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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    

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    

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    

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    

Atypical pituitary hormone–target tissue axis

《医学前沿(英文)》 2023年 第17卷 第1期   页码 1-17 doi: 10.1007/s11684-022-0973-7

摘要: A long-held belief is that pituitary hormones bind to their cognate receptors in classical target glands to actuate their manifold functions. However, a number of studies have shown that multiple types of pituitary hormone receptors are widely expressed in non-classical target organs. Each pituitary gland-derived hormone exhibits a wide range of nonconventional biological effects in these non-classical target organs. Herein, the extra biological functions of pituitary hormones, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, adrenocorticotrophic hormone, and prolactin when they act on non-classical organs were summarized, defined by the novel concept of an “atypical pituitary hormone–target tissue axis.” This novel proposal explains the pathomechanisms of abnormal glucose and lipid metabolism, obesity, hypertension, fatty liver, and atherosclerosis while offering a more comprehensive and systematic insights into the coordinated regulation of environmental factors, genetic factors, and neuroendocrine hormones on human biological functions. The continued exploration of the physiology of the “atypical pituitary hormone–target tissue axis” could enable the identification of novel therapeutic targets for metabolic diseases.

关键词: thyroid-stimulating hormone     follicle-stimulating hormone     luteinizing hormone     adrenocorticotrophic hormone     prolactin    

Progress and perspectives of neural tissue engineering

null

《医学前沿(英文)》 2015年 第9卷 第4期   页码 401-411 doi: 10.1007/s11684-015-0415-x

摘要:

Traumatic injuries to the nervous system lead to a common clinical problem with a quite high incidence and affect the patient’s quality of life. Based on a major challenge not yet addressed by current therapeutic interventions for these diseases, a novel promising field of neural tissue engineering has emerged, grown, and attracted increasing interest. This review provides a brief summary of the recent progress in the field, especially in combination with the research experience of the author’s group. Several important aspects related to tissue engineered nerves, including the theory on their construction, translation into the clinic, improvements in fabrication technologies, and the formation of a regenerative environment, are delineated and discussed. Furthermore, potential research directions for the future development of neural tissue engineering are suggested.

关键词: nerve injury     tissue engineering     nerve grafts    

The stem cell and tissue engineering research in Chinese ophthalmology

GE Jian, LIU Jingbo

《医学前沿(英文)》 2007年 第1卷 第1期   页码 6-10 doi: 10.1007/s11684-007-0002-x

摘要: Much has been considerably developed recently in the ophthalmic research of stem cell (SC) and tissue engineering (TE). They have become closer to the clinical practice, standardized and observable. Leading edge research of SC and TE on the ocular surface reconstruction, neuroregeneration and protection, and natural animal model has become increasingly available. However, challenges remain on the way, especially on the aspects of function reconstruction and specific differentiation. This paper reviews the new developments in this area with an intention of identifying research priorities for the future.

关键词: available     observable     neuroregeneration     protection     function reconstruction    

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    

Decellularized extracellular matrix mediates tissue construction and regeneration

《医学前沿(英文)》 2022年 第16卷 第1期   页码 56-82 doi: 10.1007/s11684-021-0900-3

摘要: Contributing to organ formation and tissue regeneration, extracellular matrix (ECM) constituents provide tissue with three-dimensional (3D) structural integrity and cellular-function regulation. Containing the crucial traits of the cellular microenvironment, ECM substitutes mediate cell–matrix interactions to prompt stem-cell proliferation and differentiation for 3D organoid construction in vitro or tissue regeneration in vivo. However, these ECMs are often applied generically and have yet to be extensively developed for specific cell types in 3D cultures. Cultured cells also produce rich ECM, particularly stromal cells. Cellular ECM improves 3D culture development in vitro and tissue remodeling during wound healing after implantation into the host as well. Gaining better insight into ECM derived from either tissue or cells that regulate 3D tissue reconstruction or organ regeneration helps us to select, produce, and implant the most suitable ECM and thus promote 3D organoid culture and tissue remodeling for in vivo regeneration. Overall, the decellularization methodologies and tissue/cell-derived ECM as scaffolds or cellular-growth supplements used in cell propagation and differentiation for 3D tissue culture in vitro are discussed. Moreover, current preclinical applications by which ECM components modulate the wound-healing process are reviewed.

关键词: decellularized extracellular matrix     3D culture     organoids     tissue repair    

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

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    

Non-closure of the peritoneum and subcutaneous tissue at radical hysterectomy: A randomized controlled

Zhou-Fang XIONG MD, Wei-Hong DONG MD, Ze-Hua WANG MD,

《医学前沿(英文)》 2010年 第4卷 第1期   页码 112-116 doi: 10.1007/s11684-010-0016-7

摘要: We conducted a trial to assess the influence of closure or nonclosure of the peritoneum and subcutaneous tissue on the clinical outcomes of cervical cancer patients who underwent radical hysterectomy with lower abdominal cross incision. This randomized controlled trial was performed on 158 cervical cancer patients in our hospital between January 2002 and June 2004. Eighty-two patients were allocated to the “closure” group and 76 patients to the “nonclosure” group. Results showed that non-closure of the peritoneum and subcutaneous tissue could shorten operation time and febrile duration, reduce antibiotics requirement, increase the volume of drainage and decrease the incidence of liquefaction of subcutaneous fat (<0.05). There was no difference in blood loss, postoperative complications, bowel function restoration and post-operative stay between the two groups (>0.05). Our study revealed that closure of the peritoneum and subcutaneous tissue provides no immediate postoperative benefits while unnecessarily lengthening surgical time and anesthesia exposure. The practice of closure of the peritoneum and subcutaneous tissue at radical hysterectomy should be questioned.

关键词: cervical cancer     radical surgery     peritoneum     subcutaneous tissue    

Primary cilia in hard tissue development and diseases

《医学前沿(英文)》 2021年 第15卷 第5期   页码 657-678 doi: 10.1007/s11684-021-0829-6

摘要: Bone and teeth are hard tissues. Hard tissue diseases have a serious effect on human survival and quality of life. Primary cilia are protrusions on the surfaces of cells. As antennas, they are distributed on the membrane surfaces of almost all mammalian cell types and participate in the development of organs and the maintenance of homeostasis. Mutations in cilium-related genes result in a variety of developmental and even lethal diseases. Patients with multiple ciliary gene mutations present overt changes in the skeletal system, suggesting that primary cilia are involved in hard tissue development and reconstruction. Furthermore, primary cilia act as sensors of external stimuli and regulate bone homeostasis. Specifically, substances are trafficked through primary cilia by intraflagellar transport, which affects key signaling pathways during hard tissue development. In this review, we summarize the roles of primary cilia in long bone development and remodeling from two perspectives: primary cilia signaling and sensory mechanisms. In addition, the cilium-related diseases of hard tissue and the manifestations of mutant cilia in the skeleton and teeth are described. We believe that all the findings will help with the intervention and treatment of related hard tissue genetic diseases.

关键词: primary cilia     bone     mechanical sensing     hard tissue     cilium-related bone disease     tooth    

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    

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    

Stem cell niches and endogenous electric fields in tissue repair

null

《医学前沿(英文)》 2011年 第5卷 第1期   页码 40-44 doi: 10.1007/s11684-011-0108-z

摘要:

Adult stem cells are responsible for homeostasis and repair of many tissues. Endogenous adult stem cells reside in certain regions of organs, known as the stem cell niche, which is recognized to have an important role in regulating tissue maintenance and repair. In wound healing and tissue repair, stem cells are mobilized and recruited to the site of wound, and participate in the repair process. Many regulatory factors are involved in the stem cell-based repair process, including stem cell niches and endogenous wound electric fields, which are present at wound tissues and proved to be important in guiding wound healing. Here we briefly review the role of stem cell niches and endogenous electric fields in tissue repair, and hypothesize that endogenous electric fields become part of stem cell niche in the wound site.

关键词: stem cell     stem cell niche     electric field     tissue repair    

标题 作者 时间 类型 操作

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

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

Yun Zhang, Robert A. Weinberg

期刊论文

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

null

期刊论文

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

null

期刊论文

Atypical pituitary hormone–target tissue axis

期刊论文

Progress and perspectives of neural tissue engineering

null

期刊论文

The stem cell and tissue engineering research in Chinese ophthalmology

GE Jian, LIU Jingbo

期刊论文

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

null

期刊论文

Decellularized extracellular matrix mediates tissue construction and regeneration

期刊论文

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

null

期刊论文

Non-closure of the peritoneum and subcutaneous tissue at radical hysterectomy: A randomized controlled

Zhou-Fang XIONG MD, Wei-Hong DONG MD, Ze-Hua WANG MD,

期刊论文

Primary cilia in hard tissue development and diseases

期刊论文

Mesenchymal stem cells hold promise for regenerative medicine

Shihua Wang, Xuebin Qu, Robert Chunhua Zhao

期刊论文

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

null

期刊论文

Stem cell niches and endogenous electric fields in tissue repair

null

期刊论文