g, 278 kPa m 2 /g. The production of CNFs/CMFs from underutilized tobacco stems provided the potential to add value for industrial waste.
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Current Medical Science
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2023
·Vol. 43
·期 2
·223-231
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IF 2.4
Zhang Qing,Pan Rong-rong,Wu Yu-tao,Wei Yu-miao
Objective Vascular smooth muscle cell (VSMC) differentiation from stem cells is one source of the increasing number of VSMCs that are involved in vascular remodeling-related diseases such as hypertension, atherosclerosis, and restenosis. MicroRNA-146a (miR-146a) has been proven to be involved in cell proliferation, migration, and tumor metabolism. However, little is known about the functional role of miR-146a in VSMC differentiation from embryonic stem cells (ESCs). This study aimed to determine the role of miR-146a in VSMC differentiation from ESCs. Methods Mouse ESCs were differentiated into VSMCs, and the cell extracts were analyzed by Western blotting and RT-qPCR. In addition, luciferase reporter assays using ESCs transfected with miR-146a/mimic and plasmids were performed. Finally, C57BL/6J female mice were injected with mimic or miR-146a-overexpressing ESCs, and immunohistochemistry, Western blotting, and RT-qPCR assays were carried out on tissue samples from these mice. Results miR-146a was significantly upregulated during VSMC differentiation, accompanied with the VSMC-specific marker genes smooth muscle-alpha-actin (SMαA), smooth muscle 22 (SM22), smooth muscle myosin heavy chain (SMMHC), and h1-calponin. Furthermore, overexpression of miR-146a enhanced the differentiation process in vitro and in vivo . Concurrently, the expression of Kruppel-like factor 4 (KLF4), predicted as one of the top targets of miR-146a, was sharply decreased in miR-146a-overexpressing ESCs. Importantly, inhibiting KLF4 expression enhanced the VSMC-specific gene expression induced by miR-146a overexpression in differentiating ESCs. In addition, miR-146a upregulated the mRNA expression levels and transcriptional activity of VSMC differentiation-related transcription factors, including serum response factor (SRF) and myocyte enhancer factor 2c (MEF-2c). Conclusion Our data support that miR-146a promotes ESC-VSMC differentiation through regulating KLF4 and modulating the transcription factor activity of VSMCs.
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BIOMATERIALS
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2021
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IF 12.479
Chuanchuan Lin,Ye He,Qian Feng,Kun Xu,Zhe Chen,Bailong Tao,Xuemin Li,Zengzilu Xia,Hong Jiang,Kaiyong Cai
To control the fate of mesenchymal stem cells (MSCs) in a 3D environment by adjusting the mechanical parameters of MSC-loading scaffolds, is one of the hot topics in the field of regenerative biomaterials. However, a thorough understanding of the relevant MSCs behaviors affected by viscoelasticity , a dynamic physical parameter of scaffolds, is still lacking. Herein, we established an alginate hydrogel system with constant stiffness and tunable stress relaxation rate, which is a key parameter for the viscoelastic property of material. MSCs were cultured inside three groups of alginate hydrogels with various stress relaxation rates, and then RNA-seq analysis of cells was performed. Results showed that the change of stress relaxation rates of hydrogels regulated the most of the different expression genes of MSCs, which were enriched in cell proliferation-related pathways. MSCs cultured in hydrogels with fast stress relaxation rate presented a high self-renewal proliferation profile via activating phosphatidylinositol 3- kinase (PI3K)/protein kinase B (Akt) pathway. In contrast, a slow stress relaxation rate of hydrogels induced MSCs to enter a reversible quiescence state due to the weakened PI3K/Akt activation. Combined with a further finite element analysis , we speculated that the quiescence of MSCs could be served as a positive strategy for MSCs to deal with the matrix with a low deformation to keep stemness. Based on the results, we identified that stress relaxation rate of hydrogel was a potential physical factor of hydrogel to regulate the self-renewal or quiescence of MSCs. Thus, our findings provide a significant guiding principle for the design of MSCs-encapsulated biomaterials.
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INTERNATIONAL IMMUNOPHARMACOLOGY
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2023
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IF 5.6
Yao Guo,Jing Cui,Xueyi Liang,Taoyu Chen,Chong Lu,Tao Peng
Pancreatic cancer (PC) is a serious threat to human health, with most patients diagnosed at the advanced stages of the disease. Treatment with gemcitabine (GEM) leads to PC GEM resistance. In addition, cancer stem cell (CSC)-derived exosomes play an important role in cancer progression. We aimed to investigate the role and mechanism of action of PC stem cell-derived exosomes in PC drug resistance and progression. CSC-derived exosomes increased the proportion of F4/80+/CD86 + cells and levels of M2 polarization factors. miR-210 is expressed in CSC-derived exosomes. Thus, following co-culture, miR-210 was taken up by macrophages. Transfection or the addition of miR-210 mimics increased the proportion of F4/80+/CD206 + cells and levels of M2 polarization factors. Further, the miR-210 targets inhibited the levels of FGFRL1. The FGFRL1 overexpression plasmid also inhibited miR-210-mediated M2 polarization. After co-culture of THP-M2 cells with PC cells and treatment with GEM, the survival rate, migration rate, and levels of MDR, YB-1, BCRP, p-PI3K, p-AKT, and p-mTOR in PC cells increased. And THP-M2 increased the tumor volume and MDR, YB-1, BCRP, p-PI3K, p-AKT, and p-mTOR levels. Overall, miR-210 from PC stem cell-derived exosome targets and inhibits FGFRL1 to promote macrophage M2 polarization, which activates the p-PI3K/p-AKT/p-mTOR pathway and increases GEM resistance.
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International Journal of Nanomedicine
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2023
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IF 8
Yucheng Lin,Lu Zhang,Nancy Q Liu,Qingqiang Yao,Ben Van Handel,Yan Xu,Chen Wang,Denis Evseenko,Liming Wang
Purpose In order to accelerate the tendon-bone healing processes and achieve the efficient osteointegration between the tendon graft and bone tunnel, we aim to design bioactive electrospun nanofiber membranes combined with tendon stem/progenitor cells (TSPCs) to promote osteogenic regeneration of the tendon and bone interface.Methods In this study, nanofiber membranes of polycaprolactone (PCL), PCL/collagen I (COL-1) hybrid nanofiber membranes, poly(dopamine) (PDA)-coated PCL nanofiber membranes and PDA-coated PCL/COL-1 hybrid nanofiber membranes were successfully fabricated by electrospinning. The biochemical characteristics and nanofibrous morphology of the membranes, as well as the characterization of rat TSPCs, were defined in vitro. After co-culture with different types of electrospun nanofiber membranes in vitro, cell proliferation, viability, adhesion and osteogenic differentiation of TSPCs were evaluated at different time points.Results Among all the membranes, the performance of the PCL/COL-1 (volume ratio: 2:1 v/v) group was superior in terms of its ability to support the adhesion, proliferation, and osteogenic differentiation of TSPCs. No benefit was found in this study to include PDA coating on cell adhesion, proliferation and osteogenic differentiation of TSPCs.Conclusion The PCL/COL-1 hybrid electrospun nanofiber membranes are biocompatible, biomimetic, easily fabricated, and are capable of supporting cell adhesion, proliferation, and osteogenic differentiation of TSPCs. These bioactive electrospun nanofiber membranes may act as a suitable functional biomimetic scaffold in tendon-bone tissue engineering applications to enhance tendon-bone healing abilities.
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ACS Central Science
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2023
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IF 18.2
Ruoxi Wang,Yu Wang,Yuting Niu,Danqing He,Shanshan Jin,Zixin Li,Lisha Zhu,Liyuan Chen,Xiaolan Wu,Chengye Ding,Tianhao Wu,Xinmeng Shi,He Zhang,Chang Li,Xin Wang,Zhengwei Xie,Weiran Li,Yan Liu
Maintaining the stemness of bone marrow mesenchymal stem cells (BMMSCs) is crucial for bone homeostasis and regeneration. However, in vitro expansion and bone diseases impair BMMSC stemness, limiting its functionality in bone tissue engineering. Using a deep learning-based efficacy prediction system and bone tissue sequencing, we identify a natural small-molecule compound, dihydroartemisinin (DHA), that maintains BMMSC stemness and enhances bone regeneration. During long-term in vitro expansion, DHA preserves BMMSC stemness characteristics, including its self-renewal ability and unbiased differentiation. In an osteoporosis mouse model, oral administration of DHA restores the femur trabecular structure, bone density, and BMMSC stemness in situ. Mechanistically, DHA maintains BMMSC stemness by promoting histone 3 lysine 9 acetylation via GCN5 activation both in vivo and in vitro. Furthermore, the bone-targeted delivery of DHA by mesoporous silica nanoparticles improves its therapeutic efficacy in osteoporosis. Collectively, DHA could be a promising therapeutic agent for treating osteoporosis by maintaining BMMSC stemness.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
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IF 8.2
Qizhi Shuai,Yuxiang Liang,Xinrui Xu,Zulala Halbiyat,Xiaowan Wang,Jingwen Cheng,Jialing Liu,Tingjuan Huang,Zhiwei Peng,Lei Wang,Sheng He,Hong Zhao,Zhizhen Liu,Jun Xu,Jun Xie
A thinner endometrium has been linked to implantation failure, and various therapeutic strategies have been attempted to improve endometrial regeneration, including the use of mesenchymal stem cells (MSCs). However, low survival and retention rates of transplanted stem cells are main obstacles to efficient stem cell therapy in thin endometrium. Collagen type III is a key component of the extracellular matrix, plays a crucial role in promoting cell proliferation and differentiation, and has been identified as the major collagen expressed at the implantation site. Herein, composite alginate hydrogel containing recombinant type III collagen (rCo III) and umbilical cord mesenchymal stem cells are developed. rCo III serves as favorable bioactive molecule, displaying that rCo III administration promotes MSCs proliferation, stemness maintenance and migration. Moreover, rCo III administration enhances cell viability and migration of mouse endometrial stromal cells (ESCs). In a mouse model of thin endometrium, the Alg-rCo III hydrogel loaded with MSCs (MSC/Alg-rCo III) significantly induces endometrial regeneration and fertility enhancement in vivo. Further studies demonstrate that the MSC/Alg-rCo III hydrogel promoted endometrial function recovery partly by regulating mesenchymal-epithelial transition of ESCs. Taken together, the combination of Alg-rCo III hydrogel and MSCs has shown promising results in promoting endometrium regeneration and fertility restoration, and may provide new therapeutic options for endometrial disease.
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MOLECULAR PHARMACEUTICS
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2021
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IF 4.939
Leyi Liang,Ling Zhao,Ying Wang,Yan Wang
Mesenchymal stem cell-derived exosomes (MSC-Exos) have potential as drug-delivery vehicles and exhibit great promise for hepatocellular carcinoma (HCC) therapy. Here, we consider bone mesenchymal stem cell-derived exosomes (BMSC-Exos) as drug carriers to encase anticancer drug norcantharidin (NCTD) and explore their potential therapeutic effects against HCC. NCTD was loaded into purified exosomes from BMSCs via electroporation, and an in vitro drug release study showed that BMSC-Exos–NCTD provided a continuous and slow release of the drug. A series of in vitro and in vivo pharmacodynamic evaluations based on the HCC cell line HepG2 were conducted. The results showed that the BMSC-Exos–NCTD delivery system effectively promoted cellular uptake, induced cell cycle arrest, reduced tumor cell proliferation, increased apoptosis, and exerted obvious in vivo antitumor effects compared with the NCTD treatment alone, with BMSC-Exos–NCTD showing more significant antitumor effects. Furthermore, the in vivo detection results of the homing effect using the probe Cy5.5 showed that the BMSC-Exos carrier has an in situ homing effect on the tumor sites of HCC in mice. Moreover, BMSC-Exos–NCTD did not show body toxicity. Excitedly, BMSC-Exos–NCTD repaired damaged liver tissues in liver sections; specifically, the experimental effectiveness of the exosomes on the normal liver cell line L02 indicated that the damaged liver cells were repaired by the exosomes, as reflected by the increase in cellular proliferation and the inhibition of liver cell oxidation. Our results suggest that BMSC-Exos, as drug carriers with specific functions, have great potential in the HCC treatment in combination with anticancer drugs.
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