Small Structures
·
2024
·
IF 13.9
Shenghui Kang,Xiaoyu Wu,Hang Qi,Kai Yang,Ruoyu Feng,Wenlan Guo,Chen Sun,Xuexin Duan,Yanyan Wang
Development of a micromodel that recapitulates multiple mechanical properties to mimic the complex mechanical microenvironment is crucial for cell-based research. Herein, a microsystem combining structure of hydrogel matrix and acoustic streaming (AS) to mimic the cellular microenvironment is proposed, which can realize multiplex cellular mechanical cues, including matrix stiffness, fluid shear stress (FSS) generated by AS, and matrix roughness. The results demonstrate that the cell spreading area enlarges with the increase of matrix stiffness, and cell spreading is encouraged by integrin β1 cluster to polymerize actin when combines the hydrogel matrix with FSS. In addition, FSS has the influence on the roughness of the hydrogel, which further affects the cell morphology and mechanical properties, inducing mesenchymal stem cells (MSCs) differentiation into astrocytes rapidly. Meanwhile, cell migration is also enhanced by FSS stimulation, particularly, undifferentiated cells at 22 kPa hydrogel have the fastest migration speed, and change the movement model from contact inhibition to contact stimulation migration. Especially, matrix roughness and stiffness dominantly control of cell spreading and differentiation, whereas FSS affects cell migration. In conclusion, the microsystem in this work shows superior performance in regulating the spreading, differentiation, and migration of MSCs, which provides a new tool for cell-microenvironment study.
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DOI
高影响因子
Biomaterials Science
·
2025
·
IF 5.7
Yanting Li,Mengdan Ning,Haoping Long,Jiayi Zuo,Jinqiu Liang,Ting Yuan,Feng Cao,Yong Yin,Feng Jiang
To overcome therapy resistance driven by breast cancer stem cells (BCSCs) and systemic toxicity of conventional chemotherapy, we engineered a multistimuli-responsive nanoprodrug (DT/PAC@AI NPs) implementing a "chemodifferentiation-cancer stem cells inhibition" strategy. This system co-delivers irinotecan (IRI), all-trans retinoic acid (ATRA), and CPUL119 via: (1) a hypoxia-responsive prodrug (PAC: PEG₂ₖ-Azo-CPUL119), and (2) a pH/esterase-responsive conjugate (AI: ATRA-IRI). The targeted NPs (90-130 nm), modified with DSPE-PEG₂ₖ-Try for LAT1mediated uptake, demonstrated tumor microenvironment-triggered release: rapid PAC release under hypoxia and enhanced AI release at pH 5.0/esterase. In vitro, DT/PAC@AI NPs showed 20% higher cellular uptake and potent cytotoxicity against MDA-MB-231 cells (IC₅₀ = 4.77 ± 0.32 µM vs. free drugs: IRI 23.17, CPUL119 9.27, ATRA >50 µM), inducing 3.7-fold more apoptosis (32.6% vs. 8.7%). Critically, they reduced CD44⁺/CD24⁻ BCSCs by 13.7% and inhibited tumor sphere formation by 87.6%. In vivo, they achieved optimal tumor suppression and BCSC elimination in xenografts with negligible systemic toxicity. This nanoprodrug platform offers straightforward synthesis, high drug loading, and potent dual-action efficacy against bulk tumor cells and BCSCs, presenting a promising advanced breast cancer therapy.
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PubMed
高影响因子
ACS Applied Bio Materials
·
2022
·
IF 0
Daisy M. Ramos,Sama Abdulmalik,Michael R. Arul,Naseem Sardashti,Yeshavanth Kumar Banasavadi-Siddegowda,Syam P. Nukavarapu,Hicham Drissi,Sangamesh G. Kumbar
Approximately half of annual musculoskeletal injuries in the US involve tendon tears. The naturally hypocellular and hypovascular tendon environment makes tendons injury-prone and heal slowly. Tendon tissue engineering strategies often use biomimetic scaffolds combined with bioactive factors and/or cells to enhance healing. FDA-approved growth factors to promote tendon healing are lacking, which highlights the need for safe and effective bioactive factors. Our previous work evaluated insulin as a bioactive factor and identified an optimal dose to promote in vitro mesenchymal stem cell survival, division, and tenogenesis. The present work evaluates the ability of insulin-functionalized electrospun nanofiber matrices with or without mesenchymal stem cells to enhance tendon repair in a rat Achilles injury model. Electrospun nanofiber matrices were functionalized with insulin, cultured with or without mesenchymal stem cells, and sutured to transected Achilles tendons in rats. We analyzed rat tendons 4 and 8 weeks after surgery for the tendon morphology, collagen production, and mechanical properties. Bioactive insulin-functionalized fiber matrices with mesenchymal stem cells resulted in significantly increased collagen I and III at 4 and 8 weeks postsurgery. Additionally, these matrices supported highly aligned collagen fibrils in the regenerated tendon tissue at 8 weeks. However, treatment- and control-regenerated tissues had similar tensile properties at 8 weeks, which were less than that of the native Achilles tendon. Our preliminary results establish the benefits of insulin-functionalized fiber matrices in promoting higher levels of collagen synthesis and alignment needed for functional recovery of tendon repair.
研究领域:
再生医学
·
组织工程
·
生物材料科学
✓ 已验证
DOI
PubMed
BIOMATERIALS
·
2017
·
IF 8.402
Dianyu Dong,Tong Hao,Changyong Wang,Ying Zhang,Zhihui Qin,Boguang Yang,Wancai Fang,Lei Ye,Fanglian Yao,Junjie Li
Brown adipose derived stem cells (BADSCs) have become a promising stem cell treatment candidate for myocardial infarction because of their efficiently spontaneous differentiation capacity towards cardiomyocytes . The lack of existing cell passage protocols motivates us to develop a neotype 3D cell expansion technique for BADSCs. In this study, “clickable” zwitterionic starch based hydrogels are developed using methacrylate modified sulfobetaine derived starch with dithiol-functionalized poly (ethylene glycol) as crosslinker via the “thiol-ene” Michael addition reaction . Moreover, CGRGDS peptide is immobilized into the hydrogel via a similar “clickable” approach. Their Young's moduli range from 22.28 to 74.81 kPa depending on the concentration of precursor solutions . Excellent anti-fouling property is also presented owing to the introduction of zwitterionic moieties. BADSCs are homogeneously encapsulated in the hydrogels and then routinely cultured for 10 days. Results suggest a capacious cell proliferation and the extent increases with either the decrease of mechanical strength or the introduction of CGRGDS. More excitingly, the cell “stemness” is well maintained during this period and the expanded cells released from the hydrogels well keep the efficiently spontaneous cardiomyogenic differentiation capacity. Therefore, it is suggested that zwitterionic starch based hydrogel is able for the expansion and “stemness ” maintenance of BADSCs.
研究领域:
生物材料学
·
再生医学
·
细胞生物学
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高影响因子
ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Pengfei Xia,Kunxi Zhang,Yan Gong,Guifei Li,Shifeng Yan,Jingbo Yin
Microgels, with large surface area per volume, show great advantages in adipose tissue engineering due to their injectability and similarity with natural extracellular matrix. However, to date, no studies have tried applying microgels to adipose tissue regeneration. Herein, based on double-bonded poly(l-glutamic acid)-g-2-hydroxyethyl methacrylate (PLGA-g-HEMA) and maleic anhydride-modified chitosan (MCS), an open porous microgel with high hydrophilicity and great injectability is successfully prepared (microgels diameters of 200–300 μm, pore diameter of 38 μm, and porosity of 88.3%). The storage modulus of 30 mg/mL of the microgel dispersions is 2000 Pa, which is similar to that of the native adipose tissue. The spheroidal stem cell shape and extensive cell–cell connections can be formed in the present microgels to promote adipogenic differentiation and realize adipose tissue regeneration. After injection in vitro, the microgels can maintain high stem cell viability up to 14 days. The extensive Oil red O staining is observed after adipogenic induction for 14 days. After 12 weeks postimplantation, adipose tissues can be regenerated well. Blood vessels are formed in the neogenerated tissues. The degradation rate of microgels roughly matches with the adipose tissue formation rate. The study offers an applicable microgel system to boost the adipose tissue regeneration.
研究领域:
生物材料学
·
再生医学
·
组织工程学
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2020
·
IF 7.182
Jin Wang,Lehao Zhou,Qihao Sun,Haibo Cai,Wen-Song Tan
The proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) needed to be promoted for their use in stem cell-based therapy for large bone defects. This study aimed to prepare porous 2a-2 g scaffolds with antioxidant activity to reduce intracellular reactive oxygen species (ROS), which resulted in promoting the proliferation and osteogenic differentiation of MSCs. A series of novel chemically modified 2a-2 g scaffolds were fabricated by an acid-soluble/alkali-insoluble method. Besides, these 2a-2 g scaffolds had good biocompatibility, physicochemical properties and the ability to promote osteogenic differentiation of human adipose-derived stem cells ( h ADSCs). However, the proliferation ability of h ADSCs on 2a-2f scaffolds was weakened. Interestingly, 2 g scaffold had a positive effect on h ADSCs proliferation. These results indicated that the reduction of intracellular ROS was not conducive to h ADSCs proliferation but beneficial to h ADSCs osteogenic differentiation. Taken together, these significant results highlighted potential therapeutic benefit of 2 g scaffold in large bone defects.
研究领域:
生物材料
·
干细胞研究
·
组织工程
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-18
·
IF 10.2
Zhou Heng,Jing Shuili,Xiong Wei,Zhu Yangzhi,Duan Xingxiang,Li Ruohan,Peng Youjian,Kumeria Tushar,He Yan,Ye Qingsong
Spinal cord injury (SCI) is accompanied by loss of Zn2+, which is an important cause of glutamate excitotoxicity and death of local neurons as well as transplanted stem cells. Dental pulp stem cells (DPSCs) have the potential for neural differentiation and play an immunomodulatory role in the microenvironment, making them an ideal cell source for the repair of central nerve injury, including SCI. The zeolitic imidazolate framework 8 (ZIF-8) is usually used as a drug and gene delivery carrier, which can release Zn2+ sustainedly in acidic environment. However, the roles of ZIF-8 on neural differentiation of DPSCs and the effect of combined treatment on SCI have not been explored. ZIF-8-introduced DPSCs were loaded into gelatin methacryloyl (GelMA) hydrogel and in situ injected into the injured site of SCI rats. Under the effect of ZIF-8, axon number and axon length of DPSCs-differentiated neuro-like cells were significantly increased. In addition, ZIF-8 protected transplanted DPSCs from apoptosis in the damaged microenvironment. ZIF-8 promotes neural differentiation and angiogenesis of DPSCs by activating the Mitogen-activated protein kinase (MAPK) signaling pathway, which is a promising transport nanomaterial for nerve repair.
研究领域:
神经科学
·
干细胞生物学
·
材料科学
·
再生医学
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DOI
PubMed
高影响因子
MACROMOLECULAR RAPID COMMUNICATIONS
·
2020
·Vol. 41
·期 24
·2000102
·
IF 4.886
Yanan Liu,Ying Qiu,Shilei Ni,Xuewei Zhang,Hongchen Sun,Wenlong Song,Xiangwei Li
Dental pulp engineering possesses a promising perspective to replacing lost pulp in the root canal and restoring its functions. Stable adhesion of dental pulp stem cells (DPSCs) on the root canal dentin wall is a key element required for reconstruction of a functional odontoblast layer in dental pulp regeneration. To address this challenge, dopamine-modified hyaluronic acid (DA-HA) is coated on dentin to obtain a stable adhesion of DPSCs. The dopamine segment provides adhesion ability to the coating, and the hyaluronic acid increases the biocompatibility. The results show that DPSCs can adhere on the DA-HA coated dentin slice better than those without coating. Simultaneously, DPSCs proliferation can be further promoted on the prepared coating. Therefore, the DA-HA coating may provide a possible way to immobilize odontoblast cell onto dentin surface for pulp regeneration.
研究领域:
口腔医学
·
组织工程
·
生物材料学
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DOI
PubMed
高影响因子
JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
·
2015
·Vol. 15
·期 4
·2605-2612
·
IF 1.556
Lei Hulong,Nan Xiang,Wang Zhiyong,Gao Lin,Xie Lisi,Zou Chao,Wan Qian,Pan Di,Beauchamp Norman,Yang Xiaoming,Matula Thomas,Qiu Bensheng
Magnetosonoporation (MSP) is a relatively safe and efficient approach for instant MR stem cell labeling. In this study, the physical and magnetic properties of different formulations of synthesized superparamagnetic iron oxide nanoparticles (SPION) were characterized. Then, a “closed”
MSP apparatus using focused ultrasound was designed and the feasibility of MSP stem cell labelling using focused ultrasound was validated by evaluating the proliferation, migration and differentiation of the magnetically labeled cells. Subsequently, MSP/SPION labeled neural stem cells (NSCs)
were transplanted into the contralateral striatum of glioma-bearing nude mice, and their migration was monitored using magnetic resonance imaging (MRI) in vivo. The results indicated that SPION-1 with the largest size (28.43±9.55 nm) had the highest T
2 relaxivity
(136.62 Fe mM−1 S−1) and the best MRI contrast effect. Without additional transfection reagents, NSCs were labeled with SPION using focused ultrasound in vitro and the safety of MSP stem cell labeling was validated with the optimized MSP technique. Finally,
confirmed by histological evaluation, pronounced signal attenuation on T
2-weighted images demonstrated the intracranial tumor tropism of NSCs could be monitored non-invasively by MRI. In conclusion, MSP cell labeling using focused ultrasound is a promising technique and the
“closed” device is feasible, convenient and safe for instant magnetic stem cell labeling and MRI cell tracking.
研究领域:
医学影像
·
纳米技术
·
干细胞研究
·
肿瘤学
·
生物医学工程
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DOI
PubMed
高影响因子
CELL PROLIFERATION
·
2021
·Vol. 55
·期 1
·e13173
·
IF 6.831
Jinping Huang,Xiao Sheng,Zhangpeng Zhuo,Danqing Xiao,Kun Wu,Gang Wan,Haiyang Chen
Objectives Adult stem cells uphold a delicate balance between quiescent and active states, which is crucial for tissue homeostasis. Whereas many signalling pathways that regulate epithelial stem cells have been reported, many regulators remain unidentified. Materials and Methods Flies were used to generate tissue-specific gene knockdown and gene knockout. qRT-PCR was used to assess the relative mRNA levels. Immunofluorescence was used to determine protein localization and expression patterns. Clonal analyses were used to observe the phenotype. RNA-seq was used to screen downstream mechanisms. Results Here, we report a member of the chloride channel family, ClC - c , which is specifically expressed in Drosophila intestinal stem/progenitor cells and regulates intestinal stem cell (ISC) proliferation under physiological conditions and upon tissue damage. Mechanistically, we found that the ISC loss induced by the depletion of ClC - c in intestinal stem/progenitor cells is due to inhibition of the EGFR signalling pathway. Conclusion Our findings reveal an ISC-specific function of ClC - c in regulating stem cell maintenance and proliferation, thereby providing new insights into the functional links among the chloride channel family, ISC proliferation and tissue homeostasis.
研究领域:
细胞生物学
·
分子生物学
·
发育生物学
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DOI
PubMed
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
·
2024
·
IF 4.5
Hairui Tian,Xingju Wang,Xiaoxiao Li,Weixiang Song,Jiaqi Mi,Kang Zou
In the orchestrated environment of the testicular niche, the equilibrium between self-renewal and differentiation of spermatogonial stem cells (SSCs) is meticulously maintained, ensuring a stable stem cell reserve and robust spermatogenesis. Within this milieu, extracellular vesicles, specifically exosomes, have emerged as critical conveyors of intercellular communication. Despite their recognized significance, the implications of testicular exosomes in modulating SSC fate remain incompletely characterized. Given the fundamental support and regulatory influence of Sertoli cells (SCs) on SSCs, we were compelled to explore the role of SC-derived exosomes (SC-EXOs) in the SSC-testicular niche. Our investigation hinged on the hypothesis that SC-EXOs, secreted by SCs from the testes of 5-day-old mice—a developmental juncture marking the onset of SSC differentiation—participate in the regulation of this process. We discovered that exposure to SC-EXOs resulted in an upsurge of PLZF, MVH, and STRA8 expression in SSC cultures, concomitant with a diminution of ID4 and GFRA1 levels. Intriguingly, obstructing exosomal communication in a SC-SSC coculture system with the exosome inhibitor GW4869 attenuated SSC differentiation, suggesting that SC-EXOs may modulate this process via paracrine signaling. Further scrutiny revealed the presence of miR-493-5p within SC-EXOs, which suppresses Gdnf mRNA in SCs to indirectly restrain SSC differentiation through the modulation of GDNF expression—an indication of autocrine regulation. Collectively, our findings illuminate the complex regulatory schema by which SC-EXOs affect SSC differentiation, offering novel perspectives and laying the groundwork for future preclinical and clinical investigations.
研究领域:
生殖生物学
·
干细胞生物学
·
分子生物学
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DOI
PubMed
高影响因子
Artificial Cells Nanomedicine and Biotechnology
·
2018
·
IF 3.026
Yang Xia,Huimin Chen,Feimin Zhang,Lin Wang,Bo Chen,Mark A. Reynolds,Junqing Ma,Abraham Schneider,Ning Gu,Hockin H. K. Xu
Literature search revealed no systematic report on iron oxide nanoparticle-incorporating calcium phosphate cement scaffolds (IONP-CPC). The objectives of this study were to: (1) use γFe2O3 nanoparticles (γIONPs) and αFe2O3 nanoparticles (αIONPs) to develop novel IONP-CPC scaffolds, and (2) investigate human dental pulp stem cells (hDPSCs) seeding on IONP-CPC for bone tissue engineering for the first time. IONP-CPC scaffolds were fabricated. Physiochemical properties of IONP-CPC scaffolds were characterized. hDPSC seeding on scaffolds, cell proliferation, osteogenic differentiation and bone matrix mineral synthesis by cells were measured. Our data demonstrated that the osteogenic differentiation of hDPSCs was markedly enhanced via IONP incorporation into CPC. Substantial increases (about three folds) in ALP activity and osteogenic gene expressions were achieved over those without IONPs. Bone matrix mineral synthesis by the cells was increased by two- to three folds over that without IONPs. The enhanced cellular osteogenesis was attributed to: (1) the surface nanotopography of IONP-CPC scaffold, and (2) the cell internalization of IONPs released from IONP-CPC scaffold. Our results demonstrate that the novel CPC functionalized with IONPs is promising to promote osteoinduction and bone regeneration. In conclusion, it is highly promising to incorporate γIONPs and αIONPs into CPC scaffold for bone tissue engineering, yielding substantially better stem cell attachment, spreading and osteogenic differentiation, and much greater bone mineral synthesis by the seeded cells. Therefore, novel CPC scaffolds containing γIONPs and αIONPs are promising for dental, craniofacial and orthopaedic applications to substantially enhance bone regeneration.
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PubMed
高影响因子
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