Stem Cell Research & Therapy
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2018
·Vol. 9
·期 1
·1-11
·
IF 4.963
Li Qiang,Yin Yating,Zheng Yuqing,Chen Feifei,Jin Peisheng
Background Increased apoptosis in adipose tissue-derived stem cells (ADSCs) limits their application in treating diabetes complications. Autophagy is a molecular process that allows cells to degrade and recover damaged macromolecules, and closely interacts with apoptosis. The aim of the present study was to investigate the potential role of autophagy in ADSC apoptosis induced by high glucose.Methods Human ADSCs were cultured in normal or high-glucose medium for 6 h, 12 h, or 24 h. The effects of high glucose on ADSC autophagy, reactive oxygen species (ROS) production, and apoptosis were evaluated. The impact of autophagy on ROS production and apoptosis was explored by treatment with rapamycin or 3-methyladenine (3-MA). The c-jun kinase (JNK) signaling pathway was investigated by pharmacological disruption of SP600125.Results ADSCs subjected to high glucose stress showed an obvious induction of autophagy and apoptosis and a significant increase in intracellular ROS levels. The JNK signaling pathway was confirmed to be involved in high glucose-induced autophagy. Pre-treatment with SP600125 or N-acetylcysteine reversed the effects of high glucose on the JNK signaling pathway and autophagy-related proteins. Pretreatment of ADSCs with 3-MA under high glucose stress induced a further increase in ROS levels compared to those of high glucose-treated cells. Furthermore, ADSCs pretreated with 3-MA under high glucose stress showed a marked increase in apoptosis compared with that of the cells treated with high glucose. Conversely, pre-treatment with rapamycin inhibited the apoptosis of ADSCs.Conclusion sTaken together, our data suggest that autophagy may play a protective role in high glucose-induced apoptosis in ADSCs. ROS/JNK signaling is essential in upregulating high glucose-induced autophagy. This study provides new insights into the molecular mechanism of autophagy involved in high glucose-induced apoptosis in ADSCs.
研究领域:
细胞生物学
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分子生物学
·
糖尿病研究
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2023
·
IF 18.9
Xiangyi Wu,Haofang Zhu,Junyi Che,Ye Xu,Qian Tan,Yuanjin Zhao
Stem cell therapies have made great progress in the treatment of diabetic wounds during recent decades, while their short in vivo residence, alloimmune reactions, undesired behaviors, and dramatic losses of cell functions still hinder the translation of them into clinic. Here, inspired by the natural components of stem cell niches, we presented novel microfluidic hydrogel microcarriers with extracellular matrix (ECM)-like composition and adipose-derived stem cells (ADSCs) encapsulation for diabetic wound healing. As the hydrogel was synthesized by conjugating hyaluronic acid methacryloyl (HAMA) onto the Fibronectin (FN) molecule chain (FN-HAMA), the laden ADSCs in the microcarriers showed improved bioactivities and pro-regenerative capabilities. Based on these features, we have demonstrated that these ADSCs microcarriers exhibited significant promotion of neovascularization, follicular rejuvenation, and collagen deposition in a mouse diabetic wound model. These results indicated that the stem cell niche-inspired FN-HAMA microcarriers with ADSCs encapsulation have great clinical potential for diabetic wound treatment.
研究领域:
生物医学工程
·
再生医学
·
组织工程
·
糖尿病研究
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DOI
PubMed
高影响因子
MACROMOLECULAR MATERIALS AND ENGINEERING
·
2018
·Vol. 303
·期 7
·1800130
·
IF 2.69
Liuyang Xuan,Ming Shi,Shuangshuang Ma,Feng Ye,Xuetao Shi,Ling Yan,Yan Li
Electrospun composite membranes in multiscale structures are developed for bone tissue engineering. Aligned polycaprolactone (PCL) fibers entrapping CA-HAp microparticles (containing CaCO 3 , hydroxyapatite, and casein in a hierarchical organization) are electrospun to find whether synergistic effects of fiber alignment and CA-HAp microparticles on improving osteogenic differentiation can be obtained. CA-HAp microparticles are in a spherical morphology of 1.42 ± 0.26 µm. Their presence increases fiber diameter and does not significantly affect fiber alignment. On all membranes, adipose derived stem cells (ADSCs) from humans spread very well. On a random group, cells distribute randomly and the presence of CA-HAp microparticles facilitates cell proliferation, especially for the one at CA-HAp/PCL 50 wt%; the one at CA-HAp/PCL 20 wt% shows significantly much higher alkaline phosphatase (ALP) activity (112.0% higher) than the pure PCL membrane. On aligned samples, cells align along fibers and expression of ALP is enhanced. However, at the same composition (CA-HAp/PCL 20 wt%), the random sample has much higher ALP activity than the aligned sample. The expressions of osteogenic marker genes are also evaluated. Combining the results and the applicability of membranes together, the random membrane at CA-HAp/PCL 20 wt% is the best candidate for bone tissue engineering.
研究领域:
材料科学
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生物医学工程
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组织工程
·
干细胞研究
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Qingyu Yu,Huizhong Hao,Weitong Wang,Linhua Zhang,Chenlu Huang,Jianying Hao,Xinyu Yang,Dunwan Zhu,Junjie Li,Hong Sun
Due to the utilization of well-defined artificial niches, stem cell culture in a three-dimensional hydrogel matrix has been a promising method for obtaining sufficient seed cells. Although various hydrogels can support desirable cell proliferation, establishing a normalized hydrogel that adequately mimics the extracellular matrix (ECM), maintains stemness and allows for controlled release of stem cells remains a significant challenge. Herein, we report a hydrogel composed of sulfobetaine-modified dextran and gelatin to maintain stemness and enable the rapid release of adipose-derived stem cells (ADSCs). Dextran can effectively maintain multipotent phenotype of ADSCs by grafting zwitterionic groups. Gelatin can significantly improve the proliferation of ADSCs. The hydrogel network they form effectively mimics the ECM microenvironment, providing an advantage when used as a three-dimensional niche to promote cell proliferation. Most importantly, the disulfide-crosslinked hydrogels show specific photodegradation capability, which precisely enables the system to achieve controlled release and efficient harvest of ADSCs. The cell viability (90 %) and harvest ratio (64 %) were well maintained by light degradation compared with GSH and collagenase degradation. Overall, this study offers a universal stem cell niche based on photodegradable hydrogel that shows great promise in the field of ADSCs proliferation and harvest.
研究领域:
生物材料学
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再生医学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Wei Liang,Jingrui Chen,Lingyan Li,Min Li,Xiaojuan Wei,Baoyu Tan,Yingying Shang,Guanwei Fan,Wei Wang,Wenguang Liu
Hydrogen sulfide (H2S) exhibits extensive protective actions in cardiovascular systems, such as anti-inflammatory and stimulating angiogenesis, but its therapeutic potential is severely discounted by the short half-life and the poorly controlled releasing behavior. Herein, we developed a macromolecular H2S prodrug by grafting 2-aminopyridine-5-thiocarboxamide (a small-molecule H2S donor) on partially oxidized alginate (ALG-CHO) to mimic the slow and continuous release of endogenous H2S. In addition, tetraaniline (a conductive oligomer) and adipose-derived stem cells (ADSCs) were introduced to form a stem cell-loaded conductive H2S-releasing hydrogel through the Schiff base reaction between ALG-CHO and gelatin. The hydrogel exhibited adhesive property to ensure a stable anchoring to the wet and beating hearts. After myocardial injection, longer ADSCs retention period and elevated sulfide concentration in rat myocardium were demonstrated, accompanied by upregulation of cardiac-related mRNA (Cx43, α-SMA, and cTnT) and angiogenic factors (VEGFA and Ang-1) and downregulation of inflammatory factors (tumor necrosis factor-α). Echocardiography and histological analysis strongly demonstrated an increase in the ejection fraction value and smaller infarction size, suggesting a remarkable improvement of the cardiac functions of Sprague-Dawley rats. The ADSC-loaded conductive hydrogen sulfide-releasing hydrogel dramatically promoted the therapeutic effects, offering a promising therapeutic strategy for treating myocardial infarction.
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2023
·
IF 6.8
Yi He,Fangyang Shi,Jiajun Hu,Hongyu Li,Xun Chen,Lingyu Yuan,Yunyang Lu,Weidong Du,Runze Li,Jie Wu,Feilong Deng,Dongsheng Yu
Magnetic graphene oxide nanocomposites (MGO NPs) have been widely studied in biomedical applications. However, their cytotoxicity and underlying mechanisms remain unclear. In this study, the biosafety of MGO NPs was investigated, and the mechanism involved in ferroptosis was further explored. MGO can produce cytotoxicity in ADSCs, which is dependent on their concentration. Ferroptosis was involved in MGO NP-induced ADSC survival inhibition by increasing total ROS and lipid ROS accumulation as well as regulating the expression levels of ferroptosis-related genes and proteins. GPX4 played a critical role in the MGO NP-induced ADSC ferroptosis process, and overexpressing GPX4 suppressed ferroptosis to increase cell survival. This study provides a theoretical basis for the biosafety management of MGO NPs used in the field of biomedical treatment.
研究领域:
纳米技术
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生物医学工程
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细胞生物学
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毒理学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Jiaye Li,Fengyuan Wang,Youjun Ding,Guopu Chen,Qian Tan,Yuanjin Zhao
Adipose-derived stem cells (ADSCs) have proven to be valuable in chronic wounds treatment, while their applications often suffer from low survival rates in complex wound environments. Here, we developed a novel biomimetic extracellular matrix (ECM)-like chondroitin sulfate (ChS) hydrogel loaded with ADSCs and polydopamine nanoparticles (PDA NPs) to accelerate chronic wound healing. We have demonstrated that the ChS-based hydrogel could mimick ECM, promoting cell proliferation and migration, and the PDA NPs exhibited antioxidative and antibacterial effects. Thus, the hybrid hydrogel was identified to promote diabetic wound healing by supporting ADSCs’ survival, enhancing angiogenesis, re-epithelialization, and reducing inflammation. These results indicated that our proposed ADSCs and PDA integrated biomimetic ECM-like hydrogel had practical significance in treating chronic wounds and different clinical diseases.
研究领域:
生物材料学
·
再生医学
·
组织工程
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产品关联
DOI
高影响因子
BIOMATERIALS
·
2013
·
IF 7.604
Jinbao Qin,Kangan Li,Chen Peng,Xiangxiang Li,Jiaying Lin,Kaichuang Ye,Xinrui Yang,Qingsong Xie,Zunli Shen,Yuqing Jin,Mier Jiang,Guixiang Zhang,Xinwu Lu
Adipose-derived stem cells (ADSCs) exhibit tremendous potential for repair of ischemic diseases. However, studies on the fate, migration, differentiation, and body distribution of the labeled ADSCs are rarely reported. In this study, magnetic iron oxide nanoparticles were designed, synthesized, and coated with meso-2,3-dimercaptosuccinic acid (DMSA) to produce DMSA nanoparticles (DMSA-NPs). The properties, size distribution, and characterization of DMSA-NPs were evaluated. Green fluorescent protein expressing ADSCs (GFP-ADSCs) were obtained and labeled with DMSA-NPs. The viability, cytotoxicity and multi-differentiation capacity of labeled GFP-ADSCs were evaluated in vitro. Labeled and non-labeled GFP-ADSCs were injected into a mouse model of hindlimb ischemia, and 3T magnetic resonance imaging (MRI) was acquired. The synthesized DMSA-NPs efficiently labeled the GFP-ADSCs in vitro and in vivo without affecting cell viability , proliferation, cell cycle, and multi-differentiation capacity. The MRI showed hypointense spots in the labeled GFP-ADSCs that lasted up to 8 weeks. Prussian blue staining and immunofluorescence assay at 4 and 8 weeks indicated that the labeled GFP-ADSCs were in and around the ischemic sites and some differentiated into capillaries. This observation is identical to that seen for transplants of unlabeled cells. Labeled cells were also identified mainly in the liver and spleen, with significantly smaller amounts in the lungs, intestines, heart, and kidney. Developed DMSA-NPs were shown to exhibit a considerable potential for use as nanoprobes for MRI of stem cells, which will enhance our understanding of cell-based therapeutic strategies for ischemic diseases.
研究领域:
医学
·
生物技术
·
影像学
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DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2021
·Vol. 8
·期 3
·
IF 6.353
Wu Yu,Liang Tangzhao,Hu Ying,Jiang Shihai,Luo Yuansen,Liu Chang,Wang Guo,Zhang Jing,Xu Tao,Zhu Lei
Severe burns are challenging to heal and result in significant death throughout the world. Adipose-derived mesenchymal stem cells (ADSCs) have emerged as a promising treatment for full-thickness burn healing but are impeded by their low viability and efficiency after grafting in vivo. Nitric oxide (NO) is beneficial in promoting stem cell bioactivity, but whether it can function effectively in vivo is still largely unknown. In this study, we bioprinted an efficient biological scaffold loaded with ADSCs and NO (3D-ADSCs/NO) to evaluate its biological efficacy in promoting severe burn wound healing. The integral 3D-ADSCs/NO hydrogel scaffolds were constructed via 3D bioprinting. Our results shown that 3D-ADSCs/NO can enhance the migration and angiogenesis of Human Umbilical Vein Endothelial Cells (HUVECs). Burn wound healing experiments in mice revealed that 3D-ADSCs/NO accelerated the wound healing by promoting faster epithelialization and collagen deposition. Notably, immunohistochemistry of CD31 suggested an increase in neovascularization, supported by the upregulation of vascular endothelial growth factor (VEGF) mRNA in ADSCs in the 3D biosystem. These findings indicated that 3D-ADSC/NO hydrogel scaffold can promote severe burn wound healing through increased neovascularization via the VEGF signalling pathway. This scaffold may be considered a promising strategy for healing severe burns.
研究领域:
生物医学工程
·
组织工程
·
创伤愈合
·
干细胞生物学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Hanbang Chen,Yunzhu Qian,Yang Xia,Gang Chen,Yun Dai,Na Li,Feimin Zhang,Ning Gu
The topographical features and material composition of scaffolds have a powerful influence on cell behaviors such as proliferation and differentiation. Here, scaffolds consisting of aligned fibers with incorporated bioactive collagen I were tested for their ability to enhance osteogenesis in vitro. Rat adipose-derived mesenchymal stem cells (ADSCs) were seeded on the scaffolds and their morphology, proliferation, and osteogenic differentiation were examined. Aligned scaffolds with collagen I showed the best osteogenic properties. Also, adhesion-related genes showed the higher expression on aligned scaffolds with collagen I. Our findings indicate that fiber alignment combined with incorporation of collagen I increases the capacity of electrospun scaffolds to induce enhanced and directed osteogenesis. Such scaffolds may, therefore, have potential for improving guided oral bone regeneration.
研究领域:
组织工程
·
再生医学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Zhonglian Wu,Jian Yang,Hui Chong,Xiaomei Dai,Haidi Sun,Junli Shi,Meijuan Yuan,Dianwei Liu,Mengbo Dang,Hang Yao,Wen-Yong Fei
Rotator cuff tear repair poses significant challenges due to the complex gradient interface structure. In the face of disease-related disruptions in the tendon-bone interface (TBI), the strategy of constructing a biomimetic scaffold is a promising avenue. A novel 3D-printed rotator cuff scaffold loaded adipose stem cells (ADSCs), bone morphogenetic protein-2 (BMP-2), and collagen type I (COL I). The efficiency of the slow-release BMP-2 design depended on the dopamine-hyaluronic acid (HAD) and BMP-2 reaction. The cumulative release of BMP-2 was 44.97% ± 5.45% at 4 weeks. The 3D-printed bilayer scaffold, incorporating COL I and BMP-2, effectively promoted the differentiation of ADSCs into osteogenic, tenogenic, and chondrogenic lineages in vitro. The combination of 3D-printed bioactive scaffolds and ADSCs demonstrated a superior repair effect on rotator cuff injuries in vivo. Therefore, these findings indicated that the 3D-printed biomimetic scaffold loaded with ADSCs and BMP-2 holds potential as a promising graft for TBI healing.
研究领域:
生物医学工程
·
组织工程
·
再生医学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 31
·6912-6924
·
IF 5.344
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
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）