[Objectives] To investigate the effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) on the NOD-like receptor protein 3 (NLRP3)/cysteinyl aspartate specific proteinase (Caspase-1) pathway within the cerebr...[Objectives] To investigate the effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) on the NOD-like receptor protein 3 (NLRP3)/cysteinyl aspartate specific proteinase (Caspase-1) pathway within the cerebral cortex of a mouse model of Alzheimer s disease (AD).[Methods] Twelve 6-month-old female APP/PS1 mice were randomly assigned to two groups: the model group (MOD, n =6) and the hUC-MSCs treatment group (MSC, n =6). Six 6-month-old C57BL/6N mice were utilized as a control group (CON, n =6). All mice underwent caudal vein injections of hUC-MSCs. Following a 4-week treatment, the mice from each group were euthanized. The expression levels of NLRP3, Caspase-1 protein, and mRNA in the cerebral cortex of each group were assessed using Western blotting and real-time fluorescence quantitative PCR assays.[Results] The results of immunoblotting showed that the expression levels of NLRP3 and Caspase-1 proteins in the MOD group were significantly higher than those observed in the CON group. Furthermore, the expression levels of NLRP3 and Caspase-1 proteins in the MSC group were found to be lower than those in the MOD group. Additionally, the findings from real-time fluorescence quantitative PCR assay demonstrated that the mRNA levels of NLRP3 and Caspase-1 in the MOD group were elevated compared to the CON group. Conversely, the mRNA levels of NLRP3 and Caspase-1 in the MSC group were reduced in comparison to the MOD group.[Conclusions] hUC-MSCs have the capacity to modulate the expression of the NLRP3/Caspase-1 pathway within the cerebral cortex of APP/PS1 mice. This modulation may be associated with the neuroinflammatory processes mediated by hUC-MSCs in the brains of APP/PS1 mice.展开更多
Lung cancer is one of the most common malignancies with the highest morbidity and mortality in the world,and the existing treatment methods often face challenges such as toxic side effects and drug resistance.Human um...Lung cancer is one of the most common malignancies with the highest morbidity and mortality in the world,and the existing treatment methods often face challenges such as toxic side effects and drug resistance.Human umbilical cord mesenchymal stem cells(hUC-MSCs)have become a promising new strategy in cancer treatment due to their unique biological characteristics(e.g.,self-renewal,multi-differentiation and immune regulation).This paper reviews the mechanism of hUC-MSCs in regulating the proliferation,apoptosis,invasion and metastasis of lung cancer cells and tumor microenvironment,and discusses the dual effect of HUC-MSCs in promoting or inhibiting cancer.In addition,this paper also discusses the engineering transformation strategy of hUC-MSCs as gene and drug carriers,which provides a new research idea and theoretical basis for the development of hUC-MSC-based targeted therapy for lung cancer.展开更多
Purpose:To investigate the regulatory role of nerve injury-induced protein 1(NINJ1)in the anti-inflammatory function of human umbilical cord mesenchymal stem cells(hUC-MSCs)co-stimulated by interferon-gamma(IFN-γ)and...Purpose:To investigate the regulatory role of nerve injury-induced protein 1(NINJ1)in the anti-inflammatory function of human umbilical cord mesenchymal stem cells(hUC-MSCs)co-stimulated by interferon-gamma(IFN-γ)and tumor necrosis factor-alpha(TNF-α).Methods:hUC-MSCs were expanded in vitro using standard protocols,with stem cell characteristics confirmed by flow cytometry and multilineage differentiation assays.The immunomodulatory properties and cellular activity of cytokine-co-pretreated hUC-MSCs were systematically evaluated via quantitative reverse transcription RT-qPCR,lymphocyte proliferation suppression assays,and Cell Counting Kit-8 viability tests.Transcriptome sequencing,Western blotting and small interfering RNA interference were integrated to analyze the regulatory mechanisms of NINJ1 expression.Functional roles of NINJ1 in pretreated hUC-MSCs were elucidated through gene silencing combined with lactate dehydrogenase release assays,Annexin V/Propidium Iodide apoptosis analysis,macrophage co-culture models,and cytokine Enzyme-Linked Immunosorbent Assay.Therapeutic efficacy was validated in a cecal ligation and puncture-induced septic mouse model:80 mice were randomly allocated into 4 experimental groups(n=20/group):sham group(laparotomy without cecal ligation);phosphate-buffered salinetreated group(cecal ligation and puncture(CLP)+0.1 mL phosphate-buffered saline);hUC-MSCs(small interfering RNA(siRNA)-interferon-gamma and tumor necrosis factor-alpha co-stimulation(IT))-treated group(CLP+hUC-MSCs transfected with scrambled siRNA);and hUC-MSCs(siNINJ1-IT)-treated group(CLP+hUC-MSCs with NINJ1-targeting siRNA).Results:hUC-MSCs demonstrated compliance with International Society for Cellular Therapy criteria,confirming their stem cell identity.IFN-γ/TNF-αco-pretreatment enhanced the immunosuppressive capacity of hUC-MSCs,accompanied by the reduction of cellular viability,while concurrently upregulating pro-inflammatory cytokines such as interleukin-6 and interleukin-1β.This co-stimulation significantly elevated NINJ1 expression in hUC-MSCs,whereas genetic silencing of NINJ1 effectively suppressed pro-inflammatory cytokine production and attenuated damage-associated molecular patterns release through inhibition of programmed plasma membrane rupture.Furthermore,the NINJ1 interference potentiated the ability of cytokine-pretreated hUC-MSCs to suppress LPS-induced pro-inflammatory responses in RAW264.7 macrophages.In cecal ligation and puncture-induced sepsis model,NINJ1-silenced hUC-MSCs exhibited enhanced therapeutic efficacy,manifested by reduced systemic inflammation and multi-organ damage.Conclusion:Our findings shed new light on the immunomodulatory functions of cytokine-primed MSCs,offering groundbreaking insights for developing MSC-based therapies against inflammatory diseases via interfering the expression of NINJ1.展开更多
【目的】观察电针百会、风府、双侧肾俞穴联合人脐带间充质干细胞(hUC-MSCs)移植对缺血性脑损伤大鼠的脑保护作用及机制。【方法】将40只SD大鼠随机分为正常组、模型组、移植组、联合组,每组10只。除正常组,其他各组大鼠建立脑缺血再灌...【目的】观察电针百会、风府、双侧肾俞穴联合人脐带间充质干细胞(hUC-MSCs)移植对缺血性脑损伤大鼠的脑保护作用及机制。【方法】将40只SD大鼠随机分为正常组、模型组、移植组、联合组,每组10只。除正常组,其他各组大鼠建立脑缺血再灌注损伤模型。在造模结束24 h后,移植组大鼠给予0.5 m L 2×10^(6)个hUC-MSCs细胞悬液一次性尾静脉植入,联合组在移植组治疗基础上,给予电针百会穴、风府穴、双侧肾俞穴,每次30 min,每日1次,连续针刺3周。治疗结束后,苏木素-伊红(HE)染色法观察海马组织病理形态,脱氧核糖核苷酸末端转移酶介导的缺口末端标记(TUNEL)法观察脑组织细胞凋亡情况,免疫荧光法检测脑组织腺苷A2A受体(ADORA2A)表达,免疫组织化学法检测脑组织糖原合酶激酶3β(GSK-3β)、β-连环蛋白(β-catenin)表达,Western Blot法检测脑组织跨膜蛋白闭锁蛋白(Occludin)、胞质附着蛋白(ZO-1)表达。【结果】与正常组比较,模型组脑组织细胞凋亡率升高,脑组织ADORA2A阳性表达率及GSK-3β蛋白表达水平升高,Occludin、ZO-1、β-catenin蛋白表达水平降低(P<0.05),HE染色结果显示,模型组海马组织结构明显异常;与模型组比较,移植组和联合组大鼠脑组织细胞凋亡率降低,脑组织ADORA2A阳性表达率及GSK-3β蛋白表达水平降低,Occludin、ZO-1、β-catenin蛋白表达水平升高(P<0.05),海马组织病理程度明显减轻;与移植组比较,联合组脑组织细胞凋亡率降低,脑组织ADORA2A阳性表达率及GSK-3β蛋白表达水平降低,Occludin、ZO-1、β-catenin蛋白表达水平升高(P<0.05)。【结论】电针百会、风府、双侧肾俞穴联合hUC-MSCs可改善缺血性脑损伤大鼠血脑屏障,抑制脑组织ADORA2A、GSK-3β表达,提高β-catenin表达,抑制脑组织细胞凋亡,起到脑保护作用,且作用效果优于单纯hUC-MSCs移植。展开更多
Objective To investigate the effect of electronspun PLGA/HAp/Zein scaffolds on the repair of cartilage defects. Methods The PLGA/HAp/Zein composite scaffolds were fabricated by electrospinning method. The physiochemic...Objective To investigate the effect of electronspun PLGA/HAp/Zein scaffolds on the repair of cartilage defects. Methods The PLGA/HAp/Zein composite scaffolds were fabricated by electrospinning method. The physiochemical properties and biocompatibility of the scaffolds were separately characterized by scanning electron microscope （SEM）, transmission electron microscope （TEM）, and fourier transform infrared spectroscopy （FTIR）, human umbilical cord mesenchymal stem cells （hUC-MSCs） culture and animal experiments. Results The prepared PLGA/HAp/Zein scaffolds showed fibrous structure with homogenous distribution, hUC-MSCs could attach to and grow well on PLGA/HAp/Zein scaffolds, and there was no significant difference between cell proliferation on scaffolds and that without scaffolds （P〉0.05）. The PLGA/HAp/Zein scaffolds possessed excellent ability to promote in vivo cartilage formation. Moreover, there was a large amount of immature chondrocytes and matrix with cartilage lacuna on PLGA/HAp/Zein scaffolds. Conclusion The data suggest that the PLGA/HAp/Zein scaffolds possess good biocompatibility, which are anticipated to be potentially applied in cartilage tissue engineering and reconstruction.展开更多
基金Supported by Major Project of Fundamental Research Funds for the Central Universities of Chengde Medical University(KY202217)Construction of Chengde Biomedical Industry Research Institute(202205B086).
文摘[Objectives] To investigate the effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) on the NOD-like receptor protein 3 (NLRP3)/cysteinyl aspartate specific proteinase (Caspase-1) pathway within the cerebral cortex of a mouse model of Alzheimer s disease (AD).[Methods] Twelve 6-month-old female APP/PS1 mice were randomly assigned to two groups: the model group (MOD, n =6) and the hUC-MSCs treatment group (MSC, n =6). Six 6-month-old C57BL/6N mice were utilized as a control group (CON, n =6). All mice underwent caudal vein injections of hUC-MSCs. Following a 4-week treatment, the mice from each group were euthanized. The expression levels of NLRP3, Caspase-1 protein, and mRNA in the cerebral cortex of each group were assessed using Western blotting and real-time fluorescence quantitative PCR assays.[Results] The results of immunoblotting showed that the expression levels of NLRP3 and Caspase-1 proteins in the MOD group were significantly higher than those observed in the CON group. Furthermore, the expression levels of NLRP3 and Caspase-1 proteins in the MSC group were found to be lower than those in the MOD group. Additionally, the findings from real-time fluorescence quantitative PCR assay demonstrated that the mRNA levels of NLRP3 and Caspase-1 in the MOD group were elevated compared to the CON group. Conversely, the mRNA levels of NLRP3 and Caspase-1 in the MSC group were reduced in comparison to the MOD group.[Conclusions] hUC-MSCs have the capacity to modulate the expression of the NLRP3/Caspase-1 pathway within the cerebral cortex of APP/PS1 mice. This modulation may be associated with the neuroinflammatory processes mediated by hUC-MSCs in the brains of APP/PS1 mice.
基金The Project of Health and Wellness Science and Technology Plan in Baotou City(No.wsjkkj2022081).
文摘Lung cancer is one of the most common malignancies with the highest morbidity and mortality in the world,and the existing treatment methods often face challenges such as toxic side effects and drug resistance.Human umbilical cord mesenchymal stem cells(hUC-MSCs)have become a promising new strategy in cancer treatment due to their unique biological characteristics(e.g.,self-renewal,multi-differentiation and immune regulation).This paper reviews the mechanism of hUC-MSCs in regulating the proliferation,apoptosis,invasion and metastasis of lung cancer cells and tumor microenvironment,and discusses the dual effect of HUC-MSCs in promoting or inhibiting cancer.In addition,this paper also discusses the engineering transformation strategy of hUC-MSCs as gene and drug carriers,which provides a new research idea and theoretical basis for the development of hUC-MSC-based targeted therapy for lung cancer.
基金supported by the National Natural Science Foundation of China(No.82302436)Science Foundation of State Key laboratory of Trauma and Chemical Poisoning(No.2024K003).
文摘Purpose:To investigate the regulatory role of nerve injury-induced protein 1(NINJ1)in the anti-inflammatory function of human umbilical cord mesenchymal stem cells(hUC-MSCs)co-stimulated by interferon-gamma(IFN-γ)and tumor necrosis factor-alpha(TNF-α).Methods:hUC-MSCs were expanded in vitro using standard protocols,with stem cell characteristics confirmed by flow cytometry and multilineage differentiation assays.The immunomodulatory properties and cellular activity of cytokine-co-pretreated hUC-MSCs were systematically evaluated via quantitative reverse transcription RT-qPCR,lymphocyte proliferation suppression assays,and Cell Counting Kit-8 viability tests.Transcriptome sequencing,Western blotting and small interfering RNA interference were integrated to analyze the regulatory mechanisms of NINJ1 expression.Functional roles of NINJ1 in pretreated hUC-MSCs were elucidated through gene silencing combined with lactate dehydrogenase release assays,Annexin V/Propidium Iodide apoptosis analysis,macrophage co-culture models,and cytokine Enzyme-Linked Immunosorbent Assay.Therapeutic efficacy was validated in a cecal ligation and puncture-induced septic mouse model:80 mice were randomly allocated into 4 experimental groups(n=20/group):sham group(laparotomy without cecal ligation);phosphate-buffered salinetreated group(cecal ligation and puncture(CLP)+0.1 mL phosphate-buffered saline);hUC-MSCs(small interfering RNA(siRNA)-interferon-gamma and tumor necrosis factor-alpha co-stimulation(IT))-treated group(CLP+hUC-MSCs transfected with scrambled siRNA);and hUC-MSCs(siNINJ1-IT)-treated group(CLP+hUC-MSCs with NINJ1-targeting siRNA).Results:hUC-MSCs demonstrated compliance with International Society for Cellular Therapy criteria,confirming their stem cell identity.IFN-γ/TNF-αco-pretreatment enhanced the immunosuppressive capacity of hUC-MSCs,accompanied by the reduction of cellular viability,while concurrently upregulating pro-inflammatory cytokines such as interleukin-6 and interleukin-1β.This co-stimulation significantly elevated NINJ1 expression in hUC-MSCs,whereas genetic silencing of NINJ1 effectively suppressed pro-inflammatory cytokine production and attenuated damage-associated molecular patterns release through inhibition of programmed plasma membrane rupture.Furthermore,the NINJ1 interference potentiated the ability of cytokine-pretreated hUC-MSCs to suppress LPS-induced pro-inflammatory responses in RAW264.7 macrophages.In cecal ligation and puncture-induced sepsis model,NINJ1-silenced hUC-MSCs exhibited enhanced therapeutic efficacy,manifested by reduced systemic inflammation and multi-organ damage.Conclusion:Our findings shed new light on the immunomodulatory functions of cytokine-primed MSCs,offering groundbreaking insights for developing MSC-based therapies against inflammatory diseases via interfering the expression of NINJ1.
文摘【目的】观察电针百会、风府、双侧肾俞穴联合人脐带间充质干细胞(hUC-MSCs)移植对缺血性脑损伤大鼠的脑保护作用及机制。【方法】将40只SD大鼠随机分为正常组、模型组、移植组、联合组,每组10只。除正常组,其他各组大鼠建立脑缺血再灌注损伤模型。在造模结束24 h后,移植组大鼠给予0.5 m L 2×10^(6)个hUC-MSCs细胞悬液一次性尾静脉植入,联合组在移植组治疗基础上,给予电针百会穴、风府穴、双侧肾俞穴,每次30 min,每日1次,连续针刺3周。治疗结束后,苏木素-伊红(HE)染色法观察海马组织病理形态,脱氧核糖核苷酸末端转移酶介导的缺口末端标记(TUNEL)法观察脑组织细胞凋亡情况,免疫荧光法检测脑组织腺苷A2A受体(ADORA2A)表达,免疫组织化学法检测脑组织糖原合酶激酶3β(GSK-3β)、β-连环蛋白(β-catenin)表达,Western Blot法检测脑组织跨膜蛋白闭锁蛋白(Occludin)、胞质附着蛋白(ZO-1)表达。【结果】与正常组比较,模型组脑组织细胞凋亡率升高,脑组织ADORA2A阳性表达率及GSK-3β蛋白表达水平升高,Occludin、ZO-1、β-catenin蛋白表达水平降低(P<0.05),HE染色结果显示,模型组海马组织结构明显异常;与模型组比较,移植组和联合组大鼠脑组织细胞凋亡率降低,脑组织ADORA2A阳性表达率及GSK-3β蛋白表达水平降低,Occludin、ZO-1、β-catenin蛋白表达水平升高(P<0.05),海马组织病理程度明显减轻;与移植组比较,联合组脑组织细胞凋亡率降低,脑组织ADORA2A阳性表达率及GSK-3β蛋白表达水平降低,Occludin、ZO-1、β-catenin蛋白表达水平升高(P<0.05)。【结论】电针百会、风府、双侧肾俞穴联合hUC-MSCs可改善缺血性脑损伤大鼠血脑屏障,抑制脑组织ADORA2A、GSK-3β表达,提高β-catenin表达,抑制脑组织细胞凋亡,起到脑保护作用,且作用效果优于单纯hUC-MSCs移植。
基金financially supported by the National Natural Science Foundation of China,No.31070862Science and Technology Plan of Guangzhou,No.12C32071662+1 种基金Research Foundation of Guangdong Provincial Bureau of Traditional Chinese Medicine,No.2013113scientific research and cultivating Foundation of the First Clinical Medical College of Jinan University,No.2012103 and No.2013208
文摘Objective To investigate the effect of electronspun PLGA/HAp/Zein scaffolds on the repair of cartilage defects. Methods The PLGA/HAp/Zein composite scaffolds were fabricated by electrospinning method. The physiochemical properties and biocompatibility of the scaffolds were separately characterized by scanning electron microscope （SEM）, transmission electron microscope （TEM）, and fourier transform infrared spectroscopy （FTIR）, human umbilical cord mesenchymal stem cells （hUC-MSCs） culture and animal experiments. Results The prepared PLGA/HAp/Zein scaffolds showed fibrous structure with homogenous distribution, hUC-MSCs could attach to and grow well on PLGA/HAp/Zein scaffolds, and there was no significant difference between cell proliferation on scaffolds and that without scaffolds （P〉0.05）. The PLGA/HAp/Zein scaffolds possessed excellent ability to promote in vivo cartilage formation. Moreover, there was a large amount of immature chondrocytes and matrix with cartilage lacuna on PLGA/HAp/Zein scaffolds. Conclusion The data suggest that the PLGA/HAp/Zein scaffolds possess good biocompatibility, which are anticipated to be potentially applied in cartilage tissue engineering and reconstruction.
