分子影像监测血管内皮细胞生长因子预处理促进体外和体内脂肪间充质干细胞存活与增殖的研究

干细胞疗法为缺血性心血管病的组织再生带来希望,然而体内移植后干细胞的不良转归严重制约了其治疗效果.研究表明,血管内皮细胞生长因子(vascular endotllelial growth factor,VEGF)或可对干细胞产生保护作用;同时,分子影像可作为干细胞研究的有力手段,实现体内外干细胞生物学过程的可视化与实时...     

Menstrual blood stem cells as a potential source for cell therapy

Cell replacement and restorative therapies show great promise for the treatment of various diseases and traumas. Various types of stem cells that are rather different in terms of biological properties are evaluated as potential sources for cell therapy. Mesenchymal stem cells (MSCs) display relatively high proliferative activity and high level of plasticity and can be differentiated not only into cells of mesenchymal lineage, but also neurons. Among the MSC populations, the population of endometrial stem cells, including that present in the menstrual blood, is readily available. In the current review, we analyze the biological properties of the menstrual blood stem cells and the possibilities of using them as a potential source for cell therapy.     

Novel insights in basic and applied stem cell therapy

The achievement of novel findings in stem cell research were the subject of the meeting organized by Stem Cell Research Italy (SCR Italy) and by the International Society for Cellular Therapy-Europe (ISCT). Stem cell therapy represents great promise for the future of molecular and regenerative medicine. The use of several types of stem cells is a real opportunity to provide a valid approach to curing several untreatable human diseases. Before it is suitable for clinical applications, stem cell biology needs to be investigated further and in greater detail. Basic stem cell research could provide exact knowledge regarding stem cell action mechanisms, and pre-clinical research on stem cells on an in vivo model of disease provides scientific evidence for future human applications. Applied stem cell research is a promising new approach to handling several diseases. Along with tissue engineering, it offers a new and promising discipline that can help to manage human pathologies through stem cell therapy. All of these themes were discussed in this meeting, covering stem cell subtypes with their newest basic and applied research.     

Research status and prospect of stem cells in the treatment of diabetes mellitus

Beta cell mass and function are decreased to varying degrees in diabetes. Islet cell replacement or regenerative therapy may offer great therapeutic promise to people with diabetes. In addition to primary pancreatic β cells, recent studies on regeneration of functional insulin producing cells (IPCs) revealed that several alternative cell sources, including embryonic stem cells, induced pluripotent stem cells and adult stem cells, can generate IPCs by differentiation, reprogramming, and trans-differentiation. In this review, we discuss stem cells as a potential alternative cell source for the treatment of diabetes.     

Adult stem cells for cardiac repair: a choice between skeletal myoblasts and bone marrow stem cells

The real promise of a stem cell-based approach for cardiac regeneration and repair lies in the promotion of myogenesis and angiogenesis at the site of the cell graft to achieve both structural and functional benefits. Despite all of the progress and promise in this field, many unanswered questions remain; the answers to these questions will provide the much-needed breakthrough to harness the real benefits of cell therapy for the heart in the clinical perspective. One of the major issues is the choice of donor cell type for transplantation. Multiple cell types with varying potentials have been assessed for their ability to repopulate the infarcted myocardium; however, only the adult stem cells, that is, skeletal myoblasts (SkM) and bone marrow-derived stem cells (BMC), have been translated from the laboratory bench to clinical use. Which of these two cell types will provide the best option for clinical application in heart cell therapy remains arguable. With results pouring in from the long-term follow-ups of previously conducted phase I clinical studies, and with the onset of phase II clinical trials involving larger population of patients, transplantation of stem cells as a sole therapy without an adjunct conventional revascularization procedure will provide a deeper insight into the effectiveness of this approach. The present article discusses the pros and cons of using SkM and BMC individually or in combination for cardiac repair, and critically analyzes the progress made with each cell type.     

Carbon Quantum Dots as Multi-Purpose Nanomaterial in Stem Cell Therapy

During stem cell therapy, some issues, such as obscure fate of stem cells or their low survival rate in the body, should be addressed to boost their therapeutic efficiency. Nanotechnology offers a suitable solution to combat such limitations. Carbon quantum dots (CQDs) are carbon-based nanomaterials and may be used as multi-purpose compounds in stem cell therapy. CQDs are excellent choices for stem cell labeling thanks to their special features such as optical properties and good biocompatibility. Besides, they can modulate the biological function of stem cells, such as their proliferation, homing ability, and differentiation properties. Considering the charismatic feature of CQDs and their broad unique effect on stem cells, the current review aims to summarize the most advancements in this field. Hence, we first focused on CQDs synthesis and their applications. In the next section, the stem cell categories will be discussed, and the final part is dedicated to the recent research evaluating the impact of CQDs on stem cell therapy.     

Comparative capability of menstrual blood versus bone marrow derived stem cells in neural differentiation

In order to characterize the potency of menstrual blood stem cells (MenSCs) for future cell therapy of neurological disorders instead of bone marrow stem cells (BMSCs) as a well-known and conventional source of adult stem cells, we examined the in vitro differentiation potential of these stem cells into neural-like cells. The differentiation potential of MenSCs to neural cells in comparison with BMSCs was assessed under two step neural differentiation including conversion to neurosphere-like cells and final differentiation. The expression levels of Nestin, Microtubule-associated protein 2, gamma-aminobutyric acid type B receptor subunit 1 and 2, and Tubulin, beta 3 class III mRNA and/or protein were up-regulated during development of MenSCs into neurosphere-like cells (NSCs) and neural-like cells. The up-regulation level of these markers in differentiated neural-like cells from MenSCs was comparable with differentiated cells from BMSCs. Moreover, both differentiated MenSCs and BMSCs expressed high levels of potassium, calcium and sodium channel genes developing functional channels with electrophysiological recording. For the first time, we demonstrated that MenSCs are a unique cell population with differentiation ability into neural-like cells comparable to BMSCs. In addition, we have introduced an approach to generate NSCs from MenSCs and BMSCs and their further differentiation into neural-like cells in vitro. Our results hold a promise to future stem cell therapy of neurological disorders using NSCs derived from menstrual blood, an accessible source in every woman.     

Potential adenovirus-mediated gene therapy of glioma cancer

Malignant gliomas are typically characterized by rapid cell proliferation and a marked propensity to invade and damage surrounding tissues. They are the main brain tumors notoriously resistant to currently available therapies, since they fail to undergo apoptosis upon anticancer treatments. With recent advances in neuroscience and improved understanding of the molecular mechanisms of invasive migration, gene therapy provides a new strategy for treating glioma cancer. Brain tumor gene therapy using viral vectors and stem cells has shown promise in animal model and human patient studies. Here, we review recent studies on engineering adenoviral vectors that can be used as therapy for brain tumors. The new findings presented in this study are essential for the further exploration of this cancer and they represent an approach for developing a newer and more effective therapeutic approach in the clinical treatment of human glioma cancer.     

Stem Cell Therapy: A New Therapeutic Option for Cardiovascular Diseases

Cardiovascular diseases are known as one of major causes of morbidity and mortality worldwide. Despite the many advancement in therapies are associated with cardiovascular diseases, it seems that finding of new therapeutic option is necessary. Cell therapy is one of attractive therapeutic platforms for treatment of a variety of diseases such as cardiovascular diseases. Among of various types of cell therapy, stem cell therapy has been emerged as an effective therapeutic approach in this area. Stem cells divided into multipotent stem cells and pluripotent stem cells. A large number studies indicated that utilization of each of them are associated with a variety of advantages and disadvantages. Multiple lines evidence indicated that stem cell therapy could be used as suitable therapeutic approach for treatment of cardiovascular diseases. Many clinical trials have been performed for assessing efficiency of stem cell therapies in human. However, stem cell therapy are associated with some challenges, but, it seems resolving of them could contribute to using of them as effective therapeutic approach for patients who suffering from cardiovascular diseases. In the current review, we summarized current therapeutic strategies based on stem cells for cardiovascular diseases. J. Cell. Biochem. 119: 95–104, 2018. © 2017 Wiley Periodicals, Inc.     

Direct reprogramming of Sertoli cells into multipotent neural stem cells by defined factors

Multipotent neural stem/progenitor cells hold great promise for cell therapy. The reprogramming of fibroblasts to induced pluripotent stem cells as well as mature neurons suggests a possibility to convert a terminally differentiated somatic cell into a multipotent state without first establishing pluripotency. Here, we demonstrate that Sertoli cells derived from mesoderm can be directly converted into a multipotent state that possesses neural stem/progenitor cell properties. The induced neural stem/progenitor cells (iNSCs) express multiple NSC-specific markers, exhibit a global gene-expression profile similar to normal NSCs, and are capable of self-renewal and differentiating into glia and electrophysiologically functional neurons. iNSC-derived neurons stain positive for tyrosine hydroxylase (TH), γ-aminobutyric acid, and choline acetyltransferase. In addition, iNSCs can survive and generate synapses following transplantation into the dentate gyrus. Generation of iNSCs may have important implications for disease modeling and regenerative medicine.     

Turning straw into gold: directing cell fate for regenerative medicine

Regenerative medicine offers the hope that cells for disease research and therapy might be created from readily available sources. To fulfil this promise, the cells available need to be converted into the desired cell types. We review two main approaches to accomplishing this goal: in vitro directed differentiation, which is used to push pluripotent stem cells, including embryonic stem cells or induced pluripotent stem cells, through steps similar to those that occur during embryonic development; and reprogramming (also known as transdifferentiation), in which a differentiated cell is converted directly into the cell of interest without proceeding through a pluripotent intermediate. We analyse the status of progress made using these strategies and highlight challenges that must be overcome to achieve the goal of cell-replacement therapy.     

Investigating the mincing method for isolation of adipose-derived stem cells from pregnant women fat

The success of stem cell application in regenerative medicine, usually require a stable source of stem or progenitor cells. Fat tissue represents a good source of stem cells because it is rich in stem cells and there are fewer ethical issues related to the use of such stem cells, unlike embryonic stem cells. Therefore, there has been increased interest in adipose-derived stem cells (ADSCs) for tissue engineering applications. Here, we aim to provide an easy processing method for isolating adult stem cells from human adipose tissue harvested from the subcutaneous fat of the abdominal wall during gynecologic surgery. We used a homogenizer to mince fat and compared the results with those obtained from the traditional cut method involving a sterile scalpel and forceps. Our results showed that our method provides another stable and quality source of stem cells that could be used in cases with a large quantity of fat. Furthermore, we found that pregnancy adipose-derived stem cells (P-ADSCs) could be maintained in vitro for extended periods with a stable population doubling and low senescence levels. P-ADSCs could also differentiate in vitro into adipogenic, osteogenic, chondrogenic, and insulin-producing cells in the presence of lineage-specific induction factors. In conclusion, like human lipoaspirates, adipose tissues obtained from pregnant women contain multipotent cells with better proliferation and showed great promise for use in both stem cell banking studies as well as in stem cell therapy.     

Cardiac cell therapy: pre-conditioning effects in cell-delivery strategies

Stem-cell therapy holds great promise for the treatment of ischemic heart disease. However, the benefit of cardiac cell therapy has not yet been proven in long-term clinical trials. Poor engraftment and survival of transplanted cells is one of the major concerns for the successful application of stem cells in cardiac cell therapy. Cell and cardiac pre-conditioning are now being explored as new approaches to support cell survival and enhance the therapeutic efficacy. In this paper, we summarize the state-of-the-art methods of cell delivery and cell survival post-delivery, with a focus on the pre-conditioning approaches that have been attempted to support the survival of transplanted cells.     

Adult neural stem cells: response to stroke injury and potential for therapeutic applications

The plasticity of neural stem/progenitor cells allows a variety of different responses to many environmental cues. In the past decade, significant research has gone into understanding the regulation of neural stem/progenitor cell properties, because of their promise for cell replacement therapies in adult neurological diseases. Both endogenous and grafted neural stem/progenitor cells are known to have the ability to migrate long distances to lesioned sites after brain injury and differentiate into new neurons. Several chemokines and growth factors, including stromal cell-derived factor-1 and vascular endothelial growth factor, have been shown to stimulate the proliferation, differentiation, and migration of neural stem/progenitor cells, and investigators have now begun to identify the critical downstream effectors and signaling mechanisms that regulate these processes. Both our own lab and others have shown that the extracellular matrix and matrix remodeling factors play a critical role in directing cell differentiation and migration of adult neural stem/progenitor cells within injured sites. Identification of these and other molecular pathways involved in stem cell homing into ischemic areas is vital for the development of new treatments. To ensure the best functional recovery, regenerative therapy may require the application of a combination approach that includes cell replacement, trophic support, and neural protection. Here we review the current state of our knowledge about endogenous adult and exogenous neural stem/progenitor cells as potential therapeutic agents for central nervous system injuries.     

帕金森病的细胞治疗研究进展

干细胞为治疗帕金森病提供了新的希望.目前用于研究的干细胞主要有神经干细胞、胚胎干细胞、诱导多功能干细胞、间充质干细胞等.本文回顾了上述细胞在移植治疗帕金森病研究中的进展,并介绍了近期出现的将体细胞直接重编程为神经细胞或神经干细胞的新技术.     

Unraveling the molecular components and genetic blueprints of stem cells

Remarkable progress in stem cell biology research over the past few years has provoked a promise for the future of tissue regeneration and gene therapies; so much so, that the use of stem cells in clinical therapy seemed to be just around the corner. However, we now realize there is still a huge task before us to improve our understanding of the nature of stem cells before utilizing them to benefit human health. Stem cell behavior is determined by specific gene products; thus, unraveling the molecular components and genetic blueprints of stem cells will provide important insight into understanding stem cell properties. Here we summarize the research of various groups using microarray technology and other approaches to determine the gene expression profiles in stem cells, particularly in hematopoietic stem cells (HSCs). These works have, to a certain degree, helped to narrow down the candidate genes predominantly expressed in HSCs, revealed a list of stemness genes, and indirectly demonstrated the wide-open chromatin state of stem cells and, with it, the molecular basis of the multipotentiality of stem cells.     

Tissue engineering with muscle-derived stem cells

Tissue engineering and cell therapy approaches aim to take advantage of the repopulating ability and plasticity of multipotent stem cells to regenerate lost or diseased tissue. Researchers continue to investigate stem cells in mature tissues and demonstrate the potential ability of organ-specific cells to differentiate into multiple lineages. One stem cell that displays such promise is the muscle-derived stem cell (MDSC). Data supporting the existence of MDSCs have emerged as part of investigations to improve myoblast cell transplantation for the treatment of muscular dystrophies. As these efforts continue, the potential for MDSC-based therapy for other musculoskeletal injuries, as well as for cardiac and smooth muscle injuries, is currently being explored.     

Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5⁺ stem cell

Adult stem-cell therapy holds promise for the treatment of gastrointestinal diseases. Here we describe methods for long-term expansion of colonic stem cells positive for leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5(+) cells) in culture. To test the transplantability of these cells, we reintroduced cultured GFP(+) colon organoids into superficially damaged mouse colon. The transplanted donor cells readily integrated into the mouse colon, covering the area that lacked epithelium as a result of the introduced damage in recipient mice. At 4 weeks after transplantation, the donor-derived cells constituted a single-layered epithelium, which formed self-renewing crypts that were functionally and histologically normal. Moreover, we observed long-term (>6 months) engraftment with transplantation of organoids derived from a single Lgr5(+) colon stem cell after extensive in vitro expansion. These data show the feasibility of colon stem-cell therapy based on the in vitro expansion of a single adult colonic stem cell.     

Optimizing stem cells for cardiac repair: Current status and new frontiers in regenerative cardiology

Cell therapy has the potential to improve healing of ischemic heart, repopulate injured myocardium and restore cardiac function. The tremendous hope and potential of stem cell therapy is well understood, yet recent trials involving cell therapy for cardiovascular diseases have yielded mixed results with inconsistent data thereby readdressing controversies and unresolved questions regarding stem cell efficacy for ischemic cardiac disease treatment. These controversies are believed to arise by the lack of uniformity of the clinical trial methodologies, uncertainty regarding the underlying reparative mechanisms of stem cells, questions concerning the most appropriate cell population to use, the proper delivery method and timing in relation to the moment of infarction, as well as the poor stem cell survival and engraftment especially in a diseased microenvironment which is collectively acknowledged as a major hindrance to any form of cell therapy. Indeed, the microenvironment of the failing heart exhibits pathological hypoxic, oxidative and inflammatory stressors impairing the survival of transplanted cells. Therefore, in order to observe any significant therapeutic benefit there is a need to increase resilience of stem cells to death in the transplant microenvironment while preserving or better yet improving their reparative functionality. Although stem cell differentiation into cardiomyocytes has been observed in some instance, the prevailing reparative benefits are afforded through paracrine mechanisms that promote angiogenesis, cell survival, transdifferentiate host cells and modulate immune responses. Therefore, to maximize their reparative functionality, ex vivo manipulation of stem cells through physical, genetic and pharmacological means have shown promise to enable cells to thrive in the postischemic transplant microenvironment. In the present work, we will overview the current status of stem cell therapy for ischemic heart disease, discuss the most recurring cell populations employed, the mechanisms by which stem cells deliver a therapeutic benefit andstrategies that have been used to optimize and increase survival and functionality of stem cells including ex vivo preconditioning with drugs and a novel "pharmacooptimizer" as well as genetic modifications.