Stem Cell Research & Therapy
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2024
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IF 7.1
Xinyuan Bi,Bin Ma,Wei Liu,Wei-Qiang Gao,Jian Ye,Hanyu Rao
Background Mesenchymal stem cells (MSCs) are widely applied in the treatment of various clinical diseases and in the field of medical aesthetics. However, MSCs exhibit greater heterogeneity limited stability, and more complex molecular and mechanistic characteristics compared to conventional drugs, making rapid and precise monitoring more challenging. Methods Surface-enhanced Raman spectroscopy (SERS) is an ultrasensitive, tractable and low-cost fingerprinting technique capable of identifying a wide range of molecules related to biological processes. Here, we employed SERS for reproducible quantification of ultralow concentrations of molecules and utilized spectral sets, termed SERSomes, for robust and comprehensive intracellular multi-metabolite profiling. Results We revealed that with increasing passage number, there is a gradual decline in cell expansion efficiency, accompanied by significant changes in intracellular amino acids, purines, and pyrimidines. By integrating these metabolic features detected by SERS with transcriptomic data, we established a correlation between SERS signals and biological changes, as well as differentially expressed genes. Conclusion In this study, we explore the application of SERS technique to provide robust metabolic characteristics of MSCs across different passages and donors. These results demonstrate the effectiveness of SERSome in reflecting biological characteristics. Due to its sensitivity, adaptability, low cost, and feasibility for miniaturized instrumentation throughout pretreatment, measurement, and analysis, the label-free SERSome technique is suitable for monitoring MSC expansion and offers significant advantages for large-scale MSC manufacturing. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-024-04109-0.
研究领域:
生物医学
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分子生物学
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分析化学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Subramani Kandhasamy,Baofang Wu,Jiayin Wang,Xiaojing Zhang,Gao Hongzhi,Da-Peng Yang,Yiming Zeng
Hydrogels incorporating natural biopolymer and adhesive substances have extensively been used to develop bioactive drugs and to design cells encapsulating sturdy structure for biomedical applications. However, the conjugation of the adhesive in most hydrogels is insufficient to maintain long-lasting biocompatibility inadequate to accelerate internal organ tissue repair in the essential native cellular microenvironment. The current work elaborates the synthesis of charged choline-catechol ionic liquid (BIL) adhesive and a hydrogel with an electronegative atom rich polyphenol (PU)-laden gelatinmethacryloyl (GelMA) to improve the structural bioactivities for in vivo tracheal repair by inducing swift crosslinking along with durable mechanical and tissue adhesive properties. It was observed that Bioactive BIL and PU exhibited potent antioxidant (IC 50 % of 7.91 μg/mL and 24.55 μg/mL) and antibacterial activity against E. coli , P. aeruginosa and S. aureus . The novel integration of photocurable GelMA-BIL-PU revealed outstanding mechanical strength, biodegradability and sustained drug release. The in vitro study showed exceptional cell migration and proliferation in HBECs, while in vivo investigation of the GelMA-BIL-PU hydrogel on a rat's tracheal model revealed remarkable tracheal reconstruction, concurrently reducing tissue inflammation. Furthermore, the optimized GelMA-BIL-PU injectable adhesive bioink blend demonstrated superior MSCs migration and proliferation, which could be a strong candidate for developing stem cell-rich biomaterials to address multiple organ defects.
研究领域:
生物医学工程
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组织工程
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干细胞生物学
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材料科学
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药剂学
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ACS Applied Materials & Interfaces
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2024
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IF 8.3
Zhe Wang,Lin Qi,Yong Huang,Zheng Liu,Ruibang Wu,Yize Zhao,Hao Li,Siyi Wang,Limin Liu,Li Zhang,Ganjun Feng
Leptin, a kind of adipokine, with its receptor in which the long isoform plays a crucial role in signal transduction, has been identified in intervertebral disc (IVD) tissues, especially showing an increased expression in degenerated discs. Initially identified as a metabolic sensor, leptin has recently been found able to regulate inflammation into imbalance, which favors catabolic degradative processes, thus contributing to progressive intervertebral disc degeneration (IDD). Therefore, efficiently inhibiting the leptin pathway may provide a new strategy to treat IDD. In this study, we introduced an innovative drug delivery system (DDS) that employs stem cell membranes (SCM) to encapsulate (Zeolitic imidazolate frameworks-8) ZIF-8 nanoparticles. These nanoparticles are used to transport a plasmid containing shRNA targeting the leptin receptor (LEPR), with the aim of facilitating repair in IDD. The regenerative performances of this DDS in IDD were verified through a combination of the in vitro western blot and immunofluorescence with the in vivo radiologic examination and histological staining. The DDS demonstrated excellent cell adhesion properties and gene transfection efficiency in vitro, along with impressive treatment outcomes in vivo. Both in vitro and in vivo studies revealed that the DDS effectively reduced leptin receptor expression and alleviated the inflammatory environment, thereby promoting regeneration in degenerated IVDs. We propose that the DDS represents a promising novel approach for treating IDD and may also be beneficial for other degenerative diseases linked to leptin pathway dysfunction.
研究领域:
纳米技术
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生物医学工程
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分子生物学
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再生医学
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骨科
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Bone Research
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2026
·Vol. 14
·期 1
·82
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IF 20.1
Huang Tiannan,Wu Shali,Qian Wei,Chen Ruiying,Chen Erman,Wang Meizhu,Zhang Cui,Zhou Chenhe,Yu Luyang,Wu Mengjie,Li Yi-Ping,Wu Mengrui
Exhaustion of skeletal stem and progenitor cells (SSPCs) drives age-related delays in fracture repair, yet the upstream regulators of SSPC maintenance are unclear. We identify that core-binding factor β (Cbfβ) in bone marrow Adipoq + cells (BMACs) is essential for maintaining SSPC number and function. Cbfβ deletion in BMACs (CKO) leads to SSPC depletion, including periosteal populations, and impairs bicortical fracture healing in mice. Multi-omics (RNA-seq, CUT&Tag-seq, and ATAC-seq) reveal that Cbfβ preserves chromatin accessibility at DNA repair loci, maintaining genomic stability, preventing BMAC senescence, and mitigating the senescence-associated secretory phenotype (SASP). Senolytic therapy alleviates BMAC senescence, restores SSPC populations, and improves bone repair in CKO mice. In both humans and mice, Cbfβ expression declines with aging, accompanied by increased BMAC senescence. AAV-mediated Cbfβ overexpression restores aging-related bone repair and SSPC decline. These findings reveal a novel mechanism in which Cbfβ in BMACs regulates SSPC maintenance via a senescence/SASP axis, offering a potential therapeutic strategy for age-related bone repair deficits.
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Bioactive Materials
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2026
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IF 23.6
Tiantian Xue,Jiabin Zhang,Bin Wang,Fenfang Li,Guipan Chen,Yanteng Xu,Yuechen Luo,Jiali Sun,Yeh-Hsing Lao,Jin Wang,Haixia Wang,Enguo Ju,Xi Xie,Haochen Yao,Mingqiang Li,Yu Tao
Hepatocyte-like cells (HLCs) represent a promising therapeutic approach for acute liver failure (ALF), offering an alternative to primary hepatocytes, which are in short supply. Given the viscoelastic tissue properties of the liver and the growing recognition of the mechanical cues in physiology and disease, we investigated how ALF-induced changes in the liver's mechanical microenvironment might affect HLC-based cell therapy. Here, driven by specific disease-derived mechanical cues, we designed bioinspired hydrogel microspheres with tunable liver viscoelasticity to mimic the mechanical niche of healthy versus ALF liver tissue. We show that a fast-relaxation hydrogel niche mimicking the healthy liver guides the efficient differentiation of human adipose-derived mesenchymal stem cells (hADSCs) into functional HLCs by suppressing the formation of abnormal stress fibers and pathological YAP nuclear translocation through the ROCK axis. In both the carbon tetrachloride-induced and partial hepatectomy-induced ALF mouse models, these mechanically preconditioned HLCs exhibit significant therapeutic efficacy, promoting robust liver regeneration and acting as active mechanical regulators to suppress aberrant host mechanotransduction and remodel the diseased microenvironment. This disease mechanobiology-oriented strategy provides insights into the design of viscoelastic biomaterials for regenerative medicine and demonstrates a promising approach for enhancing cell therapy outcomes in liver failure.
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ACS Applied Bio Materials
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2026
·Vol. 9
·期 15
·7069-7080
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IF 5.6
Chi Chunyu,Gao Yuantao,Chen Jiazhu,Ge Xuejun,Gao Zexing,Li Yinggang,Yan Shuang
The delayed healing of skin wounds poses significant health risks and increases medical burdens, necessitating the development of multifunctional dressings that can actively monitor and promote the healing process. In this study, a multifunctional CeO 2 /PCL nanofibrous scaffold integrating real-time pH sensing, enhanced stem cell adhesion, and antioxidant functions was developed. A series of composite scaffolds with tunable CeO 2 nanoparticle loadings (7.1–31.6 wt %) were fabricated via a facile one-step electrospinning technique. Notably, the CeO 2 /PCL-13.3 wt % scaffold achieved an optimal balance of tensile strength (1.927 MPa) and elongation at break (70%), fully satisfying clinical wound dressing requirements. Phenol red loading enabled naked-eye pH monitoring (4.0–10.0) via metal−phenolic coordination. Comprehensive evaluations demonstrated that the composite scaffolds exhibited significant antibacterial activity, potent reactive oxygen species scavenging capability, and excellent biocompatibility. The scaffolds maintained over 80% human umbilical cord mesenchymal stem cells viability within 72 h and significantly promoted stem cell migration in wound healing assays. This integrated platform unifies visual diagnostics and therapeutic functions for advanced wound management.
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ACS Sensors
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2026
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IF 10.9
Hai Shi,Lu Liu,Ying Shen,Yunlong Xiao,Renwu Mu,Suzhen Zhai,Bin Zhang,Xiaoyan Yang,Chunlin Zhang
Leukemia stem cell (LSC) phenotyping offers significant potential to enhance minimal residual disease (MRD) monitoring in acute myeloid leukemia (AML), improving therapeutic evaluation and relapse prediction. However, current approaches lack the sufficient sensitivity and specificity to reliably detect rare chemotherapy-resistant LSCs (crLSCs) or identify stem-like phenotypic states, limiting clinical translation. Here, we develop DISCERN (Dual-Aptamer-Initiated Sensing Circuit via Engineered Nanozyme), a colorimetric platform for ultrasensitive LSC phenotyping. DISCERN employs a dual-aptamer system targeting colocalized surface markers (CD33 and CD123) for high-specificity recognition. Its exceptional sensitivity (limit of detection <10 cells/mL) is achieved by a localized catalytic cascade: target-binding initiates on-site rolling circle amplification (RCA), which in turn templates the assembly of PCN-222(Fe) nanozymes that generate amplified colorimetric signals. We demonstrate that DISCERN can track phenotypic plasticity in leukemia cells and identify stem-like subsets in leukemia xenograft models. This cost-effective and robust platform provides a promising tool for AML risk stratification, relapse prediction, and precision therapy.
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ADVANCED FUNCTIONAL MATERIALS
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2026
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IF 19.9
Haoyang Ding,Jiaxiang Li,Zhen Chen,Xiangchuan Xu,Lili Hao,Lingyun Sun,Zhongwei Gu,Hongli Mao
As a critical stage in chronic liver disease, liver fibrosis can progress to irreversible damage without timely intervention. Stem cell therapy offers significant therapeutic potential owing to its potent regenerative and immunomodulatory properties. However, its clinical application is challenged by low cell survival, poor targeting, and inadequate paracrine regulation. Here, we present a magnetic hydrogel patch laden with human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) to enhance their antifibrotic efficacy via synergistic magneto-mechanical stimulation. The patch is fabricated through thiol-ene “click” chemistry using multi-thiol-functionalized magnetic nanoparticles as crosslinkers. Molecular dynamics simulations reveal the regulatory mechanism of nanoparticle concentration on the crosslinking topology of the hydrogel network, thereby identifying the optimal formulation with favorable mechanical properties and magnetic responsiveness. Under magneto-mechanical stimulation, the resulting patch significantly enhances the secretion of key antifibrotic factors from hUC-MSCs by activating the PI3K/Akt/mTOR signaling pathway. Moreover, in vitro and in vivo results demonstrate that, under magnetic stimulation, the hUC-MSC-laden magnetic patch significantly inhibits hepatic stellate cell activation, promotes anti-inflammatory macrophage polarization, reduces collagen deposition, and ameliorates the inflammatory microenvironment, thereby effectively reversing liver fibrosis. This study offers a versatile stem cell-based platform for spatiotemporally controlled therapy of liver fibrosis and potentially other fibrotic diseases.
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Journal of Materials Chemistry B
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2026
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IF 6.2
Shengke Zhu,Wei Li,Kangan Wang,Bin Hu,Shenggang Huang,Jiahao Yang,Peng Fan,Shige Wang,Yu Sun,Chunping Zhu
Wound repair is a coordinated and sequential biological process involving multiple cells and phases, with inflammation, vascularization, re-epithelialization, collagen deposition, and remodeling being critical stages. Mesenchymal stem cells, capable of sensing the wound microenvironment and secreting cytokines to regulate the repair process, have garnered significant attention in wound repair. This study developed a self-healing polysaccharide-based hydrogel system using two widely sourced polysaccharides. The main components of the hydrogel are oxidized dextran (OD) and carboxymethyl chitosan (CMCS). This hydrogel features a simple preparation process and favorable biocompatibility, serving as a carrier for cell culture to enable three-dimensional (3D) cultivation of adipose-derived mesenchymal stem cells (ADSCs). Experiments on full-thickness skin defect repair in nude mice demonstrated that the ADSC-loaded polysaccharide hydrogel (OC-ADSCs) significantly promoted wound closure, collagen deposition, epidermal regeneration, as well as angiogenesis and vessel maturation. The OC-ADSC hydrogel can function as a novel cell delivery system, synergistically promoting wound healing and tissue regeneration by modulating the wound microenvironment, showing potential for clinical translation.
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Frontiers in Cell and Developmental Biology
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2025
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IF 4.3
Jinhua Yan,Chenxi Feng,Hanmei Zhang,Ting Luo,Haiyang Chen,Haiou Chen
Introduction Intestinal stem cells (ISCs) possess the ability to self-renew and differentiate, which is essential for maintaining intestinal tissue homeostasis. However, their functionality significantly declines with age, leading to diminished tissue regeneration and an increased risk of age-associated diseases. Methods This study investigates the effects of Dapagliflozin (DAPA), a novel insulin sensitizer and SGLT2 inhibitor, on aging ISCs using the Drosophila melanogaster model. Our findings demonstrate that DAPA can inhibit the MAPK signaling pathway, as confirmed by network pharmacology analysis and molecular docking experiments. Results DAPA ameliorates ISC aging, improves intestinal function (including enhanced fecal excretion, restored intestinal barrier integrity and acid-base balance), and enhances healthspan. These results highlight the potential of DAPA as an anti-aging therapeutic agent. Discussion This study provides new evidence for the application of DAPA as an anti-aging treatment.
研究领域:
细胞生物学
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分子生物学
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药物学
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ACS Applied Materials & Interfaces
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2025
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IF 8.2
RongBai Ju,Xinghui Gao,Chi Zhang,Weibing Tang,Siyuan Zhang,Fangjun Huo,Ning Song,Wei Tang,Weidong Tian,Min He
Host immune rejection has long been recognized as a major contributor to the poor survival rates of exogenous stem cells (ESCs). In this study, we present a simple and versatile strategy to protect ESCs from host immune system insults by developing a protective “armor.” This armor was designed using tannic acid (TA), leveraging its strong affinity for biomacromolecules and its anti-inflammatory properties. Prior to implantation, the armor can be readily applied to the surface of individual ESCs, cell aggregates, cell sheets, or cell-laden hydrogel systems by simply immersing them in a TA solution for several seconds, without additional processing steps. The TA-based armor effectively modulates the acute inflammatory response during the initial days postimplantation by scavenging reactive oxygen species (ROS), thereby creating an ESCs-friendly immune microenvironment. This was evidenced by reduction in the infiltration of pro-inflammatory immune cells and the secretion of pro-inflammatory cytokines. Consequently, the survival of engrafted ESCs was significantly enhanced, with preserved stemness and immunomodulatory functions. The regenerative potential of ESCs was further demonstrated in a rat periodontal defect model. These findings provide a novel approach for enhancing the regenerative performance of ESCs and offer a straightforward and versatile strategy to shield ESCs from host immune rejection.
研究领域:
生物医学工程
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免疫学
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再生医学
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ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
·
2025
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IF 4.2
Xiaofeng Chen,Yucheng Zhu,Minghan Li,Chunyan Zhou,Fang Luo,Zechang Li,Jiangyu Zhang,Liguo Xing,Wei Liu
Acetamiprid (ACE), a Neonicotinoid insecticides (NEOs), is highly selective for insect nicotinic acetylcholine receptors (nAChRs). However, increasing evidence of hazards was reported in mammals. We investigated the effects of ACE on both global DNA methylation and epigenetic change, transcriptomic dysregulation, and neural differentiation. ACE decreased AluYb8 methylation levels in human mesenchymal stem cells. TET2 expression was enhanced suggesting that it was involved in the active DNA demethylation caused by ACE. Global DNA methylation pattern identified 87 significant differentially methylated positions (DMPs) and transcriptomic analysis identified 385 differentially expressed genes (DEGs). Pathways related to the psychiatric system, including Alzheimer's disease and TGF-β, were significantly enriched. ACE inhibited the expression of neurogenesis marker MAP2 and SNCA, which was repressed by TETs inhibitor Bobcat339. Our results suggested that exposure to ACE disturbed DNA methylation, and resulted in the impaired neural differentiation revealed by abnormal expression of neuronal and PD-related marker protein.
研究领域:
毒理学
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表观遗传学
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神经科学
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环境健康
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干细胞生物学
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