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Stem Cells International · 2024 ·Vol. 2024 ·期 1 ·7419270 · IF 3.8

Comparative Analysis of the Therapeutic Effects of MSCs From Umbilical Cord, Bone Marrow, and Adipose Tissue and Investigating the Impact of Oxidized RNA on Radiation-Induced Lung Injury

Rui Zhai,Fumin Tai,Kexin Ding,Xin Tan,Hujie Li,Zhengyue Cao,Changhui Ge,Xiaofei Zheng,Hanjiang Fu

Radiation-induced lung injury (RILI) is frequently observed in patients undergoing radiotherapy for thoracic malignancies, constituting a significant complication that hampers the effectiveness and utilization of tumor treatments. Ionizing radiation exerts both direct and indirect detrimental effects on cellular macromolecules, including DNA, RNA and proteins, but the impact of oxidized RNA in RILI remains inadequately explored. Mesenchymal stem cells (MSCs) can repair injured tissues, and the reparative potential and molecular mechanism of MSCs in treating RILI remains incompletely understood. This study aimed to investigate the therapeutic effects and mechanisms of action of three distinct sources of MSCs, including human umbilical cord mesenchymal stem cells (UCMSCs), bone marrow mesenchymal stem cells (BMSCs), and adipose-derived stem cells (ADSCs), in thoracically irradiated mice. Comparative analysis revealed that all three types of MSCs exhibited the ability to mitigate radiation-induced inflammatory infiltration, alveolar hemorrhage, and alveolar wall thickening in the lung tissue of the mice. MSCs also attenuated RILI by decreasing inflammatory factors, upregulating anti-inflammatory factor expression, and reducing collagen accumulation. Immunohistochemical results showed that all three MSCs reduced radiation-induced cell apoptosis and promoted the regeneration of lung tissue cells. The analysis of malondialdehyde (MDA) and 8-hydroyguanosine (8-OHG) content indicated that MSCs possess reparative properties against radiation-induced oxidative damage in lung tissue. The study provides evidence that UCMSCs are a more appropriate therapeutic option for RILI compared to BMSCs and ADSCs. Additionally, MSCs effectively reduce the accumulation of oxidized RNA in RILI, thereby, presenting a unique avenue for investigating the underlying mechanism of MSC-based treatment for RILI.

CAS / MDL: 54827-17-7
研究领域: 肿瘤学 · 干细胞生物学 · 放射生物学 · 肺科学 · 分子生物学
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JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION · 2018 · IF 1.911

The growth and pluripotency of mesenchymal stem cell on the biodegradable polyurethane synthesized with ferric catalyst

Qianqian Wei,Jiachang Jin,Xinyuan Wang,Qijun Shen,Mi Zhou,Shizhong Bu,Yabin Zhu

Polyurethane (PU) is a class of polymers that have been applied for tissue-engineering scaffolds. Cross-linked poly(ester urethane) (CPU), synthesized with ferric catalyst in our laboratory, was modified by silk fibroin (SF) grafting using our aminolysis and glutaradehyde crosslinking method. The physical and chemical properties of the materials were investigated by scanning electron microscope (SEM), atomic force microscope (AFM) and tensile tester. The results showed that SF grafted CPU possessed good strain and strength (4.29 ± 0.18 MPa/382.38 ± 0.71%). Its surface chemistry and roughness were fine to well support the growth of bone marrow mesenchymal stem cells (BMSC). The cells were verified to maintain the pluripotency after they were cultured in vitro for 2 weeks, which supplied us a good technology to keep cell’s stemness but proliferate cell’s number. These results are valuable for us to further study esophageal tissue engineering with BMSC and polyurethane materials as the components.

CAS / MDL: 14024-18-1
研究领域: 材料科学 · 生物材料 · 组织工程 · 干细胞生物学
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Advanced Biology · 2021 ·Vol. 6 ·期 2 ·2101050 · IF 0

Mesenchymal Stem Cell Exosomes and Cancer: Controversies and Prospects

Sirine Yassine,Nada Alaaeddine

Mesenchymal stem cells (MSCs) have displayed a novel therapeutic strategy for a wide range of diseases and conditions. Their secretome and exosome-based paracrine activity are considered as the main processes harboring their diverse therapeutic properties. Several investigations have examined the effects of MSC-derived exosomes on cancer growth, yet, controversial results have always emerged. Although MSC-derived exosomes are able to rigorously enforce the repression of cancer proliferation and progression, it is shown that MSCs exosomal activity displays numerous protumorigenic effects. This discrepancy over the dual effects of MSCs on cancer growth may be mediated by many factors including experimental design, stem cells origins, culture conditions, in addition to cancer-MSCs cross-talks. Despite the controversial effects of MSCs on carcinogenesis, scientists are able to overcome a number of obstacles by modifying MSCs to deliver antioncogenic miRNAs, anticancer drugs, and oncolytic viruses into tumor sites. This review discusses the controversial effects of MSC-derived exosomes on tumorigenesis, investigates the main causes that underlie this discrepancy, summarizes the pattern of engineered-MSCs, and finally highlights how future studies should advance the research in the field of MSCs-based cancer therapies in order to accelerate the transition from preclinical studies to clinical practice.

研究领域: 细胞生物学 · 肿瘤学 · 再生医学
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Bioactive Materials · 2024 · IF 18

Protocol for engineering bone organoids from mesenchymal stem cells

Jian Wang,Dongyang Zhou,Ruiyang Li,Shihao Sheng,Guangfeng Li,Yue Sun,Peng Wang,Yulin Mo,Han Liu,Xiao Chen,Zhen Geng,Qin Zhang,Yingying Jing,Long Bai,Ke Xu,Jiacan Su

Bone organoids are emerging as powerful tools for studying bone development and related diseases. However, the simplified design of current methods somewhat limits their application potential, as these methods produce single-tissue organoids that fail to replicate the bone microarchitecture or achieve effective mineralization. To address this issue, we propose a three-dimensional (3D) construction strategy for generating mineralized bone structures using bone marrow-derived mesenchymal stem cells (BMSCs). By mixing BMSCs with hydrogel to create a bone matrix-mimicking bioink and employing projection-based light-curing 3D printing technology, we constructed 3D-printed structures, which were then implanted subcutaneously into nude mice, away from the native bone microenvironment. Even without external stimulation, these implants spontaneously formed mineralized bone domains. With long-term culture, these structures gradually matured into fully differentiated bone tissue, completing both mineralization and vascularization. This in vivo bone organoid model offers a novel platform for studying bone development, exploring congenital diseases, testing drugs, and developing therapeutic applications.

研究领域: 组织工程 · 再生医学 · 干细胞生物学 · 骨骼发育 · 药物测试
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ACS Nano · 2023 · IF 17.1

Magnetic Microcarriers with Accurate Localization and Proliferation of Mesenchymal Stem Cell for Cartilage Defects Repairing

Mengjiao Ma,Faxing Zou,Bahatibieke Abudureheman,Feng Han,Guoli Xu,YaJie Xie,Kun Qiao,Jiang Peng,Yueping Guan,Haoye Meng,Yudong Zheng

Magnetic biomaterials are widely used in the field of tissue engineering because of their functions such as drug delivery and targeted therapy. In this study, a magnetically responsive composite microcarrier was prepared through in situ polymerization of dopamine with Fe3O4 (MS) to form a complex. The magnetic composite microcarriers are paramagnetic and have certain magnetic responsiveness, suitable pore size porosity for cell growth, and good blood compatibility and biocompatibility. The bone marrow mesenchyml stem cells (BMSCs) were cultured on magnetic composite microcarriers, and a static magnetic field (SMF) was applied. The results showed that BMSCs adhered to the microcarriers proliferated under the action of horizontal and vertical forces. Magnetic composite microcarriers loaded with BMSCs were implanted into the SD rat model of cartilage defect, and a magnet was added to the operative side. After 12 weeks, cartilage regeneration was observed. The results of gross observation and histological immunostaining 1 month, 2 months, and 3 mounths after operation showed that the magnetic composite microcarriers of loaded cells promoted the early maturation of cartilage and collagen secretion, and the effect of cartilage repair was significantly better than that of the control group. Gait analysis showed that implanting magnetic composite microcarriers loaded with stem cells can reduce postoperative pain and promote limb recovery in SD rats. In conclusion, this study suggests that magnetic composite microcarriers are promising tissue-engineered scaffolds for cartilage regeneration and repair.

研究领域: 组织工程 · 生物医学工程 · 再生医学
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Advanced Healthcare Materials · 2023 ·Vol. 12 ·期 17 ·2202904 · IF 10

Cell Membranes from Tumor-Tropic MSCs Screened by a Microfluidic Chip for Drug Nanoparticles Encapsulation and Cancer Targeted Therapy

Yizuo Song,Xin Shou,Bo Sheng,Jie Mei,Keqing Shi,Luoran Shang,Xueqiong Zhu

Nanoparticles (NPs)-based drug carriers are effective in reducing systemic toxicity and drug resistance for chemotherapy, and an emerging trend focuses on integrating cell membranes with nanomedicines for tumor targeting. Mesenchymal stem cells (MSCs) are promising candidates due to their unique tropism toward cancer cells, yet the tumor-tropic abilities can differ for MSCs sourced from different tissues. Here, a multichannel microfluidic chip to screen different sourced MSCs with the greatest tropism toward cervical cancer cells is developed. Based on this, the cell membranes from the chorionic plate-derived MSC are isolated and membrane-camouflaged platinum prodrug composite NPs for cervical cancer treatment are prepared. Results demonstrate that the composite NPs can effectively target tumor sites and have a therapeutic effect both in vitro and in vivo. It is believed that the present microfluidic platform is a powerful tool for cell screening and tumor-on-a-chip studies, and the derived nanodelivery system represents the great value of cell membrane-camouflaged nanomedicine for targeted cancer therapy.

研究领域: 生物医学工程 · 纳米技术 · 癌症研究 · 干细胞生物学 · 药学 · 微流控技术
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Cell Journal · 2021 · IF 2.479

Mir-106b Cluster Regulates Primordial Germ Cells Differentiation from Human Mesenchymal Stem Cells

Sadaf Mahboudi,Kazem Parivar,Zohreh Mazaheri,Shiva Irani

Objective Numerous evidence indicates that microRNAs (miRNAs) are critical regulators in the spermatogenesisprocess. The aim of this study was to investigate Mir-106b cluster regulates primordial germ cells (PGCs) differentiationfrom human mesenchymal stem cells (MSCs). Materials and Methods In this experimental study, samples containing male adipose (n: 9 samples- age: 25-40 years)were obtained from cosmetic surgeries performed for the liposuction in Imam Khomeini Hospital. The differentiationof MSCs into PGCs was accomplished by transfection of a lentivector expressing miR-106b . The transfection of miR-106b was also confirmed by the detection of a clear green fluorescent protein (GFP) signal in MSCs. MSCs weretreated with bone morphogenic factor 4 (BMP4) protein, as a putative inducer of PGCs differentiation, to induce thedifferentiation of MSCs into PGCs (positive control). After 4 days of transfection, the expression of miR-106b , STELLA,and FRAGILIS genes was evaluated by real-time polymerase chain reaction (PCR). Also, the levels of thymocytedifferentiation antigen 1 (Thy1) protein was assessed by the western blot analysis. The cell surface expression of CD90was also determined by immunocytochemistry method. The cytotoxicity of miR-106b was examined in MSCs after 24,48, and 72 hours using the MTT assay. Results MSCs treated with BMP4 or transfected by miR-106b were successfully differentiated into PGCs. The resultsof this study also showed that the expression of miR-106b was significantly increased after 48 hours from transfection.Also, we showed STELLA, FARGILIS , as well as the protein expression of Thy1, was significantly higher in MSCstransfected by lentivector expressing miR-106b in comparison with MSCs treated with BMP4 (P≤0.05). MTT assayshowed miR-106b was no toxic during 72 hours in 1 µg/ml dose, that this amount could elevated germ cells markersignificantly higher than other experimental groups (P≤0.05). Conclusion According to this findings, it appears that miR-106b plays an essential role in the differentiation of MSCsinto PGCs.

CAS / MDL: 329-98-6
研究领域: 分子生物学 · 生殖医学 · 干细胞研究
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Nano Select · 2024 · IF 0

Electrochemical Mineralization Regulates Hydroxyapatite Deposition of Silk Fibroin Nanofibers for Promoting Osteogenic Differentiation of Human Mesenchymal Stem Cells

Leihao Lu,Xiao Yang,Dulin Wang,Suting Zhong,Ying Zhang,Guanshan Zhou,Chenlin Li,Jie Wang,Mingying Yang

Scaffold and stem cells are the key elements in the procedure of bone repair. Bombyx mori silk fibroin (SF) is the proper material for bone tissue engineering due to its biocompatibility and its easy to obtain nanofiber structure. The suitable cell substrate is also an important factor because different cells have different adaptations to composite. For this case, selecting a scaffold that can promote osteogenic differentiation of various cells is crucial and meaningful. In this work, hydroxyapatite (HA) was deposited precisely onto each silk nanofiber by electrochemical mineralization (EC) to form SF/HA. SF/HA can promote the proliferation and osteogenic differentiation of both human bone marrow mesenchymal-derived stem cells (hMSCs) and human adipose-derived mesenchymal stem cells (hAMSCs). It also promot the expression of alkaline phosphatase (ALP) and osteogenic differentiation related genes. Western blot analyses show mitogen-activated protein kinase (MAPK) signal pathway is regulated by SF/HA. Therefore, the study provides a proper method to obtain a good composite SF/HA and it promotes the osteogenic differentiation of both hMSCs and hAMSCs.

研究领域: 生物材料 · 组织工程 · 干细胞分化 · 生物医学工程
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Materials Today Communications · 2025 · IF 4.5

Synthesis and characterization of photocrosslinked gelatin-silk fibroin composite microspheres for mesenchymal stem cell expansion and osteogenic differentiation

Liuxin Yang,Guanhua Jiao,Dandan Wei,Tianzhu Zhang

Microspheres have shown great potential as biomaterial substrates for culturing and expanding stem cells to meet the requirements of cell therapy. Gelatin microspheres have been widely researched in cell culture; however, the size, pore structure, and stability of these microspheres still need to be further optimized. In this study, gelatin methacrylamide (GelMA) and glycidyl-methacrylate-modified silk fibroin (SFMA) composite microspheres (denoted as GSM microspheres) were synthesized using a simple water-oil (W/O) emulsion method followed by photo-crosslinking. The swelling ratio (34 % (w/v) GelMA = 799.8 ± 67.7 %; 34 % (w/v) GSM = 643.1 ± 66.3 %) and degradation ratio (relative weights at 15 d: 34 % (w/v); GelMA = 13.3 ± 3.9 %; 34 % (w/v) GSM = 38.6 ± 6.2 %) of GSM microspheres decreased with the incorporation of SFMA. Moreover, the constructed microspheres demonstrated adjustable size distribution (from 75 to 775 µm for GM0 to 25–275 µm for GSM3), pore structure, and surface curvature. Thus, the initial cell adhesion efficiency of microspheres increased with the content of GelMA (GSM1, GSM2, and GSM3 was 39.5 %, 23.3 %, and 7.7 %, respectively), and the cell amplification achieved by microsphere-microsphere transfer demonstrates the potential for cell expansion in vitro . In addition, On the higher curvature surface of GSM3, the cells were overspread and the shape factor of the nucleus was high (0.88 ± 0.05). Alkaline phosphatase (ALP) activity, osteogenesis-related gene expression, and Alizarin Red S staining showed that the addition of SFMA could promote osteogenic differentiation of BMSCs. Thus, the composite microspheres can serve as an adjustable three-dimensional (3D) culture platform for the amplification and osteogenic differentiation of BMSCs.

研究领域: 生物材料学 · 细胞生物学 · 再生医学
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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

Single stem cell encapsulation by MnO2 doped hydrogel for robust bone regeneration

Yu Tian,Pengxia Zhang,Zhen Ma,Mengya Li,Yali Fan,Rui Guo,YanFeng Li,Yingying Zhang

Mesenchymal stem cells (MSCs) have become an important choice for regenerative medicine because of their specific differentiation ability. However, MSCs are rapidly cleared by direct injection, and living cells need to be embedded in a 3D semipermeable hydrogel matrix to prolong cell retention time to enhance therapeutic effects. Herein, MnO 2 doped alginate hydrogel was prepared for single stem cell encapsulation (SA@MSC-MnO 2 ) with maintaining biological activity. This hydrogel system could accelerate the differentiation potential of MSCs and promoted 60 % repair of bone defects within 8 weeks. Besides, the doping of MnO 2 could react with H 2 O 2 to generate H 2 O and O 2 , thus achieving the goal of reactive oxygen species (ROS) clearing and improving the bone regeneration effects. We believe that this single stem cell hydrogel encapsulation system will further promote the clinical application of stem cell therapy.

CAS / MDL: 60-00-4
研究领域: 再生医学 · 生物材料科学
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Experimental and Therapeutic Medicine · 2014 ·Vol. 7 ·期 6 ·1738-1744 · IF 0.941

Effects of methylthiouracil on the proliferation and apoptosis of rat bone marrow stromal cells

Zhong‑Lu Ye,Xiao‑Xiao Hou,Re‑Ling Chen,Jie Ding,Guo‑Hua Zheng,Ming‑Zhen Chen,Chuan Tian

The aim of the present study was to investigate the effects of methylthiouracil (MTU) on the proliferation and apoptosis of rat bone marrow stromal cells (BMSCs). Rat BMSCs were isolated, cultured in vitro and treated with various concentrations of MTU. Cell growth curves were determined using the Cell Counting Kit‑8 method and the effect of MTU on BMSCs in a logarithmic growth phase was observed. BMSC apoptosis following MTU treatment was detected by flow cytometry. The experimental results demonstrated that the proliferation‑inhibition effect was gradually enhanced with increasing MTU concentrations and the extension of treatment time. Statistically significant differences were observed between the treatment and the control groups (P<0.05). In addition, the BMSC apoptosis rate gradually increased with increasing drug concentrations and treatment time extension; statistically significant differences were observed between the treatment and the control groups (P<0.05). Therefore, the results of the present study demonstrated that MTU inhibited the proliferation of BMSCs and promoted apoptosis, indicating the cytotoxic effects of MTU on BMSCs.

CAS / MDL: 91795-77-6 56-04-2
研究领域: 细胞生物学 · 药理学
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ACS Applied Materials & Interfaces · 2019 · IF 8.456

Graphene/Si-Promoted Osteogenic Differentiation of BMSCs through Light Illumination

Xiaojun Long,Xiaozhao Wang,Lili Yao,Suya Lin,Jiamin Zhang,Wenjian Weng,Kui Cheng,Huiming Wang,Jun Lin

Graphene (Gr) presents promising applications in regulating the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Light illumination is regarded as a spatiotemporally controllable, easily applicable, and noninvasive mean to modulate material responses. Herein, Gr-transferred silicon (Gr/Si) with a Schottky junction is utilized to evaluate the visible-light-promoted osteogenic differentiation of BMSCs. Under light illumination, light-induced charges, owing to the formation of the Schottky junction at the interface of Gr and Si, accumulated on the surface and then changed the surface potential of Gr/Si. The Schottky junction and surface potential at the interface of Gr and Si was measured by photovoltaic test and scanning Kelvin probe microscopy. Alkaline phosphatase (ALP) activity and quantitative real-time polymerase chain reaction (PCR) measurement showed that such variations of surface improved the osteogenic differentiation of BMSCs, and the activation of the voltage-gated calcium channels through surface potential and accumulation of cytosolic Ca2+ could be the reason. Moreover, X-ray photoelectron spectroscopy characterization showed that surface charge could also affect BMSCs differentiation through the promotion or inhibition of the adsorption of osteogenic growth factors. Such light-promoted osteogenic differentiation of BMSCs on Gr/Si may have huge potential for biomedical materials or devices for bone regeneration application.

研究领域: 生物材料学 · 医学工程
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