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MEDICAL SCIENCE MONITOR · 2016 · IF 1.405

Lactation-Related MicroRNA Expression in Microvesicles of Human Umbilical Cord Blood

De-jing Wang,Chen-meiyi Wang,Yi-ting Wang,Hai Qiao,Liao-qiong Fang,Zhi-biao Wang

Background The complex process by which lactation is initiated upon neonate delivery remains incompletely understood. Microvesicles (MVs) can transmit microRNAs (miRNAs) into recipient cells to influence cell function, and recent studies have identified miRNAs essential for mammary gland development and lactation. This study aimed to investigate the expression of lactation-related miRNAs in MVs isolated from human umbilical cord blood immediately after delivery. Material/Methods Umbilical cord blood samples were collected from 70 healthy pregnant women, and MVs were isolated through differential centrifugation and characterized by transmission electron microscopy, Western blotting, and nanoparticle tracking analysis. Lactation-related miRNAs were screened using bioinformatics tools for miRNA target prediction, gene ontology, and signaling pathway analyses. miRNA PCR arrays were used for miRNA expression analysis, and the results were validated by real-time PCR. Upon exposure of HBL-100 human mammary epithelial cells to MVs, MV uptake was examined by fluorescence confocal microscopy and β-casein secretion was detected by ELISA. Results Spherical MVs extracted from umbilical cord blood expressed CD63 and had an average diameter of 167.0±77.1 nm. We profiled 337 miRNAs in human umbilical cord blood MVs and found that 85 were related to lactation by bioinformatics analysis. The 25 most differentially expressed lactation-related miRNAs were validated by real-time PCR. MV uptake by HBL-100 cells was after 4 h in culture, and significantly increased secretion of β-casein was observed after 96 h from cells exposed to MVs (P<0.05). Conclusions Umbilical cord blood MVs contain many lactation-related miRNAs and can induce β-casein production by HBL-100 cells in vitro . Thus, umbilical cord blood MVs may mediate secretion of β-casein through miRNAs, thereby playing an important role in fetal-maternal crosstalk.

研究领域: 妇产科学 · 分子生物学 · 细胞生物学
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Applied Biological Chemistry · 2024 ·Vol. 67 ·期 1 ·1-17 · IF 2.3

Novel fabrication of macromolecular multi-functional hydrogel encapsulated with HUCB-derived mesenchymal stem cells to effective regeneration of cardiac repair after acute myocardial infarction

Xue Jun,Gao Yu Ping

Acute myocardial infarction (AMI) has been treated via injectable hydrogels and biomaterial patches invented using tissue engineering advancements over the past decade. Yet the curative potential of injectable hydrogels and stem cells is limited. Here, we propose the development of an injectable and conductive hydrogel composed of oxidised macromolecular hyaluronic acid and chitosan-grafted aniline tetramer polymeric components. In an attempt to enhance the therapeutic potential of AMI therapy, mesenchymal stem cells derived from human umbilical cord blood (HUCB-MSC) have been integrated into the formulation of a conductive hydrogel. For reliable connection to the beating hearts, the hydrogel exhibited suitable adhesive properties. Hydrogel’s potent biocompatibility was determined by in vitro investigations of cell viability and proliferation of NRCMs and H9C2 cardiomyocytes. After myocardial injection, longer HUCB-MSCs survival length, cardiac functioning, and histology in SD rat myocardium were demonstrated, greatly associated by up-regulation and downregulation of cardiac-related relative gene expressions of angiogenic factors and inflammatory factors, respectively. The injectable hydrogel that contained HUCB-MSCs substantially enhanced the therapeutic benefits, indicating a potentially beneficial therapeutic approach to AMI therapy.

CAS / MDL: 74124-79-1 25952-53-8
研究领域: 生物医学工程 · 心血管疾病研究 · 组织工程
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Materials Science & Engineering C-Materials for Biological Applications · 2016 · IF 3.42

Alginate/PEG based microcarriers with cleavable crosslinkage for expansion and non-invasive harvest of human umbilical cord blood mesenchymal stem cells

Chunge Li,Yufeng Qian,Shuang Zhao,Yuji Yin,Junjie Li

Porous microcarriers are increasingly used to expand and harvest stem cells. Generally, the cells are harvested via proteolytic enzyme treatment, which always leads to damages to stem cells. To address this disadvantage, a series of alginate/PEG (AL/PEG) semi-interpenetrating network microcarriers are prepared in this study. In this AL/PEG system, the chemically cross-linked alginate networks are formed via the reaction between carboxylic acid group of alginate and di-terminated amine groups of cystamine. PEG is introduced to modulate the degradation of microcarriers, which does not participate in this cross-linked reaction, while it interpenetrates in alginate network via physical interactions. In addition, chitosan are coated on the surface of AL/PEG to improve the mechanical strength via the electrostatic interactions. Biocompatible fibronectin are also coated on these microcarriers to modulate the biological behaviors of cells seeded in microcarriers. Results suggest that the size of AL/PEG microcarriers can be modulated via adjusting the contents and molecular weight of PEG. Moreover, the microcarriers are designed to be degraded with cleavage of disulfide crosslinkage. By changing the type and concentration of reductant, the ratio of AL to PEG, and the magnitude of chitosan coating, the degradation ability of AL/PEG microcarriers can be well controlled. In addition, AL/PEG microcarriers can support the attachment and proliferation of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs). More importantly, the expanded hUCB-MSCs can be detached from microcarriers after addition of reductant, which indeed reduce the cell damage caused by proteolytic enzyme treatment. Therefore, it is convinced that AL/PEG based microcarriers will be a promising candidate for large-scale expansion of hUCB-MSCs.

研究领域: 生物材料学 · 细胞工程 · 再生医学
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS · 2023 · IF 3.1

Bioactive self-healing umbilical cord blood exosomes hydrogel for promoting chronic diabetic wound healing

Kexin Liu,Benxin Gong,Tao Li,Huafeng Lei,Jiahua Li,Jingyun Tang,Yanrong Peng,Shengnian Li,Ying Zheng,Guangzhou Wei

The deleterious effects of diabetes mellitus on wound healing have become a major public health concern worldwide. Given the complex microenvironment of diabetic wounds and the high prevalence of diabetes, the design and development of novel wound dressing materials with versatile capabilities is urgent. Extracellular vesicles (EVs) derived from human umbilical cord blood have demonstrated the potential to counter inflammation and accelerate wound healing. Herein, we explored the efficacy of incorporating human umbilical cord blood-derived exosomes (UCB-Exos) into an ABA-type amphiphilic hydrogel, which possesses the attributes of exosome (Exo) encapsulation, temperature-triggered reversible sol-gel conversion, and Exo-regulated release, for enhancing the stability and retention of Exos. We sought to examine the feasibility of this strategy in augmenting the therapeutic efficacy of UCB-Exos for the healing of diabetes-related wounds. The injectable hydrogel was conveniently applied directly onto the wound surface and the enclosed Exo significantly facilitated the healing process, resulting in faster wound closure, enhanced collagen deposition, accelerated re-epithelialization, and enhanced neo-vascularization within two weeks compared with the hydrogel-only treatment group. In summary, some hydrogels hold great promise for promoting wound healing in diabetics and represent a novel therapeutic option for diabetes-related ulcers.

研究领域: 生物医学工程 · 药剂学 · 组织工程
✓ 已验证 DOI PubMed 高影响因子
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SCIENCE OF THE TOTAL ENVIRONMENT · 2018 · IF 4.61

Transfer of polycyclic aromatic hydrocarbons from mother to fetus in relation to pregnancy complications

Xudong Dong,Qibing Wang,Juan Peng,Min Wu,Bo Pan,Baoshan Xing

The accumulation and transfer of carcinogens, including polycyclic aromatic hydrocarbons (PAHs), in the human body, especially from mother to fetus, has been the subject of many research studies, but the related data are limited and the mechanisms are unknown. This is the first study to investigate the distribution of PAHs in paired samples of maternal blood, placenta tissue, and umbilical cord blood in relation to pregnancy complications. Sixty-four pairs of samples were collected in Kunming, China; 18 were from healthy pregnant women and 46 were from patients with pregnancy complications. The predominant PAHs in these pregnant women were high-molecular-weight (HMW) compounds, mainly from the incomplete combustion or pyrolysis of biomass. In the control group, the total amount of HMW compounds (Σ HMW PAHs) was significantly higher in maternal blood than in umbilical cord blood, which suggested that placenta may decrease PAH transfer in healthy pregnant women. However, this phenomenon was not observed for low-molecular-weight PAHs or in the case group. In the control group, Σ 16 PAH and Σ HMW PAH in the placenta were higher than those in maternal blood and umbilical cord blood; for the case group, a contrasting result was observed. Σ HMW PAHs in the placenta was significantly higher in the control group than in the case group. The same results were observed after the exclusion of the impact of the genotypes of the PAH metabolic enzymes (both phase I and phase II enzymes). Thus, the decreased PAH transfer from mother to fetus may partially result from the accumulation of PAHs inside the placenta.

CAS / MDL: 75-09-2 110-54-3 67-56-1
研究领域: 环境科学 · 毒理学 · 妇产科学 · 分子生物学
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Regenerative Biomaterials · 2022 · IF 5.763

Three-dimensional-printed collagen/chitosan/secretome derived from HUCMSCs scaffolds for efficient neural network reconstruction in canines with traumatic brain injury

Liu Xiaoyin,Zhang Guijun,Wei Pan,Zhong Lin,Chen Yaxing,Zhang Jianyong,Chen Xuyi,Zhou Liangxue

The secretome secreted by stem cells and bioactive material has emerged as a promising therapeutic choice for traumatic brain injury (TBI). We aimed to determine the effect of 3D-printed collagen/chitosan/secretome derived from human umbilical cord blood mesenchymal stem cells scaffolds (3D-CC-ST) on the injured tissue regeneration process. 3D-CC-ST was performed using 3D printing technology at a low temperature (−20°C), and the physical properties and degeneration rate were measured. The utilization of low temperature contributed to a higher cytocompatibility of fabricating porous 3D architectures that provide a homogeneous distribution of cells. Immediately after the establishment of the canine TBI model, 3D-CC-ST and 3D-CC (3D-printed collagen/chitosan scaffolds) were implanted into the cavity of TBI. Following implantation of scaffolds, neurological examination and motor evoked potential detection were performed to analyze locomotor function recovery. Histological and immunofluorescence staining were performed to evaluate neuro-regeneration. The group treated with 3D-CC-ST had good performance of behavior functions. Implanting 3D-CC-ST significantly reduced the cavity area, facilitated the regeneration of nerve fibers and vessel reconstruction, and promoted endogenous neuronal differentiation and synapse formation after TBI. The implantation of 3D-CC-ST also markedly reduced cell apoptosis and regulated the level of systemic inflammatory factors after TBI.

研究领域: 神经科学 · 干细胞生物学 · 组织工程 · 生物医学工程 · 再生医学
✓ 已验证 DOI PubMed 高影响因子
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Advanced Science · 2022 ·Vol. 9 ·期 23 ·2201271 · IF 17.521

An Injectable Epigenetic Autophagic Modulatory Hydrogel for Boosting Umbilical Cord Blood NK Cell Therapy Prevents Postsurgical Relapse of Triple-Negative Breast Cancer

Yihang Gong,Wenjie Chen,Xiuxing Chen,Yizhan He,Hua Jiang,Xijian Zhang,Lijie Pan,Beibei Ni,Fan Yang,Yan Xu,Qi Zhang,Lei Zhou,Yusheng Cheng

Triple-negative breast cancer (TNBC) exhibits resistance to conventional treatments due to the presence of cancer stem cells (CSCs), causing postsurgical relapse and a dismal prognosis. Umbilical cord blood natural killer (UCB-NK) cell-based immunotherapy represents a promising strategy for cancer treatment. However, its therapeutic efficacy is greatly restrained by downregulation of the NK cell activation ligand MHC class I-related chain A/B (MICA/B) and autophagy-mediated degradation of NK cell-derived granzyme B (GZMB) in CSCs. Herein, it is demonstrated that suberoylanilide hydroxamic acid (SAHA) epigenetically downregulates let-7e-5p and miR-615-3p to increase MICA/B expression and that 3-methyl adenine (3MA) inhibits autophagy-mediated GZMB degradation, thereby sensitizing breast CSCs to UCB-NK cells. Then, an injectable hydrogel is designed to codeliver SAHA and 3MA to enhance UCB-NK cell infusion efficacy in TNBC. The hydrogel precursors can be smoothly injected into the tumor resection bed and form a stable gel in situ, allowing for a pH-sensitive sustained release of SAHA and 3MA. Moreover, UCB-NK cell infusion in combination with the hydrogel efficiently controls postsurgical relapse of TNBC. In addition, the hydrogel exhibits good hemostasis and wound-healing functions. Therefore, the work provides proof of concept that an injectable epigenetic autophagic modulatory hydrogel augments UCB-NK cell therapy to combat postsurgical relapse of TNBC.

研究领域: 肿瘤学 · 免疫治疗 · 药学 · 生物医学工程
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ACS Biomaterials Science & Engineering · 2021 · IF 4.749

Bioprinting of Human Cord Blood-Derived CD34+ Cells and Exploration of the Multilineage Differentiation Ability in Vitro

Lidan Chen,Dezhi Zhou,Xinda Li,Bin Yang,Tao Xu

The three-dimensional (3D) marrow microenvironment plays an essential role in regulating human cord blood-derived CD34+ cells (hCB-CD34+) migration, proliferation, and differentiation. Extensive in vitro and in vivo studies have aimed to recapitulate the main components of the bone marrow (BM) niche. Nonetheless, the models are limited by a lack of heterogeneity and compound structure. Here, we fabricated coaxial extruded core–shell tubular scaffolds and extrusion-based bioprinted cell-laden mesh scaffolds to mimic the functional niche in vitro. A multicellular mesh scaffold and two different core–shell tubular scaffolds were developed with human bone marrow-derived mesenchymal stromal cells (BMSCs) in comparison with a conventional 2D coculture system. A clear cell–cell connection was established in all three bioprinted constructs. Cell distribution and morphology were observed in different systems with scanning electron microscopy (SEM). Collected hCB-CD34+ cells were characterized by various stem cell-specific and lineage-specific phenotypic parameters. The results showed that compared with hCB-CD34+ cells cocultured with BMSCs in Petri dishes, the self-renewal potential of hCB-CD34+ cells was stronger in the tubular scaffolds after 14 days. Besides, cells in these core–shell constructs tended to obtain stronger differentiation potential of lymphoid and megakaryocytes, while cells encapsulated in mesh scaffolds obtained stronger differentiation tendency into erythroid cells. Consequently, 3D bioprinting technology could partially simulate the niche of human hematopoietic stem cells. The three models have their potential in stemness maintenance and multilineage differentiation. This study can provide initial effective guidance in the directed differentiation research and related screening of drug models for hematological diseases.

CAS / MDL: 9005-38-3
研究领域: 组织工程 · 血液学 · 干细胞生物学 · 生物医学工程
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