Transplantation of bone marrow-derived MSCs improves cisplatinum-induced renal injury through paracrine mechanisms

Mesenchymal stem cells (MSCs) have been reported to preserve renal function in various models of acute kidney injury (AKI). Different routes were used to transplant MSCs but the role of cell transplantation routes in directing outcomes has been unknown. In the present study, we evaluated organ bio-distributions of transplanted MSCs, and correlated survival of transplanted cells with outcomes in mice with cisplatinum-induced AKI. We found that after intravenous administration, MSCs were largely localized in pulmonary capillaries and only a minute fraction of MSCs entered kidneys and the cells survived only transiently. Therefore, we also transplanted MSCs via intraperitoneal and renal subcapsular routes. Transplanted MSCs survived longer in peritoneal cavity and renal subcapsular space. Interestingly, when MSC transplantation was followed by cisplatinum-induced AKI, renal morphology and renal functions were better preserved, irrespective of the cell transplantation route. As transplanted MSCs did not migrate to kidneys from either peritoneal cavity or renal subcapsular space, this finding suggested that migration of cells was not required for the beneficial response. The possibility of indirect mechanisms was confirmed when administration of the conditioned medium from MSCs also protected renal tubular cells from cisplatinum-induced cytotoxicity. We identified presence of over forty regulatory cytokines in the conditioned medium obtained from MSCs. Since paracrine factors released by transplanted cells accounted for improvements, it appears that the route of cell transplantation is not critical for realizing benefits of cell therapy with MSCs in AKI. Studies of specific cytokines secreted by MSCs will help to obtain new therapeutic mechanisms for renal protection.     

Multi-modal transfection agent based on monodisperse magnetic nanoparticles for stem cell gene delivery and tracking

Directing the controlled differentiation and tracking of stem cells is essential to achieve successful stem cell therapy. In this work, we describe a multi-modal (MR/optical) transfection agent (MTA) for efficient gene delivery and cell tracking of human mesenchymal stem cells (hMSCs). The MTA was synthesized through a facile two-step approach with 1) ligand exchange of a catechol-functionalized polypeptide (CFP) and 2) chemical immobilization of fluorescence labelled cationic polymer via aminolysis reaction. Cationic polymer-immobilized MTAs with size of ∼40 nm exhibit greatly enhanced colloidal stability in aqueous solution. In addition, the MTAs were capable of binding DNA molecules for transfection. The MTA/pDNA complex showed relatively good transfection efficiency in hMSCs (compared to the commercial transfection agent, Lipofectamine) and good biocompatibility. MTA-treated hMSCs were successfully visualized after transplantation via MR and optical imaging system over 14 days. These studies highlight the challenges associated with the potential advantages of designing multi-modal nanostructured materials as tools for genetic materials delivery and cell-tracking in stem cell therapy.     

人胎肝MSCs的分离培养及其类ESCs特性的研究

目的： 建立一种简便、有效且经济的分离人胎肝间充质干细胞(hFL-MSCs)的方法,在此基础上研究hFL-MSCs的类胚胎干细胞特性。方法: 利用二步离心及羟乙基淀粉沉淀法分离hFL-MSCs,根据不同类型细胞对培养瓶的不同黏附特性,通过多次传代纯化得到hFL-MSCs;用流式细胞仪检测hFL-MSCs的细胞周期及表面标志;用免疫细胞化学及RT-PCR检测AKP、hTERT、SSEA-4和Oct-3等胚胎干细胞标志在hFL-MSCs中的表达;在不同条件下,诱导hFL-MSCs向类神经元、成肌细胞及胰岛β样细胞分化并加以鉴定。结果: 从人胎肝中分离、纯化得到MSCs,P3代hFL-MSCs有91.2%处于G0/G1期;hFL-MSCs高表达CD29和CD44,不表达造血细胞标志CD34和CD45,极低表达与GVHD相关的HLA-DR、CD80、CD86和CD106;hFL-MSCs表达Oct-4、SSEA-4、AKP和hTERT等胚胎干细胞标志;在不同诱导条件下,hFL-MSCs可分化为类神经元、肌样细胞以及胰岛β样细胞。结论: 二步离心联合羟乙基淀粉沉淀法是一种简便、高效且低成本的分离hFL-MSCs的方法;hFL-MSCs具有类胚胎干细胞的特性,体外诱导可向3个胚层来源的细胞分化,且免疫原性弱, 是组织工程和细胞治疗较为理想的种子细胞。     

Preparation and identification of multifunctional mesoporous silica nanoparticles for in vitro and in vivo dual-mode imaging,theranostics, and targeted tracking

Mesoporous silica nanoparticles (MSNs) can provide a structural foundation for a new generation of nanocarriers with a broad range of functionalities. Multifunctional MSNs can serve as all-in-one diagnostic and therapeutic tools that can be used to simultaneously visualize and treat various diseases, such as cancer. This research study is the first time that two lanthanide-based imaging systems have been combined to incorporate controlled drug release and targeted tracing into a single MSN-based nano-platform for a novel theranostic drug delivery system. Doping lanthanide ions, i.e., europium (Eu) and gadolinium (Gd) ions, into an MSN structure (EuGd-MSNs) imparts fluorescence and magnetism to the nanostructure that can be used to develop magnetic resonance imaging (MRI) and biological fluorescence tools. Current cancer research has revealed that most human cancer cells express a large number of folate receptors on their surface. Grafting folic acid (FA) onto the EuGd-MSN surface (EuGd-FA-MSNs) imparts a targeting function to the MSN because of the specificity of the binding of FA to cell surface receptors. Furthermore, grafting anticancer drugs, such as camptothecin (CPT), onto the surface of these MSNs by forming disulfide bonds (EuGd-SS-CPT-FA-MSNs) enables intracellular controlled drug release. A high concentration of intracellular glutathione cleaves the disulfide bond to release the drug and treat the disease. The results of in vitro and in vivo studies show that the functionalized MSNs can be successfully used as a platform to integrate dual-imaging, targeting, and therapeutic treatment in multifunctional diagnosis drug delivery systems.     

Inorganic photosensitizer coupled Gd-based upconversion luminescent nanocomposites for in vivo magnetic resonance imaging and near-infrared-responsive photodynamic therapy in cancers

Inorganic photosensitizer coupled Gd-based upconversion luminescent (UCL) nanocomposites have potential application for both magnetic resonance imaging (MRI) and photodynamic therapy (PDT) of cancers using the light stability and biocompatibility of TiO₂ inorganic photosensitizer. However, TiO₂ inorganic photosensitizer could only be excited by ultraviolet (UV) light, which was harmful and weakly penetrable in tissues. In this work, folic acid (FA)-targeted NaGdF₄:Yb/Tm@SiO₂@TiO₂ nanocomposites (FA-Gd-Si-Ti NPs) were constructed and synthesized for both in vivo MRI and near infrared (NIR)-responsive inorganic PDT, in which TiO₂ component could be excited by NIR light due to the UCL performance of NaGdF₄:Yb/Tm component converting NIR to UV light. The results showed the as-prepared FA-Gd-Si-Ti NPs had good biocompatibility in vitro and in vivo. Moreover, MR study indicated that FA-Gd-Si-Ti NPs were good T₁-weighted MRI contrast agents with high longitudinal relaxivity (r₁) of 4.53 mm⁻¹ s⁻¹, also in vivo MRI of nude mice showed “bright” signal in MCF-7 tumor. Under the irradiation of 980 nm laser at the power density of 0.6 W/cm² for 20 min, the viability of HeLa and MCF-7 cells incubated with FA-Gd-Si-Ti NPs could decrease from about 90 % to 35 % and 31%, respectively. Furthermore, in vivo PDT of MCF-7 tumor-bearing nude mice model showed that the inhibition ratio of tumors injected with FA-Gd-Si-Ti NPs reached up to 88.6% after 2-week treatment, compared with that of nude mice in control group. Based on the deep penetration of NIR light and the good biocompatibility of TiO₂ inorganic photosensitizer, the as-prepared FA-Gd-Si-Ti NPs could have potential applications in both MRI and NIR-responsive PDT of cancers in deep tissues.     

MSCs-FGF2基因治疗对急性肺损伤小鼠的保护作用

目的研究间充质干细胞-纤维母细胞生长因子2(MSCsFGF2)基因治疗对脂多糖诱导的急性肺损伤小鼠的保护作用。方法 40只雄性C57/B6小鼠随机分为对照组、急性肺损伤组、MSCs组、MSCs-FGF2组,每组10只。应用脂多糖建立小鼠急性肺损伤模型,观察4组小鼠肺组织病理改变、计算肺损伤评分、计算肺组织湿重与干重比值,计数支气管肺泡灌洗液(BALF)中中性粒细胞数量,实时PCR方法检测小鼠肺组织FGF2 mRNA表达,Western印迹法测定小鼠肺组织FGF2蛋白表达,ELISA法测定小鼠BALF中TNF-α和IL-6浓度。结果与急性肺损伤组小鼠比较,MSCs-FGF2组小鼠肺组织病理改变明显减轻、肺损伤评分明显降低(P0.05)、肺组织湿重与干重比值明显降低(P0.05)、BALF中中性粒细胞数量明显降低(P0.05)、肺组织FGF2 mR NA及蛋白表达量明显增加(P0.05)、BALF中TNF-α和IL-6浓度明显降低(P均0.05)。结论 MSCs-FGF2基因治疗对脂多糖诱导的急性肺损伤小鼠有确切的保护作用。     

Availability of extracellular matrix biopolymers and differentiation state of human mesenchymal stem cells determine tissue-like growth in vitro

To explore the space-filling growth of adherent mesenchymal stem cells (MSC) into tissue-like structures in vitro, human bone marrow derived MSC were exposed to fibronectin-coated, millimeter-sized, triangular channels casted in poly(dimethyl siloxane) carriers. The results revealed that the three dimensional (3D) growth of MSC differs in dependence on differentiation status and availability of extracellular matrix (ECM) proteins: Massive 3D structure formation was observed for MSC under pro-osteogenic stimulation but not for undifferentiated MSC nor for MSC under pro-adipogenic stimulation; boosting cellular matrix secretion and addition of soluble ECM proteins caused extensive 3D tissue formation of undifferentiated MSC. The reported findings may contribute to bridge the gap between in vitro and in vivo analyses and guide the application of MSC in tissue replacement approaches.     

人脐血间充质干细胞体外分离培养及基因载体特性研究

目的证实脐血中含有间充质干细胞,探讨其体外分离、培养条件,并进行生物学特性和表面抗原的鉴定,初步探索间充质干细胞作为基因治疗的载体携带目的基因的可能性及方法。方法无菌条件下取正常足月剖宫产的脐血分离、培养和纯化,获得间充质干细胞;对获得的间充质干细胞进行形态学观察;绘制生长曲线,分析间充质干细胞的增殖情况;用流式细胞仪检测间充质干细胞表面抗原的表达情况。采用脂质体转染法将pDNA316-IRES-EGFP质粒转入间充质干细胞中,观察绿色荧光的表达以及转染后细胞生长情况。结果自脐血中成功分离获得间充质干细胞,可传代培养,经表面标志检测,表达CD29、CD44、CD105,不表达CD45和HLA-DR。质粒pDNA316-IRES-EGFP通过脂质体介导转染间充质干细胞后,荧光显微镜下观察到报告基因EGFP的表达。转染后的细胞生长受到一定影响。结论人脐血来源的间充质干细胞能在体外分离、培养、扩增,并且具有和骨髓源间充质干细胞类似的生物形态和抗原表型。EGFP基因可被成功转入间充质干细胞中并获表达。转基因间充质干细胞用于基因治疗的持久性和有效性仍需进一步研究。     

Molecular imaging for assessment of mesenchymal stem cells mediated breast cancer therapy

The tumor tropism of mesenchymal stem cells (MSCs) makes them an excellent delivery vehicle used in anticancer therapy. However, the exact mechanisms of MSCs involved in tumor microenvironment are still not well defined. Molecular imaging technologies with the versatility in monitoring the therapeutic effects, as well as basic molecular and cellular processes in real time, offer tangible options to better guide MSCs mediated cancer therapy. In this study, an in situ breast cancer model was developed with MDA-MB-231 cells carrying a reporter system encoding a double fusion (DF) reporter gene consisting of firefly luciferase (Fluc) and enhanced green fluorescent protein (eGFP). In mice breast cancer model, we injected human umbilical cord-derived MSCs (hUC-MSCs) armed with a triple fusion (TF) gene containing the herpes simplex virus truncated thymidine kinase (HSV-ttk), renilla luciferase (Rluc) and red fluorescent protein (RFP) into tumor on day 13, 18, 23 after MDA-MB-231 cells injection. Bioluminescence imaging of Fluc and Rluc provided the real time monitor of tumor cells and hUC-MSCs simultaneously. We found that tumors were significantly inhibited by hUC-MSCs administration, and this effect was enhanced by ganciclovir (GCV) application. To further demonstrate the effect of hUC-MSCs on tumor cells in vivo, we employed the near infrared (NIR) imaging and the results showed that hUC-MSCs could inhibit tumor angiogenesis and increased apoptosis to a certain degree. In conclusion, hUC-MSCs can inhibit breast cancer progression by inducing tumor cell death and suppressing angiogenesis. Moreover, molecular imaging is an invaluable tool in tracking cell delivery and tumor response to hUC-MSCs therapies as well as cellular and molecular processes in tumor.     

携带大鼠酪氨酸羟化酶基因慢病毒载体的构建及转染

目的:构建携带增强绿色荧光蛋白(EGFP)和大鼠酪氨酸羟化酶(TH)基因的慢病毒载体,转染大鼠骨髓间充质干细胞(rMSC),观察TH基因的表达.方法:RT-PCR方法获得大鼠TH基因,将其克隆至慢病毒载体.通过瞬时转染法包装出病毒上清,鉴定滴度.感染rMSCs,荧光显微镜下观察EGFP的表达、转染效率,RT-PCR、免疫印迹法分别检测TH mRNA和蛋白的表达情况.结果:重组慢病毒载体质粒pNL-TH-IRES2-EGFP经双酶切鉴定正确,所获TH基因经测序后与GenBank报道序列完全一致;生产的病毒浓缩后滴度为4.1×10~7TU/ml;感染rMSCs结果显示荧光激发可见绿色荧光,TH-rMSCs、空载体-rMSCs组5d转染效率差异无统计学意义.RT-PCR、免疫印迹法显示TH基因成功在rMSCs中表达.结论:成功构建带有EGFP和大鼠TH基因的慢病毒载体,并获得TH-rMSCs基因工程细胞.     

间充质干细胞标记示踪方法研究进展

间充质干细胞（MSCs）具有很强的自我更新能力和多向分化潜能,现已成为组织修复的理想种子细胞和基因治疗的靶细胞。但MSCs移植入体内的标记和示踪是当今研究的热点和难点问题。目前常用的标记示踪技术按不同的标记分类有：荧光染料标记,分子细胞标记,影像学成像技术标记等。就这些标记示踪方法的优缺点加以综述。     

膝横韧带与半月板损伤间关系的MRI研究

目的:探讨MRI上膝横韧带与半月板损伤程度及位置的关系,进一步认识膝横韧带的临床意义,并为半月板损伤的诊断和治疗提供新的信息.方法:收集288例于本院2009年1月至2010年3月行膝关节MRI检查的病例,在MRI上观察膝横韧带的出现情况及半月板损伤的情况,并分析膝横韧带出现率与半月板损伤程度及位置的相关性.结果:膝横韧带在MRI上的出现率约43.1%(124/288),其长度为(37.5±2.75)mm,宽度为(2.5±1.5)mm.膝横韧带出现率与半月板损伤程度无关(P＞0.05),但与半月板损伤位置有关(P＜0.01).结论:膝横韧带为连接双侧半月板前角的正常解剖结构,在运动过程中协助维持膝关节的稳定,并且对半月板前角具有一定的保护作用.     

基于MRI对交叉韧带松紧度与半月板损伤的相关性研究

目的　探究交叉韧带的松紧度与半月板损伤的相关性,从解剖学上探索半月板损伤的影响因素,为预测和诊断半月板损伤提供新的依据。 方法　收集南方医科大学珠江医院2014年1月~2016年12月260例患者单膝关节伸直位的MRI资料。在各膝MRI相同矢状面分别测量前、后交叉韧带的长度a和p,及其起止点的距离la和lp。计算出交叉韧带松紧度系数R=(a+p)/(la+lp)。用t检验比较各组患者间的差异性,用Spearman 相关分析分别探讨松紧度系数与半月板损伤的相关性。 结果　 t检验：无论是否存在骨关节炎,半月板损伤组和无半月板损伤组的R值均存在显著差异性（P <0.05）。Spearman相关性分析：无骨关节炎患者中rs=0.620,R值与半月板损伤存在较强的正相关性;有骨关节炎患者中rs =0.313,R值与半月板损伤存在弱正相关性。 结论　交叉韧带松紧度与半月板损伤存在一定程度的相关性,特别在膝关节无骨关节炎的年轻患者中,韧带越松弛,半月板损伤越容易发生。但在膝关节有关节炎的老年患者中,交叉韧带的松紧程度并非半月板损伤的主要因素。     

In vivo real-time visualization of mesenchymal stem cells tropism for cutaneous regeneration using NIR-II fluorescence imaging

Mesenchymal stem cells (MSCs) have shown great potential for cutaneous wound regeneration in clinical practice. However, the in vivo homing behavior of intravenously transplanted MSCs to the wounds is still poorly understood. In this work, fluorescence imaging with Ag₂S quantum dots (QDs) in the second near-infrared (NIR-II) window was performed to visualize the dynamic homing behavior of transplanted human mesenchymal stem cells (hMSCs) to a cutaneous wound in mice. Benefiting from the desirable spatial and temporal resolution of Ag₂S QDs-based NIR-II imaging, for the first time, the migration of hMSCs to the wound was dynamically visualized in vivo. By transplanting a blank collagen scaffold in the wound to help the healing, it was found that hMSCs were slowly recruited at the wound after intravenous injection and were predominantly accumulated around the edge of wound. This resulted in poor healing effects in terms of slow wound closure and thin thickness of the regenerated skin. In contrast, for the wound treated by the collagen scaffold loaded with stromal cell derived factor-1α (SDF-1α), more hMSCs were recruited at the wound within a much shorter time and were homogenously distributed across the whole wound area, which enhances the re-epithelialization, the neovascularization, and accelerates the wound healing.     

人骨髓间质干细胞和嗅鞘细胞移植对大鼠急性脊髓损伤功能修复的比较研究

目的对比人骨髓基质细胞(BMSCs)与人胚嗅鞘细胞(OECs)移植对大鼠脊髓损伤功能修复的影响。方法将45只SD大鼠分成脊髓损伤后BMSCs移植组(BMSCs组)、OECs移植组(OECs组)和PBS对照组(PBS组),通过BBB评分、运动诱发电位(MEP)评估脊髓传导功能的改善状况,免疫组织化学方法检测移植细胞存活和分化情况,病理形态学方法观察组织结构修复情况。结果BMSCs组BBB评分高于OECs组(P<0.05);两细胞治疗组MEP潜伏期明显缩短(P<0.05);BMSCs组嗜银染色可见脊髓损伤近端有较多再生纤维向远端延伸,形成神经纤维束,而OECs组再生纤维较少;两种移植细胞均可在损伤处部分存活,BMSCs组可见BMSCs来源的细胞Nestin、NF、GFAP的阳性表达。结论BMSCs移植比OECs移植能更有效促进大鼠急性脊髓损伤修复。     

A codon-optimized luciferase from <Emphasis Type="Italic">Gaussia princeps</Emphasis> facilitates the in vivo monitoring of gene expression in the model alga <Emphasis Type="Italic">Chlamydomonas reinhardtii</Emphasis>

The unicellular green alga Chlamydomonas reinhardtii has emerged as a superb model species in plant biology. Although the alga is easily transformable, the low efficiency of transgene expression from the Chlamydomonas nuclear genome has severely hampered functional genomics research. For example, poor transgene expression is held responsible for the lack of sensitive reporter genes to monitor gene expression in vivo, analyze subcellular protein localization or study protein-protein interactions. Here, we have tested the luciferase from the marine copepod Gaussia princeps (G-Luc) for its suitability as a sensitive bioluminescent reporter of gene expression in Chlamydomonas. We show that a Gaussia luciferase gene variant, engineered to match the codon usage in the Chlamydomonas nuclear genome, serves as a highly sensitive reporter of gene expression from both constitutive and inducible algal promoters. Its bioluminescence signal intensity greatly surpasses previously developed reporters for Chlamydomonas nuclear gene expression and reaches values high enough for utilizing the reporter as a tool to monitor responses to environmental stresses in vivo and to conduct high-throughput screenings for signaling mutants in Chlamydomonas.     

Magnetic and fluorescent graphene for dual modal imaging and single light induced photothermal and photodynamic therapy of cancer cells

Developing a simple and cost-effective strategy to diagnose and treat cancer with single and minimal dosage through noninvasive strategies are highly challenging. To make the theranostic strategy effective, single light induced photothermal and photodynamic reagent with dual modal imaging capability is highly desired. Herein, a simple non-covalent approach was adopted to immobilize hydrophobic silicon napthalocyanine bis (trihexylsilyloxide) (SiNc₄) photosensitizer onto water dispersible magnetic and fluorescent graphene (MFG) via π–π stacking to yield MFG–SiNc₄ functioned as a theranostic nanocarrier. Taking the advantage of broad near infra-red absorption (600–1200 nm) by graphene, photosensitizer of any wavelength within this range will facilitate the single light induced phototherapy. Phosphorescence spectra, singlet oxygen sensor green (SOSG) experiments, and 1,3-diphenyl isobenzofuran quenching studies confirm the generation of singlet ¹O₂ upon photoirradiation. Confocal microscopic images reveal successful internalization of MFG–SiNc₄ in HeLa cells; whereas T₂-weighted magnetic resonance images of MFG reveal a significant concentration dependent darkening effect. In vitro photodynamic/photothermal therapeutic studies on HeLa cells have demonstrated that the killing efficacy of MFG–SiNc₄ using a single light source is ∼97.9%, presumably owing to the combined effects of generating reactive oxygen species, local heating, and induction of apoptosis. The developed MFG–SiNc₄ may thus be utilized as a potential theranostic nanocarrier for dual modal imaging and phototherapy of cancer cells with single light source for time and cost effective treatments with a minimal therapy dose.     

MRI对胰腺导管内乳头状粘液瘤良恶性的诊断价值

目的 探讨MRI对胰腺导管内乳头状粘液性肿瘤（IPMN）良恶性的鉴别诊断价值。方法 收集2012年1月~2018年6月我院经手术病理证实的IPMN患者24例,均行MRI检查（包括MRI平扫、三期增强以及MRCP）,分析IPMN MRI表现、IPMN良恶性因素,并采用ROC曲线分析IPMN肿瘤最大径及胰管扩张直径与肿瘤良恶性关系。结果 24例IPMN患者中,良性14例,恶性10例。良性与恶性在性别、肿瘤分型、病变位置间比较,差异无统计学意义（P＞0.05）;恶性年龄大于良性,差异有统计学意义（P＜0.05）。IPMN恶性肿瘤最大径为（55.70±10.73）mm,大于良性的（34.20±7.65）mm,差异有统计学意义（P＜0.05）;IPMN肿瘤最大径与肿瘤良恶性关系ROC曲线分析得出:曲线下面积（AUC）为0.87,肿瘤最大径最佳临界值为46.40 mm,敏感度为85.68%,特异性为83.35%。IPMN恶性主胰管扩张最大径为（8.91±3.22）mm,大于良性的（4.82±1.33）mm,差异有统计学意义（P＜0.05）;IPMN胰管扩张直径与肿瘤良恶性关系ROC曲线分析得出:AUC为0.88,胰管扩张最大径最佳临界值为7.35 mm,敏感度为70.00%,特异性为85.73%。结论 MRI能很好显示胰管扩张、囊性病变、管壁内结节等特征,在评估IPMN良恶性中具有敏感性。     

Integrated quantitative susceptibility and R2* mapping for evaluation of liver fibrosis: An ex vivo feasibility study

To develop a method for noninvasive evaluation of liver fibrosis, we investigated the differential sensitivities of quantitative susceptibility mapping (QSM) and R₂* mapping using corrections for the effects of liver iron. Liver fibrosis is characterized by excessive accumulation of collagen and other extracellular matrix proteins. While collagen increases R₂* relaxation, measures of R₂* for fibrosis are confounded by liver iron, which may be present in the liver over a wide range of concentrations. The diamagnetic collagen contribution to susceptibility values measured by QSM is much less than the contribution of highly paramagnetic iron. In 19 ex vivo liver explants with and without fibrosis, QSM (χ), R₂* and proton density fat fraction (PDFF) maps were constructed from multiecho gradient‐recalled echo (mGRE) sequence acquisition at 3 T. Median parameter values were recorded and differences between the MRI parameters in nonfibrotic vs. advanced fibrotic/cirrhotic samples were evaluated using Mann–Whitney U tests and receiver operating characteristic analyses. Logistic regression with stepwise feature selection was employed to evaluate the utility of combined MRI measurements for detection of fibrosis. Median R₂* increased in fibrotic vs. nonfibrotic liver samples (P = .041), while differences in χ and PDFF were nonsignificant (P = .545 and P = .395, respectively). Logistic regression identified the combination of χ and R₂* significant for fibrosis detection (logit [prediction] = ?8.45 + 0.23 R₂* ? 28.8 χ). For this classifier, a highly significant difference between nonfibrotic vs. advanced fibrotic/cirrhotic samples was observed (P = .002). The model exhibited an AUC of 0.909 (P = .003) for detection of advanced fibrosis/cirrhosis, which was substantially higher compared with AUCs of the individual parameters (AUC 0.591–0.784). An integrated QSM and R₂* analysis of mGRE 3 T imaging data is promising for noninvasive diagnostic assessment of liver fibrosis.