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Journal of Materials Chemistry B · 2020 ·Vol. 8 ·期 31 ·6912-6924 · IF 5.344

Calcium alendronate-coated composite scaffolds promote osteogenesis of ADSCs via integrin and FAK/ERK signalling pathways

Lei Liu,Xianling Gao,Xiaoyu Li,Guanglin Zhu,Nanying Li,Xuetao Shi,Yingjun Wang

Bioceramic–biopolymer composites have been used extensively as bone tissue engineering scaffolds due to their bioactive properties. However, composite scaffolds are insufficient in inducing osteogenic differentiation of stem cells. In this study, a strategy for the local delivery of bioactive factors by coating calcium alendronate (ALC) on the surface of composite scaffolds was systematically evaluated for the first time. The coated ALC not only displayed excellent cytocompatibility and cell adhesion properties but also resulted in the significant upregulation of osteogenic related gene expression, osteogenic related protein levels, alkaline phosphatase (ALP) activity and calcium deposition of ADSCs. Furthermore, our results suggested that the molecular mechanism of ADSC osteogenic differentiation induced by the constructed ALC may be related to the integrin binding and the activation of FAK/ERK signalling pathways. These findings suggested that ALC-coated composite scaffolds can serve as bone tissue engineering scaffolds, providing a simple and universal method to improve the osteogenic differentiation of ADSCs by calcium phosphate-containing composite materials.

研究领域: 组织工程 · 生物材料 · 干细胞生物学
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Molecular Metabolism · 2025 · IF 6.6

High-Fat Diet Induces Senescence in ADSCs via CDK4 Ubiquitination-Mediated Cell Cycle Disruption, Contributing to Impaired Glucose Tolerance

Zheng Ge,Zitian Liu,Shuohui Dong,Xiang Zhao,Guangwei Yang,Ao Yu,Wei Guo,Xiang Zhang,Qunzheng Wu,Kexin Wang

High-fat diet (HFD) promotes adipose tissue senescence, which in turn disrupts insulin-mediated glycemic homeostasis. The underlying mechanisms remain unclear. Through clinical survey data, animal models, and primary adipose-derived mesenchymal stem cells (ADSC), we investigated how dietary patterns influence adipocyte senescence. We found that elevated fatty acid levels enhance the interaction between the E3 ubiquitin ligase TRIP12 and Cyclin-dependent kinase 4 (CDK4) in ADSCs, triggering CDK4 ubiquitination and degradation. As a process associated with this disruption in cell cycle progression, cellular senescence may represent a key outcome. Consequently, senescent ADSC-derived mature adipocytes (ADSC-MA) exhibit impaired insulin-stimulated GLUT4 membrane translocation and reduced glucose uptake. In contrast, within an HFD setting, dietary fiber supplementation is associated with the reversal of cellular senescence. The gut microbiota–short-chain fatty acids (SCFAs) axis may be involved in the restoration of cell cycle progression and the amelioration of ADSC senescence, correlating with a partial recovery of glucose uptake capacity in ADSC-MAs. Our study highlights potential strategies to reverse cellular senescence and identifies promising therapeutic targets for impaired glucose tolerance.

研究领域: 内分泌学 · 细胞生物学 · 代谢学 · 分子生物学 · 营养科学
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Advanced Healthcare Materials · 2022 ·Vol. 12 ·期 3 ·2201925 · IF 11.092

Swelling-Mediated Mechanical Stimulation Regulates Differentiation of Adipose-Derived Mesenchymal Stem Cells for Intervertebral Disc Repair Using Injectable UCST Microgels

Xianpeng Huang,Di Chen,Chengzhen Liang,Kesi Shi,Xiaopeng Zhou,Yuang Zhang,Yi Li,Jiangjie Chen,Kaishun Xia,Jiawei Shu,Biao Yang,Jingkai Wang,Haibin Xu,Chao Yu,Feng Cheng,Shaoke Wang,Yongxiang Zhang,Chenggui Wang,Liwei Ying,Hao Li,Meiling Han,Fangcai Li,Yiqing Tao,Qian Zhao,Qixin Chen

Mechanical stimulation is an effective approach for controlling stem cell differentiation in tissue engineering. However, its realization in in vivo tissue repair remains challenging since this type of stimulation can hardly be applied to injectable seeding systems. Here, it is presented that swelling of injectable microgels can be transformed to in situ mechanical stimulation via stretching the cells adhered on their surface. Poly(acrylamide- co -acrylic acid) microgels with the upper critical solution temperature property are fabricated using inverse emulsion polymerization and further coated with polydopamine to increase cell adhesion. Adipose-derived mesenchymal stem cells (ADSCs) adhered on the microgels can be omnidirectionally stretched along with the responsive swelling of the microgels, which upregulate TRPV4 and Piezo1 channel proteins and enhance nucleus pulposus (NP)-like differentiation of ADSCs. In vivo experiments reveal that the disc height and extracellular matrix content of NP are promoted after the implantation with the microgels. The findings indicate that swelling-induced mechanical stimulation has great potential for regulating stem cell differentiation during intervertebral disc repair.

研究领域: 组织工程 · 干细胞生物学 · 生物医学工程 · 骨科
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Biomaterials Science · 2021 ·Vol. 10 ·期 3 ·808-818 · IF 6.843

Labelling stem cells with a nanoprobe for evaluating the homing behaviour in facial nerve injury repair

Na Tang,Xueyi Wang,Jin Zhu,Kang Sun,Shiting Li,Ke Tao

It is crucial and clinically relevant to clarify the homing efficiency and retention of stem cells in different implanting strategies of cell therapy for various injuries. However, the need for a tool for investigating the mechanisms is still unmet. We herein introduce multi-modal BaGdF5:Yb,Tm nanoparticles as a nanoprobe to label adipose-derived stem cells (ADSCs) and detect the homing behavior with a micro-computed tomography (micro-CT) imaging technique. The migration of cells injected locally or intravenously, with or without a chemokine, CXCL 12, was compared. A higher homing efficiency of ADSCs was observed in both intravenously injected groups, in contrast to the low efficiency of cell retention in local implantation. Meanwhile, CXCL 12 promoted the homing of ADSCs, especially in the intravenous route. Nonetheless, the administration of CXCL 12 showed its therapeutic efficacy, whereas intravenous injection of ADSCs almost did not. Our work provided a tool for in vivo imaging of the behavior of implanted cells in preclinical studies of cell therapy, and more importantly, implied that the parameters for implanting stem cells in clinical operation should be carefully considered.

CAS / MDL: 76-05-1
研究领域: 生物医学工程 · 干细胞研究 · 神经科学 · 医学影像
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Stem Cell Research & Therapy · 2019 ·Vol. 10 ·期 1 ·1-11 · IF 4.627

Antioxidants inhibit cell senescence and preserve stemness of adipose tissue-derived stem cells by reducing ROS generation during long-term in vitro expansion

Liao Naishun,Shi Yingjun,Zhang Cuilin,Zheng Youshi,Wang Yingchao,Zhao Bixing,Zeng Yongyi,Liu Xiaolong,Liu Jingfeng

Background Adipose tissue-derived mesenchymal stem cells (ADSCs) are promising candidates for regenerative medicine. However, long-term in vitro passaging leads to stemness loss and cell senescence of ADSCs, resulting in failure of ADSC-based therapy. Methods In this study, ADSCs were treated with low dose of antioxidants (reduced glutathione and melatonin) with anti-aging and stem cell protection properties in the in vitro passaging, and the cell functions including stem cell senescence, cell migration, cell multidirectional differentiation potential, and ROS content were carefully analyzed. Results We found that GSH and melatonin could maintain ADSC cell functions through reducing cell senescence and promoting cell migration, as well as by preserving stemness and multidirectional differentiation potential, through inhibiting ROS generation during long-term expansion of ADSCs. Conclusions Our results suggested that antioxidant treatment could efficiently prevent the dysfunction and preserve cell functions of ADSCs after long-term passaging, providing a practical strategy to facilitate ADSC-based therapy.

CAS / MDL: 70-18-8 73-31-4
研究领域: 再生医学 · 干细胞生物学 · 细胞衰老 · 氧化应激
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Materials Today Bio · 2023 · IF 8.2

Injectable hyperbranched PEG crosslinked hyaluronan hydrogel microparticles containing mir-99a-3p modified subcutaneous ADSCs-derived exosomes was beneficial for long-term treatment of osteoarthritis

Zhaowei Yin,Chaoren Qin,Shaowei Pan,Chen Shi,Guanfu Wu,Yan Feng,Jing Zhang,Ziyi Yu,Bin Liang,Jianchao Gui

Exosomes (Exos) secreted by adipose-derived stem cells (ADSCs) have shown potential in alleviating osteoarthritis (OA). Previous studies indicated that infrapatellar fat pad (IPFP) derived stem cells (IPFSCs) may be more suitable for the treatment of OA than subcutaneous adipose tissue (ScAT) derived stem cells (ScASCs). However, it remains unclear which type of Exos offers superior therapeutic benefit for OA. This study first compared the differences between Exos derived from IPFP stem cells (Exos IPFP ) and ScAT stem cells (Exos ScAT ) in OA treatment. Results suggested that Exos IPFP significantly inhibit the degradation of cartilage extracellular matrix (ECM) than Exos ScAT , following this, the differences in microRNA (miRNA) expression between the two types of Exos using small RNA sequencing were performed. Subsequently, miR-99 b-3p was chosen and over-expressed in Exos ScAT (Exos ScAT−99b−3p ), both in vivo and in vitro experiments demonstrated its efficacy in inhibiting the expression of ADAMTS4, promoting the repair of the ECM in OA. Finally, microfluidic technology was performed to fabricate a hyaluronan-based hydrogel microparticles (HMPs) for encapsulating Exos (HMPs@exos), the injectability, sustained release of Exos and long-term therapeutic effect on OA were validated. In summary, these results suggest miR-99 b-3p regulates the degradation of cartilage ECM by targeting ADAMTS4, the upregulation of miR-99 b-3p in Exos ScAT would enable them to exhibit comparable or even superior effectiveness to Exos IPFP for OA treatment, making it a promising approach for OA treatment. Considering the abundant resources of ScAT and the limited availability of IPFP, ScAT harvested through liposuction could be genetically engineered to yield Exos for OA treatment. Furthermore, the encapsulation of Exos in HMPs provides an injectable sustained local drug release system, which could potentially enhance the efficacy of Exos and hold potential as future therapeutic strategies.

研究领域: 生物材料 · 干细胞治疗 · 基因治疗 · 骨科 · 药学
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Materials Futures · 2024 ·Vol. 3 ·期 3 ·035403 · IF 12

rADSC-loaded tubular units composed of multilayer electrospun membranes promoted bone regeneration of critical-sized skull defects

Huamin Jiang,Zhaoyi Lin,Jinze Li,Ting Song,Hongyun Zang,Pengwen Li,Jiarun Li,Wenyi Hou,Jianhua Zhou,Yan Li

Adipose-derived stem cells (ADSCs) have considerable potential for bone regeneration. However, their performance is limited by a lack of scaffolds that adequately mimic the hierarchical structure of bone to promote proliferation and osteogenic differentiation of ADSCs. In this study, nanofiber membranes composed of polycaprolactone, poly(lactide-co-glycolide), and hydroxyapatite (HAp) were prepared via electrospinning, and the membranes curled after responding to temperature stimuli in an aqueous solution. Transmission electron microscopy and scanning electron microscopy observations indicated that needle-like HAp nanoparticles with an average diameter of 57 ± 39 nm and a length–diameter ratio of 7.4 ± 1.56 were entrapped in the nanofiber matrix and did not affect the surface morphology of fibers. After cutting and deformation, the nanofibers changed from straight to bent, and the diameters increased; they were 1105 ± 200 nm for BPLG85-H and 1120 ± 199 nm for BPLG80-H. Additionally, tubular units with a single layer (BPLG-H(1.5)) or multiple layers (BPLG-H(3.5)) were obtained by controlling the initial shape and size of the membranes. rADSCs on the concave surface of BPLG-H(3.5) proliferated faster and exhibited better osteogenic activity than those on the convex side of BPLG-H(3.5) and both surfaces of BPLG-H(1.5), which was correlated with the higher expressions of vascular endothelial growth factor and bone morphogenetic protein 2. Additionally, rADSCs on both units maintained osteogenic activity after storage at -80 °C for 20 d. In rat skull defect (diameter of 8 mm) models, rADSC-loaded BPLG-H(3.5) units fixed using gelatin hydrogel (ADSC@BHM) exhibited 84.1 ± 6.6% BV/TV after implantation for 12 weeks, which was 155.6% higher than that of the Blank group. H&E and Masson's staining results demonstrated that there was more bone regeneration at the defect center of ADSC@BHM than in the BHM and Blank groups. In conclusion, rADSC-loaded BPLG-H(3.5) with an osteon-mimic structure provides a potential strategy to repair bone defects.

CAS / MDL: 920-66-1
研究领域: 组织工程 · 再生医学 · 生物材料科学 · 生物医学工程
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CARBOHYDRATE POLYMERS · 2023 · IF 11.2

A multi-functional double cross-linked chitosan hydrogel with tunable mechanical and antibacterial properties for skin wound dressing

Fengling Liu,Lu Wang,Xinrang Zhai,Shunxian Ji,Jingjia Ye,Zhiqiang Zhu,Chong Teng,Wei Dong,Wei Wei

Chitosan hydrogels with essential antibacterial properties and biocompatibility have great potential in tissue engineering and regeneration medicine. However, pure chitosan hydrogel could be limited by insufficient mechanical properties. In this work, we designed a multi-functional chitosan hydrogel based on the combination of chitosan methacrylate (CTSMA) and sulfhydrated chitosan (CTSSH), which is cross-linked simultaneously by free-radical polymerization reaction and Thiol-ene reaction. The CTSMA/CTSSH (CMS) hydrogels displayed superior tissue adhesive and mechanical properties when compared to pure CTSMA hydrogel. Additionally, the resulting hydrogels exhibited potent antimicrobial effects against both E. coli and S. aureus . Besides, the CMS hydrogels exhibited good biocompatibility as demonstrated by cytotoxicity and cell proliferation experiments using fibroblasts cells (L929) and adipose-derived stem cells (ADSCs). In vivo experiment, the repairing effect of hydrogels on full-thickness skin defect model in rats was studied. Histological and immunohistochemical staining results showed that CMS hydrogels promoted angiogenesis , dermal repair and epidermal regeneration. Overall, the study highlights the potential of the CMS hydrogels as a promising biomaterial in wound healing applications.

研究领域: 生物材料 · 组织工程 · 伤口愈合 · 生物医学工程 · 材料科学
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