Journal of Tissue Engineering and Regenerative Medicine
·
2017
·Vol. 12
·期 3
·e1609
·
IF 3.989
Yunlong Zhang,Xin Niu,Xin Dong,Yang Wang,Haiyan Li
In cell therapy, tissue regeneration ability of stem cells relies on the paracrine effects between stem cells and recipient cells. Our recent studies demonstrated that, in tissue engineering, bioactive silicates could stimulate paracrine effects between stem cells and recipient cells, which enhanced tissue generation. Therefore, we proposed that, in cell therapy, it may be an effective method to improve tissue regeneration ability of stem cells through activating the paracrine effects between stem cells and recipient cells with bioactive silicates. As urine-derived stem cells (USCs) have been injected for wound healing and bioglass (BG) have shown bioactivity for various types of stem cells, in this study, we activated USCs with effective BG ionic products. Then the conditioned medium of BG-activated USCs were used to culture endothelial cells and fibroblasts as well as co-cultures of endothelial cells and fibroblasts. Results showed that growth factor expression in BG-activated USCs was upregulated. In addition, paracrine effects between USCs and recipient cells in wound healing were stimulated, which resulted in enhanced capillary-like network formation of endothelial cells and matrix protein production as well as myofibroblast differentiation of fibroblasts. Finally, the BG-activated USCs were applied on full-thickness excisional wounds. Results confirmed that BG-activated USCs had better wound healing ability through improving angiogenesis and collagen deposition in wound sites as compared with USCs without any treatment. Taken together, BG can be used to promote wound healing ability of USCs by enhancing paracrine effects between USCs and recipient cells.
研究领域:
细胞生物学
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再生医学
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生物材料学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 2
·1240
·
IF 5.6
Hang Yao,Xiaohui Yuan,Zhonglian Wu,Sumin Park,Wang Zhang,Hui Chong,Liwei Lin,Yuanzhe Piao
A gelatin/sodium alginate-based hydrogel microsphere has been fabricated after reaction condition optimization. Macrophages (RAW246.7) and adipose mesenchymal stem cells (ADSC) have been subsequently encapsulated in the microsphere in order to construct a 3D paracrine system for wound healing treatment. The synthesized microsphere displayed neglectable cytotoxicity toward both encapsulated cells until 10 days of incubation, indicating promising biocompatibility of the microsphere. A qRT-PCR and ELISA experiment revealed positive regulation of cytokines (Arg-1, IL-6, IL-8, IL-10, bFGF, HGF, VEGF, TLR-1, and CXCL13) expression regarding macrophage phenotype transformation and anti-inflammatory performance both inside the microsphere and in the microenvironment of established in vitro inflammatory model. Additionally, positive tendency of cytokine expression benefit wound healing was more pronounced in a fabricated 3D paracrine system than that of a 2D paracrine system. Furthermore, the 3D paracrine system exhibited more efficiently in the wound healing rate compared to the 2D paracrine system in an in vitro model. These results suggested the current paracrine system could be potentially used as a robust wound healing dressing.Keywords:wound healing dressing;paracrine system;biocompatibility;3D cell culture;natural polymer
研究领域:
生物学
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医学工程
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再生医学
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DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2024
·
IF 4.7
Chaoying Jin,Ruolin Zhao,Weihang Hu,Xiaolong Wu,Li Zhou,Letian Shan,Huiling Wu
Background Pressure ulcer is common in the bedridden elderly with high mortality and lack of effective treatment. In this study, human-adipose-derived-stem-cells-hyaluronic acid gel (hADSCs-HA gel) was developed and applied topically to treat pressure ulcers, of which efficacy and paracrine mechanisms were investigated through in vivo and in vitro experiments.Methods Pressure ulcers were established on the backs of C57BL/6 mice and treated topically with hADSCs-HA gel, hADSCs, hyaluronic acid, and normal saline respectively. The rate of wound closure was observed continuously during the following 14 days and the wound samples were obtained for Western blot, histopathology, immunohistochemistry, and proteomic analysis. Human dermal fibroblasts (HDFs) and human venous endothelial cells (HUVECs) under normal or hypoxic conditions were treated with conditioned medium of human ADSCs (ADSC-CM), then CCK-8, scratch test, tube formation, and Western blot were conducted to evaluate the paracrine effects of hADSCs and to explore the underlying mechanism.Results The in vivo data demonstrated that hADSCs-HA gel significantly accelerated the healing of pressure ulcers by enhancing collagen expression, angiogenesis, and skin proliferation. The in vitro data revealed that hADSCs strengthened the proliferation and wound healing capabilities of HDFs and HUVECs, meanwhile promoted collagen secretion and tube formation through paracrine mode. ADSC-CM was also proved to exert protective effects on hypoxic HDFs and HUVECs. Besides, the results of proteomic analysis and Western blot elucidated that lipid metabolism and PPARβ/δ pathway mediated the healing effect of hADSCs-HA gel on pressure ulcers.Conclusion Our research showed that topical application of hADSCs-HA gel played an important role in dermal regeneration and angiogenesis. Therefore, hADSCs-HA gel exhibited the potential as a novel stem-cell-based therapeutic strategy of treating pressure ulcers in clinical practices.
研究领域:
生物医学工程
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干细胞生物学
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组织工程
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伤口愈合
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产品关联
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
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干细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
Cell Death & Disease
·
2018
·Vol. 9
·期 3
·1-15
·
IF 5.638
Ding Yue,Liang Xiaoting,Zhang Yuelin,Yi Li,Shum Ho Cheung,Chen Qiulan,Chan Barbara P.,Fan Huimin,Liu Zhongmin,Tergaonkar Vinay,Qi Zhongquan,Tse Hung-fat,Lian Qizhou
Immunomodulatory activity of mesenchymal stem cells (MSCs) is largely mediated by paracrine factors. Our previous studies showed that activation of nuclear factor-kappa B (NF-κB) regulates cytokine/growth factor secretion by MSCs. This study aimed to elucidate the role of Rap1 (repressor/activator protein), a novel modulator involved in the NF-κB pathway, in regulating the immunomodulatory potency of MSCs in acute allograft rejection of heart transplantation. The immunosuppressive potency of wild-type MSCs (WT-MSCs) or Rap1-deficient MSCs (Rap1 −/− -MSCs) was examined in mice with acute allograft rejection following heart transplantation. With a combination of immunosuppressant rapamycin at a dose of 1 mg/kg/d, WT-MSCs notably prolonged the survival of the transplanted heart compared with Rap1 −/− -MSCs. Rap1 −/− -MSCs displayed a marked insensitivity to inhibit the mixed lymphocyte reaction (MLR) due to impaired cytokine production and a significantly reduced activity of NF-κB signaling in vitro . Finally, transplantation of encapsulated WT-MSCs greatly prolonged the survival of the heart allograft compared with encapsulated Rap1 −/− -MSCs. Our results indicate that Rap1 is essential to maintain the immunomodulatory function of MSCs. Deletion of Rap1 results in impaired immunomodulatory function of MSCs.
研究领域:
免疫学
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干细胞研究
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移植医学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
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2024
·
IF 4.3
Jinze Li,Jiali Zhang,Hao Ye,Qixuan Wang,Yanran Ouyang,Yuxi Luo,Yihong Gong
Introduction: Mesenchymal stem cells (MSCs) possess a high degree of self-renewal capacity and in vitro multi-lineage differentiation potential. Decellularized materials have garnered considerable attention due to their elevated biocompatibility, reduced immunogenicity, excellent biodegradability, and the ability to partially mimic the in vivo microenvironment conducive to cell growth. To address the issue of mesenchymal stem cells losing their stem cell characteristics during two-dimensional (2D) cultivation, this study established three-dimensional cell carriers modified with lung decellularized extracellular matrix and assessed its impact on the life activities of mesenchymal stem cells. Methods: This study employed PET as a substrate material, grafting with polydopamine (PDA), and constructing a decellularized extracellular matrix (dECM) coating on its surface, thus creating the PET/PDA/dECM three-dimensional (3D) composite carrier. Subsequently, material characterization of the cellular carriers was conducted, followed by co-culturing with human umbilical cord mesenchymal stem cells in vitro , aiming to investigate the material’s impact on the proliferation and paracrine activity of mesenchymal stem cells. Results and Discussion: Material characterization demonstrated successful grafting of PDA and dECM materials, and it had complete hydrophilicity, high porosity, and excellent mechanical properties. The material was rich in various ECM proteins (collagen I, collagen IV , laminin, fibronectin, elastin), indicating good biocompatibility. In long-term in vitro cultivation (14 days) experiments, the PET/PDA/dECM three-dimensional composite carrier significantly enhanced adhesion and proliferation of human umbilical cord-derived mesenchymal stem cells (HUCMSCs), with a proliferation rate 1.9 times higher than that of cells cultured on tissue culture polystyrene (TCPS) at day 14. Furthermore, it effectively maintained the stem cell characteristics, expressing specific antigens for HUCMSCs. Through qPCR, Western blot, and ELISA experiments, the composite carrier markedly promoted the expression and secretion of key cell factors in HUCMSCs. These results demonstrate that the PET/PDA/dECM composite carrier holds great potential for scaling up MSCs’ long-term in vitro cultivation and the production of paracrine factors.
研究领域:
组织工程
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干细胞生物学
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生物材料
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细胞治疗
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Xiaoyun Peng,Wenjing Song,Zijian Yan,Wei Zhai,Li Ren
Despite their clinical success, stem cells (SCs) in the treatment of osteoarthritis (OA) are limited by lower retention efficiency and restricted paracrine function. The development of effective SCs culture and delivery systems to maintain or promote SCs paracrine function is urgently needed. In this study, we focused on gelatin microcarriers with different sizes as SCs culture scaffold for OA therapy. The effect of culturing adipose-derived stem cells (ADSCs) on different size microcarriers (180 μm and 320 μm) to promote paracrine function was evaluated. The secretome of ADSCs cultured on microcarriers more effectively regulated macrophages and chondrocytes in a direction favorable to OA healing compared to culture plates. In particular, microcarriers with ADSCs effectively reduced the coefficient of friction at the cartilage interface. Injection low-dose ADSCs without and with different size microcarriers into the knee joints in rats' OA model was achieved. Even better OA therapeutic effects were achieved by using smaller size (higher curvature) microcarriers to deliver ADSCs at low doses. Microcarrier-based cell delivery strategies offer potential solution method for OA therapy.
研究领域:
干细胞生物学
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骨科
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再生医学
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组织工程
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产品关联
DOI
PubMed
高影响因子
Materials Today Advances
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2025
·
IF 8
Lina Huang,Chao Lin,Hanyi Hua,Zehao Chen,Yong Xu,Kezhen Zhou,Xiaoming Liu,Yifan Li,Jiangming Yu,Xiaojian Ye,Xiaoxiao Li,Shuai Jiang
In osteoporotic bone defects, bone marrow mesenchymal stem cells (BMSCs) play a pivotal role in tissue regeneration by orchestrating the local microenvironment through both differentiation and paracrine signaling. However, persistent pathological stimuli such as oxidative stress significantly impair their functionality, while limited cell survival and homing efficiency at the defect site remain major obstacles hindering therapeutic efficacy. To overcome these issues, we designed a stem cell delivery system using microfluidic techniques, in which microspheres were modified with resveratrol. This system leveraged a sustained-release liposomal formulation of resveratrol to enhance the antioxidant resilience of BMSCs. Simultaneously, the platform created a three-dimensional porous microenvironment using pH-responsive microspheres, which supported the maintenance of paracrine activity and promoted osteogenic differentiation of transplanted cells, thereby accelerating bone regeneration. In vitro experiments demonstrated that this system significantly enhanced mineralized nodule formation, accompanied by marked upregulation of osteogenesis-related genes and proteins including RUNX2, COL-1, and SP7. Furthermore, BMSCs exhibited increased secretion of key paracrine factors such as VEGFA, thereby improving proangiogenic support to endothelial cells. In vivo study, we employed an osteoporotic rat model with femoral bone defects, micro-CT imaging and multimodal histological analyses confirmed that the proposed platform markedly facilitated new bone formation and structural tissue reconstruction. Collectively, this study proposes a synergistic strategy for osteoporotic bone repair, providing a new approach to cell therapy design.
研究领域:
再生医学
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组织工程
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干细胞生物学
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骨科学
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生物材料学
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药物递送系统
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产品关联
DOI
高影响因子
Advanced Science
·
2023
·Vol. 10
·期 17
·2206814
·
IF 15.1
Renwang Sheng,Jia Liu,Wei Zhang,Yifan Luo,Zhixuan Chen,Jiayu Chi,Qingyun Mo,Mingyue Wang,Yuzhi Sun,Chuanquan Liu,Yanan Zhang,Yue Zhu,Baian Kuang,Chunguang Yan,Haoyang Liu,Ludvig J. Backman,Jialin Chen
Stiffness is an important physical property of biomaterials that determines stem cell fate. Guiding stem cell differentiation via stiffness modulation has been considered in tissue engineering. However, the mechanism by which material stiffness regulates stem cell differentiation into the tendon lineage remains controversial. Increasing evidence demonstrates that immune cells interact with implanted biomaterials and regulate stem cell behaviors via paracrine signaling; however, the role of this mechanism in tendon differentiation is not clear. In this study, polydimethylsiloxane (PDMS) substrates with different stiffnesses are developed, and the tenogenic differentiation of mesenchymal stem cells (MSCs) exposed to different stiffnesses and macrophage paracrine signals is investigated. The results reveal that lower stiffnesses facilitates tenogenic differentiation of MSCs, while macrophage paracrine signals at these stiffnesses suppress the differentiation. When exposed to these two stimuli, MSCs still exhibit enhanced tendon differentiation, which is further elucidated by global proteomic analysis. Following subcutaneous implantation in rats for 2 weeks, soft biomaterial induces only low inflammation and promotes tendon-like tissue formation. In conclusion, the study demonstrates that soft, rather than stiff, material has a greater potential to guide tenogenic differentiation of stem cells, which provides comprehensive evidence for optimized bioactive scaffold design in tendon tissue engineering.
研究领域:
生物材料
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组织工程
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细胞生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2022
·
IF 4.145
Yanling Zhang,Zhiyun Du,Dan Li,Zhuo Wan,Tianyi Zheng,Xuehui Zhang,Yingjie Yu,Xiaoping Yang,Qing Cai
Due to the inflammatory responses associated with defect occurrence and materials implantation, immunoregulation has emerged as a promising strategy to enhance bone regeneration . It has been widely reported that a material could facilitate osteogenesis if it can guide macrophages to anti-inflammatory M2 phenotype, vice versa, a substrate will influence macrophage phenotype if it is osteoinductive. However, few studies have looked into the intercellular crosstalking directly. Herein, the compound catalpol was selected for its multiple functions to study the interactions between bone marrow mesenchymal stromal cells (BMSCs) and macrophages. This iridoid glucoside exhibits excellent anti-inflammatory and osteoinductive activities. The effects of catalpol on mediating M1/M2 polarization of macrophages, inhibiting osteoclast differentiation , promoting osteogenesis and angiogenesis were systematically investigated to correlate the biological responses of BMSCs and macrophages. To extend its in vivo application, the catalpol was then loaded onto an electrospun polylactide/gelatin composite fibrous mesh and subcutaneously implanted to evaluate the local inflammation and ectopic osteogenesis. The results revealed that the functions of catalpol displayed in modulating cellular behaviors are via cell paracrine to strengthen intercellular crosstalking, hence demonstrating that catalpol itself could serve as a promising bioactive stimulator for bone tissue engineering.
研究领域:
组织工程
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生物材料
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免疫学
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细胞生物学
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再生医学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Jianmei Chen,Chun Pan,Ya Gao,Qihong Chen,Xueying An,Zongguang Liu
Cell-based therapies offer tremendous potential for skin flap regeneration. However, the hostile microenvironment of the injured tissue adversely affects the longevity and paracrine effects of the implanted cells, severely reducing their therapeutic effectiveness. Here, an injectable hydrogel (nGk) with reactive oxygen species (ROS) scavenging capability, which can amplify the cell viability and functions of encapsulated mesenchymal stem cells (MSCs), is employed to promote skin flap repair. nGk is formulated by dispersing manganese dioxide nanoparticles (MnO2 NPs) in a gelatin/κ-carrageenan hydrogel, which exhibits satisfactory injectable properties and undergoes a sol–gel phase transition at around 40 °C, leading to the formation of a solid gel at physiological temperature. MnO2 NPs enhance the mechanical properties of the hydrogel and give it the ability to scavenge ROS, thus providing a cell-protective system for MSCs. Cell culture studies show that nGk can mitigate the oxidative stress, improve cell viability, and boost stem cell paracrine function to promote angiogenesis. Furthermore, MSC-loaded nGk (nGk@MSCs) can improve the survival of skin flaps by promoting angiogenesis, reducing inflammatory reactions, and attenuating necrosis, providing an effective approach for tissue regeneration. Collectively, injectable nGk has substantial potential to enhance the therapeutic benefits of MSCs, making it a valuable delivery system for cell-based therapies.
研究领域:
组织工程
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干细胞治疗
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再生医学
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生物医用材料
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伤口愈合
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产品关联
DOI
PubMed
高影响因子
Science of Advanced Materials
·
2024
·Vol. 16
·期 11
·1150-1156
·
IF 0.9
Yang Shiqing,Lian Yunfei,Song Ge,Ni Huiyan,Jia Beidi,Qian Xinyu,He Guanxu,Ullah Aftab,Qi Xueyong
Background: The uterine endometrium plays a important role in the processes of fertilization and embryogenesis, with its impairment or dysfunction leading to pathologies such as intrauterine adhesions, miscarriage, and infertility. In addressing endometrial damage, the application
of stem cell has attracted considerable attention. To promote the paracrine capabilities of mesenchymal stem cells (MSCs), this study employed pro-inflammatory cytokines (Tumor Necrosis Factor-α and Interferon-γ, TNF-α and IFN-γ, IT) along with 3D culture techniques
on pretreated MSCs (3D-IT-MSCs). We focused on evaluating the therapeutic potential of 3D-IT-MSCs and elucidating the mechanisms involved in endometrial repair. Method: Pretreated MSCs were co-cultured with human umbilical vein endothelial cells (HUVECs) or drug-induced endometrial
stromal cells (ESCs) to observe the promoting effect on biological function. Results: The findings demonstrated that 3D-IT-MSCs exhibit markedly elevated paracrine molecule expression and secretion compared to conventional MSCs. Additionally, treatment with 3D-IT-MSCs significantly
promoted the proliferation and migration of HUVECs and ESCs, resulting in increased HUVECs angiogenesis and inhibition of mifepristone-induced ESCs apoptosis. Conclusion: Our findings demonstrated that the combined approach of applying pro-inflammatory cytokines and 3D culture techniques
on pretreated MSCs holds substantial promise as a therapeutic strategy for repairing endometrial injuries.
研究领域:
生殖生物学
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干细胞治疗
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组织工程
·
再生医学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）