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Human menstrual blood-derived stem cells alleviate autoimmune hepatitis via JNK/MAPK signaling pathway

《医学前沿（英文）》 2023年 第17卷 第3期   页码 534-548 doi: 10.1007/s11684-022-0953-y

摘要： Autoimmune hepatitis (AIH) is a severe globally distributed liver disease that could occur at any age. Human menstrual blood-derived stem cells (MenSCs) have shown therapeutic effect in acute lung injury and liver failure. However, their role in the curative effect of AIH remains unclear. Here, a classic AIH mouse model was constructed through intravenous injection with concanavalin A (Con A). MenSCs were intravenously injected while Con A injection in the treatment groups. The results showed that the mortality by Con A injection was significantly decreased by MenSCs treatment and liver function tests and histological analysis were also ameliorated. The results of phosphoproteomic analysis and RNA-seq revealed that MenSCs improved AIH, mainly by apoptosis and c-Jun N-terminal kinase/mitogen-activated protein signaling pathways. Apoptosis analysis demonstrated that the protein expression of cleaved caspase 3 was increased by Con A injection and reduced by MenSCs transplantation, consistent with the TUNEL staining results. An AML12 co-culture system and JNK inhibitor (SP600125) were used to verify the JNK/MAPK and apoptosis signaling pathways. These findings suggested that MenSCs could be a promising strategy for AIH.

关键词： autoimmune hepatitis (AIH)     concanavalin A (Con A)     human menstrual blood-derived stem cells (MenSCs)     apoptosis     mitogen-activated protein kinase (MAPK)    

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Capacity of human umbilical cord-derived mesenchymal stem cells to differentiate into sweat gland-likecells: a preclinical study

null

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

null

《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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Intracellular trehalose improves the survival of human red blood cells by freeze-drying

HE Hui, LIU Baolin, HUA Zezhao, LI Chuan, WU Zhengzheng

《能源前沿（英文）》 2007年 第1卷 第1期   页码 120-124 doi: 10.1007/s11708-007-0014-x

摘要： Freeze-drying of human red blood cells has a potential important application for blood transfusion. The aim of this study was to investigate the effects of intracellular trehalose on the survival of red blood cells after freeze-drying and rehydration. Fresh red blood cells were incubated in trehalose solutions of various concentrations at 37vH for 7 h following freeze-drying. Polyvinylpyrrolidone, Trehalose, sodium citrate, and human serum albumin were used as extracellular protective agents for the freeze-drying of red blood cells. The results indicated that the intracellular trehalose concentration was increased with increasing concentration of extracellular trehalose solution, and the maximum concentration of intracellular trehalose reached 35 mmol/L. The viability of freeze-dried red blood cells increased with the increment of intracellular trehalose concentration.
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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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Evidence for lung repair and regeneration in humans: key stem cells and therapeutic functions of fibroblast

Xuran Chu, Chengshui Chen, Chaolei Chen, Jin-San Zhang, Saverio Bellusci, Xiaokun Li

《医学前沿（英文）》 2020年 第14卷 第3期   页码 262-272 doi: 10.1007/s11684-019-0717-5

摘要： Regeneration carries the idea of regrowing partially or completely a missing organ. Repair, on the other hand, allows restoring the function of an existing but failing organ. The recognition that human lungs can both repair and regenerate is quite novel, the concept has not been widely used to treat patients. We present evidence that the human adult lung does repair and regenerate and introduce different ways to harness this power. Various types of lung stem cells are capable of proliferating and differentiating upon injury driving the repair/regeneration process. Injury models, primarily in mice, combined with lineage tracing studies, have allowed the identification of these important cells. Some of these cells, such as basal cells, broncho-alveolar stem cells, and alveolar type 2 cells, rely on fibroblast growth factor (FGF) signaling for their survival, proliferation and/or differentiation. While pre-clinical studies have shown the therapeutic benefits of FGFs, a recent clinical trial for acute respiratory distress syndrome (ARDS) using intravenous injection of FGF7 did not report the expected beneficial effects. We discuss the potential reasons for these negative results and propose the rationale for new approaches for future clinical trials, such as delivery of FGFs to the damaged lungs through efficient inhalation systems, which may be more promising than systemic exposure to FGFs. While this change in the administration route presents a challenge, the therapeutic promises displayed by FGFs are worth the effort.

关键词： FGF     human lung     repair     regeneration     stem cells    

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Pluripotent stem cells exhibiting similar characteristics can be isolated from human fetal bone marrow

FANG Baijun, SONG Yongping, LIN Quande, ZHAO Chunhua, SHI Mingxia

《医学前沿（英文）》 2007年 第1卷 第2期   页码 185-191 doi: 10.1007/s11684-007-0035-1

摘要： Previously, we reported that a cell population derived from human fetal bone marrow (BM), termed here Flk1CD34 postembryonic pluripotent stem cells (PPSCs) that have the characteristics of mesenchymal stem cells (MSCs), could differentiate into ectodermal, endodermal and mesodermal cell types at the single cell level , and that these cells could also differentiate into the epithelium of liver, lung, gut, as well as the hematopoietic and endothelial lineages after transplantion into irradiated non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. In this study, we further isolated pluripotent stem cells from human fetal heart, liver, muscle, lung, derma, kidney, and fat and then analyzed the characteristics and function of these stem cells. It was found that the phenotype of the culture-expanded pluripotent stem cells from different fetal tissues was similar to BM-derived Flk1CD34 PPSCs, i.e. Flk1 and CD44 positive, GlyA, CD34, CD45, class I-HLA and HLA-DR negative. Morphologically, these cells were fibroblast-like and the doubling time was about 30 h. More importantly, culture-expanded pluripotent stem cells from all these fetal tissues were able to differentiate into cells with morphologic and phenotypic characteristics of adipocytes, osteocytes, neurons, glial cells and hepatocytes. These pluripotent stem cells with characteristics similar to fetal BM-derived Flk1CD34 PPSCs can be selected and cultured from tissues other than the BM. This phenomenon may help explain the stem cell plasticity found in multiple human tissues. In addition, as fetal BM-derived Flk1CD34 PPSCs, these pluripotent stem cells from different fetal tissues had the capacity for self-renewal and multi-lineage differentiation even after being expanded for more than 40 population doublings . Thus, they may be an ideal source of stem cells for treatment of inherited or degenerative diseases.

关键词： endothelial     phenomenon     ectodermal     Flk1CD34 postembryonic     irradiated non-obese    

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Determination of telomerase activity in stem cells and non-stem cells of breast cancer

LI Zhi, HE Yanli, ZHANG Jiahua, ZHANG Jinghui, HUANG Tao

《医学前沿（英文）》 2007年 第1卷 第3期   页码 294-298 doi: 10.1007/s11684-007-0056-9

摘要： Although all normal tissue cells, including stem cells, are genetically homologous, variation in gene expression patterns has already determined the distinct roles for individual cells in the physiological process due to the occurrence of epigenetic modification. This is of special importance for the existence of tissue stem cells because they are exclusively immortal within the body, capable of selfreplicating and differentiating by which tissues renew and repair itself and the total tissue cell population maintains a steady-state. Impairment of tissue stem cells is usually accompanied by a reduction in cell number, slows down the repair process and causes hypofunction. For instance, chemotherapy usually leads to depression of bone marrow and hair loss. Cellular aging is closely associated with the continuous erosion of the telomere while activation of telomerase repairs and maintains telomeres, thus slowing the aging process and prolonging cell life. In normal adults, telomerase activation mainly presents in tissue stem cells and progenitor cells giving them unlimited growth potential. Despite the extensive demonstration of telomerase activation in malignancy (>80%), scientists found that heterogeneity also exists among the tumor cells and only minorities of cells, designated as cancer stem cells, undergo processes analogous to the self-renewal and differentiation of normal stem cells while the rest have limited lifespans. In this study, telomerase activity was measured and compared in breast cancer stem cells and non-stem cells that were phenotypically sorted by examining surface marker expression. The results indicated that cancer stem cells show a higher level of enzyme activity than non-stem cells. In addition, associated with the repair of cancer tissue (or relapse) after chemotherapy, telomerase activity in stem cells was markedly increased.
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Porcine pluripotent stem cells: progress, challenges and prospects

Jianyong HAN, Yi-Liang MIAO, Jinlian HUA, Yan LI, Xue ZHANG, Jilong ZHOU, Na LI, Ying ZHANG, Jinying ZHANG, Zhonghua LIU

《农业科学与工程前沿（英文）》 2019年 第6卷 第1期   页码 8-27 doi: 10.15302/J-FASE-2018233

摘要：

Pluripotent stem cells (PSCs) are characterized by their capacity for high self-renewal and multiple differentiation potential and include embryonic stem cells, embryonic germ cells and induced PSCs. PSCs provide a very suitable model for the studies of human diseases, drugs screening, regenerative medicine and developmental biology research. Pigs are considered as an ideal model for preclinical development of human xenotransplantation, therapeutic approaches and regenerative medicine because of their size and physiological similarity to humans. However, lack of knowledge about the derivation, characterization and pluripotency mechanisms of porcine PSCs hinders progress in these biotechnologies. In this review, we discuss the latest progress on porcine PSCs generation, evaluation criteria for pluripotency, the scientific and technical questions arising from these studies. We also introduce our perspectives on porcine PSC research, in the hope of providing new ideas for generating naive porcine PSCs and animal breeding.

关键词： embryonic germ cells     embryonic stem cells     induced pluripotent stem cells     pigs     pluripotent stem cells    

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The past, present and future of bovine pluripotent stem cells: a brief overview

Xiuchun TIAN

《农业科学与工程前沿（英文）》 2019年 第6卷 第1期   页码 3-7 doi: 10.15302/J-FASE-2018247

摘要：

Although the pursuit of bovine embryonic stem cells started more than 26 years ago for the purpose of gene-targeting, true pluripotent stem cells in this economically important species are still elusive. With the rapid advances in genome-editing and cloning using homologously recombined somatic cells, the need for pluripotent stem cells for precise genetic modification in any species became questionable. With the pig being the better model for human regenerative biology, the identification of the commonalities and uniqueness of the pluripotency circuitry across mammalian species may be the main objective for studying pluripotent stem cells in the bovine.

关键词： bovine     embryonic     induced     pluripotent stem cells    

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Recent advances in myeloid-derived suppressor cell biology

Mahmoud Mohammad Yaseen, Nizar Mohammad Abuharfeil, Homa Darmani, Ammar Daoud

《医学前沿（英文）》 2021年 第15卷 第2期   页码 232-251 doi: 10.1007/s11684-020-0797-2

摘要： In recent years, studying the role of myeloid-derived suppressor cells (MDSCs) in many pathological inflammatory conditions has become a very active research area. Although the role of MDSCs in cancer is relatively well established, their role in non-cancerous pathological conditions remains in its infancy resulting in much confusion. Our objectives in this review are to address some recent advances in MDSC research in order to minimize such confusion and to provide an insight into their function in the context of other diseases. The following topics will be specifically focused upon: (1) definition and characterization of MDSCs; (2) whether all MDSC populations consist of immature cells; (3) technical issues in MDSC isolation, estimation and characterization; (4) the origin of MDSCs and their anatomical distribution in health and disease; (5) mediators of MDSC expansion and accumulation; (6) factors that determine the expansion of one MDSC population over the other; (7) the Yin and Yang roles of MDSCs. Moreover, the functions of MDSCs will be addressed throughout the text.

关键词： non-human primates (rhesus macaques)     myeloid-derived pro-inflammatory cells (MDPCs)     autoimmune disorders     alloimmune responses     pregnancy     mature MDSCs     multiple sclerosis     Yin-Yang law of MDSCs    

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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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Highlights for special issue on “Large Animal Stem Cells”

Jianyong HAN

《农业科学与工程前沿（英文）》 2019年 第6卷 第1期   页码 1-2 doi: 10.15302/J-FASE-2019251

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标题 作者 时间 类型 操作

Human menstrual blood-derived stem cells alleviate autoimmune hepatitis via JNK/MAPK signaling pathway

期刊论文

Capacity of human umbilical cord-derived mesenchymal stem cells to differentiate into sweat gland-likecells: a preclinical study

null

期刊论文

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

null

期刊论文

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

null

期刊论文

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

null

期刊论文

Intracellular trehalose improves the survival of human red blood cells by freeze-drying

HE Hui, LIU Baolin, HUA Zezhao, LI Chuan, WU Zhengzheng

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

Evidence for lung repair and regeneration in humans: key stem cells and therapeutic functions of fibroblast

Xuran Chu, Chengshui Chen, Chaolei Chen, Jin-San Zhang, Saverio Bellusci, Xiaokun Li

期刊论文

Pluripotent stem cells exhibiting similar characteristics can be isolated from human fetal bone marrow

FANG Baijun, SONG Yongping, LIN Quande, ZHAO Chunhua, SHI Mingxia

期刊论文

Determination of telomerase activity in stem cells and non-stem cells of breast cancer

LI Zhi, HE Yanli, ZHANG Jiahua, ZHANG Jinghui, HUANG Tao

期刊论文

Porcine pluripotent stem cells: progress, challenges and prospects

Jianyong HAN, Yi-Liang MIAO, Jinlian HUA, Yan LI, Xue ZHANG, Jilong ZHOU, Na LI, Ying ZHANG, Jinying ZHANG, Zhonghua LIU

期刊论文

The past, present and future of bovine pluripotent stem cells: a brief overview

Xiuchun TIAN

期刊论文

Recent advances in myeloid-derived suppressor cell biology

Mahmoud Mohammad Yaseen, Nizar Mohammad Abuharfeil, Homa Darmani, Ammar Daoud

期刊论文

Mesenchymal stem cells hold promise for regenerative medicine

Shihua Wang, Xuebin Qu, Robert Chunhua Zhao

期刊论文

Highlights for special issue on “Large Animal Stem Cells”

Jianyong HAN

期刊论文