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Regulatory factors of mesenchymal stem cell migration into injured tissues and their signal transduction

null

《医学前沿（英文）》 2011年 第5卷 第1期   页码 33-39 doi: 10.1007/s11684-011-0114-1

摘要：

Adult stem cells hold great promise for wound healing and tissue regeneration. Mesenchymal stem cells (MSCs), for example, have been shown to play a role in tissue repair. Research has shown that endogenous bone marrow MSCs or exogenously delivered MSCs migrate to the sites of injury and participate in the repair process. The precise mechanisms underlying migration of MSCs into the injured tissue are still not fully understood, although multiple signaling pathways and molecules were reported, including both chemoattractive factors and endogenous electric fields at wounds. This review will briefly summarize the regulatory facors and signaling transduction pathways involved in migration of MSCs. A better understanding of the molecular mechanisms involved in the migration of MSCs will help us to develop new stem cell-based therapeutic strategies in regenerative medicine.

关键词： mesenchymal stem cells     migration     molecular mechanisms     signaling pathway    

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Epithelial-to-mesenchymal transition in cancer: complexity and opportunities

Yun Zhang, Robert A. Weinberg

《医学前沿（英文）》 2018年 第12卷 第4期   页码 361-373 doi: 10.1007/s11684-018-0656-6

摘要：

The cell-biological program termed the epithelial-to-mesenchymal transition (EMT) plays an important role in both development and cancer progression. Depending on the contextual signals and intracellular gene circuits of a particular cell, this program can drive fully epithelial cells to enter into a series of phenotypic states arrayed along the epithelial-mesenchymal phenotypic axis. These cell states display distinctive cellular characteristics, including stemness, invasiveness, drug-resistance and the ability to form metastases at distant organs, and thereby contribute to cancer metastasis and relapse. Currently we still lack a coherent overview of the molecular and biochemical mechanisms inducing cells to enter various states along the epithelial-mesenchymal phenotypic spectrum. An improved understanding of the dynamic and plastic nature of the EMT program has the potential to yield novel therapies targeting this cellular program that may aid in the management of high-grade malignancies.

关键词： epithelial-to-mesenchymal transition     cancer     metastasis     cancer stem cell    

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Cell therapy for the treatment of reproductive diseases and infertility: an overview from the mechanism

《医学前沿（英文）》 2022年 第16卷 第6期   页码 827-858 doi: 10.1007/s11684-022-0948-8

摘要： Infertility is experienced by 8%–12% of adults in their reproductive period globally and has become a prevalent concern. Besides routine therapeutic methods, stem cells are rapidly being examined as viable alternative therapies in regenerative medicine and translational investigation. Remarkable progress has been made in understanding the biology and purpose of stem cells. The affected pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs) are further studied for their possible use in reproductive medicine, particularly for infertility induced by premature ovarian insufficiency and azoospermia. Accordingly, this study discusses current developments in the use of some kinds of MSCs such as adipose-derived stem cells, bone marrow stromal cells, umbilical cord MSCs, and menstrual blood MSCs. These methods have been used to manage ovarian and uterine disorders, and each technique presents a novel method for the therapy of infertility.

关键词： infertility     stem cell therapy     mesenchymal stem cells     pluripotent stem cells    

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Umbilical cord-derived mesenchymal stem cells: strategies, challenges, and potential for cutaneous regeneration

null

《医学前沿（英文）》 2012年 第6卷 第1期   页码 41-47 doi: 10.1007/s11684-012-0175-9

摘要：

Umbilical cord mesenchymal stem cells (MSCs) are a unique, accessible, and non-controversial source of early stem cells that can be readily manipulated. As the most common pluripotent cell, bone marrow-derived MSCs display limitations with the progress of stem cell therapy. By contrast, umbilical cord-derived cells, which have plentiful resources, are more accessible. However, several uncertain aspects, such as the effect of donor selection or culture conditions, long-term therapeutic effects, product consistency, and potential tumorigenicity, are the bottleneck in this clinical therapy. MSCs are predicted to undergo an unprecedented development in clinical treatment when a generally acknowledged criterion emerges. In the current paper, we highlight the application of umbilical cord-derived MSCs in skin therapies based on our previous studies, as well as the achievements of our peers in this field. This paper focuses on the strategies, challenges, and potential of this novel therapy.

关键词： umbilical cord     mesenchymal stem cells     cutaneous regeneration    

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Immunohistochemical characterization of hepatic stem cell-related cells in developing human liver

XU Jun, HU Yong, WANG Jian, ZHANG Taiping, ZHOU Ji, YU Hongyu

《医学前沿（英文）》 2007年 第1卷 第3期   页码 264-268 doi: 10.1007/s11684-007-0050-2

摘要： Little is known about the expression characteristics of the various kinds of possible markers in hepatic stem cells (HSCs) and other HSC-related cells in human fetal liver in various developmental stages. It is significant to investigate the immunohistochemical expression for better understanding of the origin, differentiation and migration of HSCs in the developing human liver. H-E staining and immunohistochemical methods were used to observe the expression of hepatic/cholangiocellular differentiation markers (AFP, GST-, CK7, CK19) and hematopoietic stem cell markers (CD34 and c-kit) in several kinds of HSC-related cells in thirty cases of fetal liver samples (4–35 weeks after pregnancy). AFP expression appears in fetal hepatocytes at four weeks’ gestation. It peaks at 16–24 weeks’ gestation and decreases gradually afterwards. Finally, weak signals were only found in some ductal plate cells and a few limiting plate cells. GST- was detected in hepatic cord cells from the sixth week and in the ductal plate cells from the eighth week. Twenty-six weeks later, only some ductal plate cells and a few limiting plate cells show positive signals. CK19 expression peaks during the 6th–11th weeks in hepatic cord cells and decreases gradually afterwards, except for the ductal plates. CK7 expression was limited in the ductal plate cells and bile ducts cells from the 14th week. CD34 and c-kit were detected at the eighth week in some ductal plate cells and a few mononuclear cells in the hepatic cords/mesenchymal tissue of portal areas. After 21 weeks, CD34 and c-kit were found only in ductal plate cells and a few mononuclear cells in the hepatic mesenchymal tissue of portal areas. Fetal hepatocytes at 4–16 weeks’ gestation are mainly constituted by HSCs characterized with bi-potential differentiation capacity. At 16 weeks’ gestation, most hepatic cord cells begin to differentiate into hepatocytes and abundant HSCs remain in ductal plate (the origin site of Hering canals). It is also indicated that the hematopoietic stem cells may give rise to some HSCs in embryonic liver. These indirectly support the hypothesis about the location and origin of HSCs in liver valley hypothesis reported previously.

关键词： origin     Little     mesenchymal tissue     cords/mesenchymal tissue     CD34    

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Extracellular vesicle-carried GTF2I from mesenchymal stem cells promotes the expression of tumor-suppressive

《医学前沿（英文）》 doi: 10.1007/s11684-023-0999-5

摘要： Through bioinformatics predictions, we identified that GTF2I and FAT1 were downregulated in thyroid carcinoma (TC). Further, Pearson’s correlation coefficient revealed a positive correlation between GTF2I expression and FAT1 expression. Therefore, we selected them for this present study, where the effects of bone marrow mesenchymal stem cell-derived EVs (BMSDs-EVs) enriched with GTF2I were evaluated on the epithelial–to–mesenchymal transition (EMT) and stemness maintenance in TC. The under-expression of GTF2I and FAT1 was validated in TC cell lines. Ectopically expressed GTF2I and FAT1 were found to augment malignant phenotypes of TC cells, EMT, and stemness maintenance. Mechanistic studies revealed that GTF2I bound to the promoter region of FAT1 and consequently upregulated its expression. MSC-EVs could shuttle GTF2I into TPC-1 cells, where GTF2I inhibited TC malignant phenotypes, EMT, and stemness maintenance by increasing the expression of FAT1 and facilitating the FAT1-mediated CDK4/FOXM1 downregulation. In vivo experiments confirmed that silencing of GTF2I accelerated tumor growth in nude mice. Taken together, our work suggests that GTF2I transferred by MSC-EVs confer antioncogenic effects through the FAT1/CDK4/FOXM1 axis and may be used as a promising biomarker for TC treatment.

关键词： thyroid carcinoma     mesenchymal stem cell     extracellular vesicle     GTF2I     FAT1     CDK4    

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Mesenchymal stem cells and immune disorders: from basic science to clinical transition

Shihua Wang, Rongjia Zhu, Hongling Li, Jing Li, Qin Han, Robert Chunhua Zhao

《医学前沿（英文）》 2019年 第13卷 第2期   页码 138-151 doi: 10.1007/s11684-018-0627-y

摘要： As a promising candidate seed cell type in regenerative medicine, mesenchymal stem cells (MSCs) have attracted considerable attention. The unique capacity of MSCs to exert a regulatory effect on immunity in an autologous/allergenic manner makes them an attractive therapeutic cell type for immune disorders. In this review, we discussed the current knowledge of and advances in MSCs, including its basic biological properties, i.e., multilineage differentiation, secretome, and immunomodulation. Specifically, on the basis of our previous work, we proposed three new concepts of MSCs, i.e., “subtotipotent stem cell” hypothesis, MSC system, and “Yin and Yang” balance of MSC regulation, which may bring new insights into our understanding of MSCs. Furthermore, we analyzed data from the Clinical Trials database (http://clinicaltrials.gov) on registered clinical trials using MSCs to treat a variety of immune diseases, such as graft-versus-host disease, systemic lupus erythematosus, and multiple sclerosis. In addition, we highlighted MSC clinical trials in China and discussed the challenges and future directions in the field of MSC clinical application.

关键词： mesenchymal stem cell     clinical transition     immune disorders    

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Clinical study using mesenchymal stem cells for the treatment of patients with severe COVID-19

Lingling Tang, Yingan Jiang, Mengfei Zhu, Lijun Chen, Xiaoyang Zhou, Chenliang Zhou, Peng Ye, Xiaobei Chen, Baohong Wang, Zhenyu Xu, Qiang Zhang, Xiaowei Xu, Hainv Gao, Xiaojun Wu, Dong Li, Wanli Jiang, Jingjing Qu, Charlie Xiang, Lanjuan Li

《医学前沿（英文）》 2020年 第14卷 第5期   页码 664-673 doi: 10.1007/s11684-020-0810-9

摘要： The coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was identified in December 2019. The symptoms include fever, cough, dyspnea, early symptom of sputum, and acute respiratory distress syndrome (ARDS). Mesenchymal stem cell (MSC) therapy is the immediate treatment used for patients with severe cases of COVID-19. Herein, we describe two confirmed cases of COVID-19 in Wuhan to explore the role of MSC in the treatment of COVID-19. MSC transplantation increases the immune indicators (including CD4 and lymphocytes) and decreases the inflammation indicators (interleukin-6 and C-reactive protein). High-flow nasal cannula can be used as an initial support strategy for patients with ARDS. With MSC transplantation, the fraction of inspired O (FiO ) of the two patients gradually decreased while the oxygen saturation (SaO ) and partial pressure of oxygen (PO ) improved. Additionally, the patients’ chest computed tomography showed that bilateral lung exudate lesions were adsorbed after MSC infusion. Results indicated that MSC transplantation provides clinical data on the treatment of COVID-19 and may serve as an alternative method for treating COVID-19, particularly in patients with ARDS.

关键词： coronavirus disease 2019 (COVID-19)     mesenchymal stem cell     acute respiratory distress syndrome     stem cell therapeutics    

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Mesenchymal stem cells hold promise for regenerative medicine

Shihua Wang, Xuebin Qu, Robert Chunhua Zhao

《医学前沿（英文）》 2011年 第5卷 第4期   页码 372-378 doi: 10.1007/s11684-011-0164-4

摘要： Regenerative medicine is an emerging interdisciplinary field of research that uses several technological approaches including stem cells to repair tissues. Mesenchymal stem cells (MSCs), a type of adult stem cell, have generated a great amount of interest over the past decade in this field. Numerous studies have explored the role of MSCs in tissue repair and modulation of allogeneic immune responses. The mechanisms through which MSCs exert their therapeutic potential rely on some key properties of the cells as follows: the capacity to differentiate into osteoblasts, chondrocytes, adipocytes, cardiomyocytes, hepatocytes, endothelial, and neuronal cells; the ability to secrete multiple bioactive molecules capable of stimulating the recovery of injured cells and inhibiting inflammation; the lack of immunogenicity; and the ability to perform immunomodulatory functions. In the present review, we focus on these three aspects upon which the therapeutic effects of MSCs are mainly based. Furthermore, some pathological conditions under which the application of MSCs should be done with caution are also mentioned.

关键词： mesenchymal stem cells     differentiation     immunomodulation     regenerative medicine    

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Implantation of human umbilical cord mesenchymal stem cells for ischemic stroke: perspectives and challenges

null

《医学前沿（英文）》 2015年 第9卷 第1期   页码 20-29 doi: 10.1007/s11684-014-0371-x

摘要：

Ischemic stroke is a focal cerebral insult that often leads to many adverse neurological complications severely affecting the quality of life. The prevalence of stroke is increasing throughout the world, while the efficacy of current pharmacological therapies remains unclear. As a neuroregenerative therapy, the implantation of human umbilical cord mesenchymal stem cells (hUC-MSCs) has shown great possibility to restore function after stroke. This review article provides an update role of hUC-MSCs implantation in the treatment of ischemic stroke. With the unique “immunosuppressive and immunoprivilege” property, hUC-MSCs are advised to be an important candidate for allogeneic cell treatment. Nevertheless, most of the treatments are still at primary stage and not clinically feasible at the current time. Several uncertain problems, such as culture conditions, allograft rejection, and potential tumorigenicity, are the choke points in this cellular therapy. More preclinical researches and clinical studies are needed before hUC-MSCs implantation can be used as a routinely applied clinical therapy.

关键词： cellular therapy     transplantation     human umbilical cord     mesenchymal stem cells     ischemic stroke    

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Capacity of human umbilical cord-derived mesenchymal stem cells to differentiate into sweat gland-like

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《医学前沿（英文）》 2013年 第7卷 第3期   页码 345-353 doi: 10.1007/s11684-013-0282-2

摘要：

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) possess various advantageous properties, including self-renewal, extended proliferation potential, multi-lineage differentiation potential and capacity for differentiating into sweat gland-like cells in certain conditions. However, little is known about the effect of clinical-grade culture conditions on these properties and on the differentiative potential of hUC-MSCs. In this study, we sought to investigate the properties of hUC-MSCs expanded with animal serum free culture media (ASFCM) in order to determine their potential for differentiation into sweat gland-like cells. We found that primary cultures of hUC-MSCs could be established with ASFCM. Moreover, cells cultured in ASFCM showed vigorous proliferation comparable to those of cells grown in classical culture conditions containing fetal bovine serum (FBS). Morphology of hUC-MSCs cultured in ASFCM was comparable to those of cells grown under classical culture conditions, and hUC-MSCs grown in both of the two culture conditions tested showed the typical antigen profile of MSCs—positive for CD29, CD44, CD90, and CD105, and negative for CD34 and CD45, as expected. Chromosomal aberration assay revealed that the cells were stable after long-term culture under both culture conditions. Like normal cultured MSCs, hUC-MSCs induced under ASFCM conditions exhibited expression of the same markers (CEA, CK14 and CK19) and developmental genes (EDA and EDAR) that are characteristic of normal sweat gland cells. Taken together, our findings indicate that the classical culture medium used to differentiate hUC-MSCs into sweat gland-like cells can be replaced safely by ASFCM for clinical purposes.

关键词： umbilical cord     mesenchymal stem cells     sweat gland     preclinical    

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Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study

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《医学前沿（英文）》 2011年 第5卷 第1期   页码 94-100 doi: 10.1007/s11684-011-0116-z

摘要：

Mesenchymal stem cells (MSC) have been used in clinical trials for severe diabetes, a chronic disease with high morbidity and mortality. Bone marrow is the traditional source of human MSC, but human term placenta appears to be an alternative and more readily available source. Here, the therapeutic effect of human placenta-derived MSC (PD-MSC) was studied in type 2 diabetes patients with longer duration, islet cell dysfunction, high insulin doses as well as poor glycemic control in order to evaluate the safety, efficacy and feasibility of PD-MSC treatment in type 2 diabetes (T2D). Ten patients with T2D received three intravenous infusions of PDSC, with one month interval of infusion. The total number of PDSC for each patient was (1.22–1.51) × 106/kg, with an average of 1.35 × 106/kg. All of the patients were followed up after therapy for at least 3 months. A daily mean dose of insulin used in 10 patients was decreased from 63.7?±?18.7 to 34.7?±?13.4 IU (P<0.01), and the C-peptide level was increased from 4.1?±?3.7 ng/mL to 5.6?±?3.8 ng/mL (P<0.05) respectively after therapy. In 4 of 10 responders their insulin doses reduced more than 50% after infusion. The mean levels of insulin and C-peptide at each time point in a total of 10 patients was higher after treatment (P<0.05). No fever, chills, liver damage and other side effects were reported. The renal function and cardiac function were improved after infusion. The results obtained from this pilot clinical trial indicate that transplantation of PD-MSC represents a simple, safe and effective therapeutic approach for T2D patients with islet cell dysfunction. Further large-scale, randomized and well-controlled clinical studies will be required to substantiate these observations.

关键词： placenta stem cells     treatment of type 2 diabetes    

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The unregulated commercialization of stem cell treatments: a global perspective

Douglas Sipp

《医学前沿（英文）》 2011年 第5卷 第4期   页码 348-355 doi: 10.1007/s11684-011-0150-x

摘要： Research into the biological properties and clinical potential of stem cells has spurred strong public investment, industry development, media coverage, and patient interest in recent years. To date, however, few clinical applications of demonstrated safety and efficacy have been developed with the exception of uses of hematopoietic stem cells in the treatment of diseases of the blood and immune systems. This lack of an evidence basis notwithstanding, hundreds of companies and private clinics around the world now sell putative stem cell treatments for an enormously broad range of medical and quality-of-life conditions. This represents a major challenge for legitimate scientists working in the field, for authorities seeking to protect their constituencies, and for patients and consumers targeted by such companies’ marketing strategies. In this review, I provide an overview of the global industry in pseudomedical stem cell treatments, with an investigation of claims in a single disease area (amyotrophic lateral sclerosis), and make recommendations for the introduction and enforcement of appropriate regulatory responses to this problem.

关键词： stem cell tourism     medical ethics     stem cell policy and regulation     alternative medicine    

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The regulatory sciences for stem cell-based medicinal products

null

《医学前沿（英文）》 2014年 第8卷 第2期   页码 190-200 doi: 10.1007/s11684-014-0323-5

摘要：

Over the past few years, several new achievements have been made from stem cell studies, many of which have moved up from preclinical stages to early, or from early to middle or late, stages thanks to relatively safe profile and preliminary evidence of effectiveness. Moreover, some stem cell-based products have been approved for marketing by different national regulatory authorities. However, many critical issues associated mainly with incomplete understanding of stem cell biology and the relevant risk factors, and lack of effective regulations still exist and need to be urgently addressed, especially in countries where establishment of appropriate regulatory system just commenced. More relevantly, the stem cell regulatory sciences need to be established or improved to more effectively evaluate quality, safety and efficacy of stem cell products, and for building up the appropriate regulatory framework. In this review, we summarize some new achievements in stem cell studies, especially the preclinical and clinical studies, the existing regulations, and the associated challenges, and we then propose some considerations for improving stem cell regulatory sciences with a goal of promoting the steadfast growth of the well-regulated stem cell therapies abreast of evolvement of stem cell sciences and technologies.

关键词： stem cell-based medicinal products (SCMPs)     stem cell therapy (SCT)     safety     effectiveness     standards     guidelines     regulatory science    

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Therapeutic potential of stem cell in liver regeneration

null

《医学前沿（英文）》 2011年 第5卷 第1期   页码 26-32 doi: 10.1007/s11684-011-0107-0

摘要：

Liver transplantation is the only life-saving procedure for patients with end-stage liver disease. However, its potential benefits are hampered by many disadvantages, such as the relative shortage of donors, operative risks, and high costs. These issues have prompted the search for new alternative therapies for irreversible liver disease. Stem cell therapy, with the ability for self-renewal and potential for multilineage differentiation, is a promising alternative approach. Several studies have demonstrated that transplantation of hepatic stem/progenitor cells or hepatocyte-like cells derived from multipotent stem cells leads to donor cell-mediated repopulation of the liver and improved survival rates in experimental models of liver disease. However, a registered clinical application based on stem cell technology will take at least an additional 5 to 10 years because of some limitations; e.g. the lack of suitable cell sources and risk of teratoma formation. This review summarizes the general understanding of the therapeutic potentials of stem cells in liver disease, including the sources, mechanisms, and delivery methods of hepatic stem cells in liver regeneration, and discusses some challenges for their therapeutic application.

关键词： stem cell     liver disease     regenerative medicine    

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标题 作者 时间 类型 操作

Regulatory factors of mesenchymal stem cell migration into injured tissues and their signal transduction

null

期刊论文

Epithelial-to-mesenchymal transition in cancer: complexity and opportunities

Yun Zhang, Robert A. Weinberg

期刊论文

Cell therapy for the treatment of reproductive diseases and infertility: an overview from the mechanism

期刊论文

Umbilical cord-derived mesenchymal stem cells: strategies, challenges, and potential for cutaneous regeneration

null

期刊论文

Immunohistochemical characterization of hepatic stem cell-related cells in developing human liver

XU Jun, HU Yong, WANG Jian, ZHANG Taiping, ZHOU Ji, YU Hongyu

期刊论文

Extracellular vesicle-carried GTF2I from mesenchymal stem cells promotes the expression of tumor-suppressive

期刊论文

Mesenchymal stem cells and immune disorders: from basic science to clinical transition

Shihua Wang, Rongjia Zhu, Hongling Li, Jing Li, Qin Han, Robert Chunhua Zhao

期刊论文

Clinical study using mesenchymal stem cells for the treatment of patients with severe COVID-19

Lingling Tang, Yingan Jiang, Mengfei Zhu, Lijun Chen, Xiaoyang Zhou, Chenliang Zhou, Peng Ye, Xiaobei Chen, Baohong Wang, Zhenyu Xu, Qiang Zhang, Xiaowei Xu, Hainv Gao, Xiaojun Wu, Dong Li, Wanli Jiang, Jingjing Qu, Charlie Xiang, Lanjuan Li

期刊论文

Mesenchymal stem cells hold promise for regenerative medicine

Shihua Wang, Xuebin Qu, Robert Chunhua Zhao

期刊论文

Implantation of human umbilical cord mesenchymal stem cells for ischemic stroke: perspectives and challenges

null

期刊论文

Capacity of human umbilical cord-derived mesenchymal stem cells to differentiate into sweat gland-like

null

期刊论文

Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study

null

期刊论文

The unregulated commercialization of stem cell treatments: a global perspective

Douglas Sipp

期刊论文

The regulatory sciences for stem cell-based medicinal products

null

期刊论文

Therapeutic potential of stem cell in liver regeneration

null

期刊论文