CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Yingbo Shen,Rui Liu,Xiangyi Wu,Ying Lu,Bin Kong,Yuanjin Zhao
Mesenchymal stem cells (MSCs) loaded hydrogels have shown positive therapeutic effects in skin wound treatment, while their application is still impractical on the wound bed. Here, we propose novel MSCs-loaded self-healing hydrogel microfiber fragments from microfluidic bubbles interrupted spinning for wound healing. The hydrogel microfibers are composed of sodium alginate, gelatin, polyvinyl alcohol, and borax, vesting them with good biocompatibility and self-healing ability. Their fragments with adjustable length are generated by introducing bubbles into microfluidic channels. We have demonstrated that the self-healing microfibers can promote the proliferation of MSCs, which are seeded alongside fragments’ surfaces to further facilitate the wound healing process. In addition, these MSCs laden self-healing hydrogel microfibers (MSG-fibers) showed obvious healing effect in rat wound model, which significantly promoted granulation tissue formation, collagen deposition and vascular construction at the wound site. Thus, we believe that our proposed MSC-laden microfiber fragments are valuable in promoting wound healing and have promising prospect in becoming new options for wound management.
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Hongxiu Yuan,Gang Wang,Fangbo Zou,Peifen Lu,Noshin Afshan,Jianwei Jiao,Jin Jiao
Therapeutic strategies that can target multilevel immunoregulatory pathways in inflammatory bowel disease (IBD) and efficiently target the site of inflammation are expected to greatly enhance the therapeutic efficacy. Here, we have developed a DNA nanorobot-armed bidirectional resistant mesenchymal stem cell (MSC) for IBD treatment, which blocks lymphocyte infiltration at the site of inflammation by bidirectional inhibition of integrin-ligand inter-recognition via resistant aptamer-hands. And this strategy can induce MSC homing for immunomodulation and tissue repair. Herein, in this nanorobot, tetrahedral DNA (TDN) serves as a communication bridge, Integrin α4 and VCAM 1 aptamers are equipped to two vertices of TDN, and the other two cholesterol vertices of TDN are used for immobilization on MSC. In murine colitis models, tail vein-injected resistant MSC preferentially and rapidly accumulated in the inflamed colon and have been more effective in reducing colonic inflammation than pure MSC or aptamers bidirectional inhibitors. The therapeutic strategy proposed in this work has minimal systemic side effects and holds therapeutic promise for a subgroup of IBD patients who do not respond to single anti-inflammatory therapies.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
·
2019
·Vol. 234
·期 9
·16312-16319
·
IF 4.522
Danyang Yue,Mengxue Zhang,Juan Lu,Jin Zhou,Yuying Bai,Jun Pan
We have previously demonstrated that the rate of fluid shear stress (ΔSS) can manipulate the fate of mesenchymal stem cells (MSCs) to osteogenic or chondrogenic cells. However, whether ΔSS is comparable to other two means of induction medium and substrate stiffness that have been proven to be potent in differentiation control is unknown. In this study, we subjected MSCs to 1–7 days of osteogenic or chondrogenic chemical induction, or 1–4 days of 37 or 86 kPa of substrate stiffness induction, followed by 20 min of Fast ΔSS (0–0′) or Slow ΔSS (0–2′), which is a laminar FSS that linearly increased from 0 to 10 dyn/cm 2 in 0 (Fast) or 2 min (Slow) and maintained at 10 dyn/cm 2 for a total of 20 min. We found that 20 min of ΔSS could compete with 5 days' chemical and 2 days' substrate stiffness inductions. Our study confirmed that ΔSS is a powerful tool to control the differentiation of MSCs, which stressed the possible application in MSCs linage specification.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Liuxin Yang,Dandan Wei,Yinghua Tao,Fengya Jing,Tao Liu,Guanhua Jiao,Tianzhu Zhang
Healing the wounds of abdominal wall defects characterised by severe complications represents a significant clinical challenge. Mesenchymal stem cells (MSC)-based therapies have emerged as a promising strategy for tissue regeneration. However, the low engraftment and survival rates limit their application owing to the complicated wound microenvironment and large wound areas in abdominal wall defects. Inspired by focal biointerfaces, the present research engineered a spatiotemporal delivery microenvironment-responsive therapeutic platform, termed MSC-GSM@HG, for abdominal wall repair. The constructed platform proved capable of dissolving HA-PBA/Gel-DA (HG) hydrogels in response to in vivo inflammatory responses and subsequently releasing MSC-laden gelatine and silk fibroin microspheres (GSMs). Meanwhile, the HG hydrogels can not only protect the MSCs from excessive reactive oxygen species but also exhibit haemostatic and anti-inflammatory properties. Strikingly, this microsphere-releasing hydrogel platform actively enhanced the repair of abdominal wall defects in vivo , by reducing inflammatory response, facilitating angiogenesis and promoting collagen deposition. Therefore, the microenvironment-responsive platform represents a promising strategy for MSC-based therapies for abdominal wall defects through spatiotemporal delivery mechanisms.
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Yuqin Chen,Wei Lv,Jiangna Xu,Shengnan Li,Kefan Song,Yue Gong,Wei Zhao,Hongli Liu,Zhenwei Ding,Linfeng Liu,Jiaqing Yin,Dan Su,Ming Lu,Xiangming Fang,Hongliang Xin
Excessive accumulation of reactive oxygen species (ROS) in Parkinson's disease (PD) leads to oxidative stress, which induces neuroinflammation and accelerates disease progression. To address this, we developed mPDA@MSC, a nanosystem consisting of mesoporous polydopamine (mPDA) nanoparticles coated with a mesenchymal stem cell membrane (MSCm), which exhibits ROS-scavenging properties. The mPDA structure significantly enhanced ROS-scavenging and anti-inflammatory activities, while the surface-encapsulated MSCm enabled effective blood-brain barrier traversal and targeted the lesion site in the PD brain. Both in vitro and in vivo studies demonstrated that mPDA@MSC exerted anti-Parkinsonian effects through multiple mechanisms, including ROS scavenging, modulation of mitochondrial dysfunction, and promotion of the transition from pro-inflammatory to anti-inflammatory microglial phenotypes. This resulted in the reversal of dopaminergic neuron damage, inhibition of α-synuclein (α-syn) production, and improvement in behavioral deficits and other phenotypes. These findings highlight the potential of mPDA@MSC as a therapeutic agent for PD and introduce a novel approach to anti-PD therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Stem Cell Research & Therapy
·
2025
·Vol. 16
·期 1
·1-21
·
IF 7.3
Liao Guolong,Long Canling,Guo Rui,Wang Sushan,Han Ruijuan,Yang Jianhua,Liu Jia
Background Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition characterized by debilitating pelvic pain. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are recognized as pivotal mediators of MSCs’ paracrine activity and represent a novel therapeutic approach for IC/BPS. However, their efficacy is hindered by the inherent variability of primary MSCs (pMSCs) from different donors and their susceptibility to senescence during culture expansion.Methods To overcome these challenges, we developed conditionally immortalized mesenchymal stem cells (iMSCs) using a doxycycline-regulated simian virus 40 Large T expression system in pMSCs. The conditioned proliferation capacity of iMSCs was evaluated using cell counting and immunocytochemistry. The expression of surface markers on iMSCs was assessed by flow cytometry. The osteogenic and adipogenic differentiation capabilities of iMSCs at different population doubling (PD) numbers were analyzed by qPCR, alizarin red staining, and oil red O staining. The EVs secreted by iMSCs were characterized using Western blot, scanning electron microscopy, and particle size analysis. In vitro and in vivo bladder inflammation models were used to evaluate the therapeutic effects of EVs on IC/BPS.Results These iMSCs exhibited precisely controlled proliferation, maintained surface marker expression and differentiation capacities, comparable to pMSCs up to PD 40. The characteristics of iMSC-EVs are equivalent to those of pMSCs. Furthermore, in vitro cellular experiments demonstrate that iMSC-EVs provide protective effects against LPS/ATP-induced damage in SV-HUC-1 cells. Additionally, administration of iMSC-EVs significantly enhanced tissue healing and anti-inflammatory capabilities in an IC/BPS animal model.Conclusion sIn summary, this approach produced a reliable source of functional MSCs and EVs, with iMSC-EVs demonstrating robust immunomodulatory properties and promoting tissue healing in IC/BPS. This method represents a promising alternative to pMSCs for IC/BPS therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Biomedical Engineering
·
2025
·
IF 26.6
Xu Saijuan,Liang Dan,Wang Qiudao,Cheng Yan,Xie Da,Gui Yang,Zhang Haokun,Feng Changrui,Zhao Feiyan,Ren Wendan,Sun Gongrui,Yang Yang,Li Lin,Lai Yongrong,Fu Bin,Lu Yuming,Wang Zi Jun,Wu Yuxuan
Ex vivo autologous haematopoietic stem cell (HSC) gene therapy provides a promising treatment option for haematological disorders. However, current methods involve complex processes and chemotherapeutic conditioning, leading to limited accessibility for treatment and major side effects. Here we develop antibody-free targeted lipid nanoparticles (LNPs) for mRNA delivery to HSCs in vivo, enabling efficient base editing of the γ-globin gene ( HBG1/2 ) promoter target in human HSCs to reactivate fetal haemoglobin in derived erythroid cells. Delivery of ABE8e/sgRNA mRNA with optimized LNPs achieves efficient in vivo base editing of HBG1/2 in transfusion-dependent β-thalassaemia (TDT) patient-derived HSCs engrafted in immunodeficient NCG-X mice, showing restored globin chain balance in erythroid cells. Our research indicates that using LNPs for genome editor delivery achieves efficient editing of endogenous genes of human HSCs. This non-viral delivery system eliminates the need for collecting or mobilizing HSCs, providing a potent and one-time treatment potential for blood disorders such as sickle cell disease and TDT.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Xuan Jiang,Manli Wang,Guoliang Cui,Yuanyuan Wu,Zhonghong Wei,Suyun Yu,Aiyun Wang,Wei Zou,Yanhong Pan,Xiaoman Li,Yin Lu
Background Tetramethylpyrazine (TMP), a key bioactive constituent derived from Ligusticum wallichii Franchat , has demonstrated efficacy in mitigating multidrug resistance (MDR) in human breast cancer (BC) cells. However, the precise mechanisms underlying its action remain poorly understood. Purpose Cancer stem cells (CSCs) are widely recognized as the primary contributors to MDR. This investigation seeks to elucidate the role and mechanisms through which TMP counteracts MDR by attenuating CSC-like characteristics. Methods Various assays, including flow cytometry, sphere formation, and Western blotting, were employed to evaluate TMP's effects on breast cancer stem cell (BCSC)-like phenotypes in vitro. In vivo , extreme limiting dilution assays and immunohistochemistry (IHC) were executed to assess the impacts of TMP on BCSC frequency and the levels of stemness markers. Mechanistically, RNA sequencing was performed to uncover the key biological processes involved in TMP's effects on BCSCs. Further experiments, encompassing micro scale thermophoresis (MST), drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA) and amino acid mutation analyses, were utilized to identify the essential targets and corresponding binding sites of TMP. Finally, the effects of TMP on BCSC-like phenotypes were confirmed using cells with mutated amino acid residues, which allowed us to investigate the specificity of TMP's binding sites. To further evaluate the impact of TMP on drug resistance, doxorubicin-resistant MCF7 (MCF-7 ADR ) cells, along with corresponding cell lines harboring mutated amino acid residues, were employed. Results TMP was found to inhibit BCSC-like properties both in vitro and in vivo , evidenced by a reduction in the CD44 + /CD24 - population, sphere formation capability, and expression of stemness markers. Mechanistic studies revealed that TMP targets 3‑hydroxy-3-methylglutaryl-CoA reductase (HMGCR), a rate-limiting enzyme in cholesterol biosynthesis. TMP binds to Asp-767 of HMGCR, thereby inhibiting its activity and reducing cholesterol synthesis. The influence of TMP on BCSC-like phenotypes was nullified by overexpression of wild-type HMGCR, while mutations in the binding site of HMGCR had no effect on TMP's inhibition of BCSC-like properties. Additionally, TMP mitigated MDR by targeting HMGCR. Conclusion These findings suggest that TMP alleviates MDR by reducing BCSC-like traits through targeting HMGCR and disruption of cholesterol biosynthesis in BC. This provides new insights into the mechanisms through which TMP alleviates MDR and offers new lead compound for exploring HMCGR antagonists.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Javad Harati,Ping Du,Massimiliano Galluzzi,Xian Li,Jiao Lin,Haobo Pan,Peng-Yuan Wang
The extracellular matrix (ECM) shapes the stem cell fate during differentiation by exerting relevant biophysical cues. However, the mechanism of stem cell fate decisions in response to ECM-backed complex biophysical cues has not been fully understood due to the lack of versatile ECMs. Here, we designed two versatile ECMs using colloidal self-assembly technology to probe the mechanisms of their effects on mechanotransduction and stem cell fate regulation. Binary colloidal crystals (BCC) with a hexagonally close-packed structure, composed of silica (5 μm) and polystyrene (0.4 μm) particles as well as a polydimethylsiloxane-embedded BCC (BCCP), were fabricated. They have defined surface chemistry, roughness, stiffness, ion release, and protein adsorption properties, which can modulate the cell adhesion, proliferation, and differentiation of human adipose-derived stem cells (hASCs). On the BCC, hASCs preferred osteogenesis at an early stage but showed a higher tendency toward adipogenesis at later stages. In contrast, the results of BCCP diverged from those of BCC, suggesting a unique regulation of ECM-dependent mechanotransduction. The BCC-mediated cell adhesion reduced the size of the focal adhesion complex, accompanying an ordered spatial organization and cytoskeletal rearrangement. This morphological restriction led to the modulation of mechanosensitive transcription factors, such as c-FOS, the enrichment of transcripts in specific signaling pathways such as PI3K/AKT, and the activation of the Hippo signaling pathway. Epigenetic analyses showed changes in histone modifications across different substrates, suggesting that chromatin remodeling participated in BCC-mediated mechanotransduction. This study demonstrates that BCCs are versatile artificial ECMs that can regulate human stem cells’ fate through unique biological signaling, which is beneficial in biomaterial design and stem cell engineering.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Exploration
·
2025
·
IF 22.5
Qingyuan Deng,Ao Hua,Shiyou Li,Zhijie Zhang,Xiang Chen,Qiang Wang,Xing Wang,Zhiqin Chu,Xiangliang Yang,Zifu Li
An extracellular acidic environment and an intracellular mildly alkaline environment induced by carbonic anhydrase 9 (CA9) play a critical role in self-renewal, invasion, migration, and drug resistance of cancer stem cells (CSCs) within hypoxic solid tumors. Here, we report an antitumor strategy leveraging hyperbaric oxygen therapy (HBO) to regulate tumor pH and boost hydroxyethyl starch-doxorubicin-copper nanoparticles (HHD-Cu NPs) against CSCs. HBO overcomes tumor hypoxia, downregulates pH-regulatory proteins such as CA9, and leads to intracellular accumulation of acidic metabolites. As a result, HBO promotes intracellular acidification of both tumor cells and CSCs, triggering efficient doxorubicin release and the potent copper-mediated chemical dynamic effect of subsequently administered dual-acid-responsive HHD-Cu NPs. The combination of HBO with HHD-Cu NPs not only eliminates tumor cells but also inhibits CSCs, altogether leading to potent tumor inhibition. This study explores a new function of clinical-widely used HBO and establishes a novel combination therapy for treating CSCs abundant hypoxic solid tumors.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
STAR Protocols
·
2024
·
IF 1.3
Yuanyan Wei,Shuting Geng,Qihang Chen,Jiayue Chen,Zhijun Fan,Yi Li,Yu Si,Yuerong Yang,Ziwei Liang,Jianhai Jiang
Summary CD133 is widely used as a marker to isolate cancer stem cells (CSCs). However, the structural ambiguity of N-glycan of CD133 limits its application in the isolation of CSCs. Here, we present a protocol to sort CSCs from tumor samples by combining CD133 with α-1,2-high-mannose type glycan chains. We describe steps for purifying and biotinylating cyanovirin-N (CVN) proteins and sorting tumor cells and CD133 + α-1,2-Man + (α-1,2-linked mannose + ) cells to provide more specific markers for CSCs. For complete details on the use and execution of this protocol, please refer to Wei et al. 1
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-18
·
IF 15.7
Li Wen,Shi Zhiyuan,Jing Huaqing,Dou Yunsheng,Liu Xinyi,Zhang Mengyao,Qiu Zitong,Heger Zbynek,Li Nan
Dysregulation of extracellular matrix (ECM) homeostasis plays a pivotal role in the accelerated degradation of cartilage, presenting a notable challenge for effective osteoarthritis (OA) treatment and cartilage regeneration. In this study, we introduced an injectable hydrogel based on streamlined-zinc oxide (ZnO), which is responsive to matrix metallopeptidase (MMP), for the delivery of miR-17-5p. This approach aimed to address cartilage damage by regulating ECM homeostasis. The ZnO/miR-17-5p composite functions by releasing zinc ions to attract native bone marrow mesenchymal stem cells, thereby fostering ECM synthesis through the proliferation of new chondrocytes. Concurrently, sustained delivery of miR-17-5p targets enzymes responsible for matrix degradation, thereby mitigating the catabolic process. Notably, the unique structure of the streamlined ZnO nanoparticles is distinct from their conventional spherical counterparts, which not only optimizes the rheological and mechanical properties of the hydrogels, but also enhances the efficiency of miR-17-5p transfection. Our male rat model demonstrated that the combination of streamlined ZnO, MMP-responsive hydrogels, and miRNA-based therapy effectively managed the equilibrium between catabolism and anabolism within the ECM, presenting a fresh perspective in the realm of OA treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）