Stem Cells and Muscle Diseases

In the past recent years, basic science work and initial clinical trials have provided starting evidence that stem cells are of potential value for treatment of certain human diseases, where they could help to regenerate tissues which are defective because of either genetic or acquired diseases. This area represents an emerging field of biomedicine based on a series of new discoveries in the field of stem cell biology and developmental biology that have made possible to isolate and expand stem cells from many human tissues. Additional evidence has also revealed the role of tissue environment that, by releasing a complex mixture of cytokines and growth factors, can influence the recruitment and functional integration of stem cells into specific organs. However, there is an urgent need for more advancement in basic biology of stem cells and related topics, which will be instrumental for the implementation of stem cell-based therapy at the clinical level, as treatment accessibility will depend on the acquisition of sufficient knowledge to develop adequate technologies to produce sufficient cell numbers and to drive their differentiating potentials.     

Hematopoietic stem cells: the paradigmatic tissue-specific stem cell

The recent prospective isolation of a wide variety of somatically derived stem cells has affirmed the notion that homeostatic maintenance of most tissues and organs is mediated by tissue-specific stem and progenitor cells and fueled enthusiasm for the use of such cells in strategies aimed at repairing or replacing damaged, diseased, or genetically deficient tissues and organs. Hematopoietic stem cells (HSCs) are arguably the most well-characterized tissue-specific stem cell, with decades of basic research and clinical application providing not only a profound understanding of the principles of stem cell biology, but also of its potential pitfalls. It is our belief that emerging stem cell fields can benefit greatly from an understanding of the lessons learned from the study of HSCs. In this review we discuss some general concepts regarding stem cell biology learned from the study of HSCs with a highlight on recent work pertaining to emerging topics of interest for stem cell biology.     

The Advancement of Biomaterials in Regulating Stem Cell Fate

Stem cells are well-known to have prominent roles in tissue engineering applications. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can differentiate into every cell type in the body while adult stem cells such as mesenchymal stem cells (MSCs) can be isolated from various sources. Nevertheless, an utmost limitation in harnessing stem cells for tissue engineering is the supply of cells. The advances in biomaterial technology allows the establishment of ex vivo expansion systems to overcome this bottleneck. The progress of various scaffold fabrication could direct stem cell fate decisions including cell proliferation and differentiation into specific lineages in vitro. Stem cell biology and biomaterial technology promote synergistic effect on stem cell-based regenerative therapies. Therefore, understanding the interaction of stem cell and biomaterials would allow the designation of new biomaterials for future clinical therapeutic applications for tissue regeneration. This review focuses mainly on the advances of natural and synthetic biomaterials in regulating stem cell fate decisions. We have also briefly discussed how biological and biophysical properties of biomaterials including wettability, chemical functionality, biodegradability and stiffness play their roles.     

Kidney regeneration by xeno-embryonic nephrogenesis

Establishment of a functional whole kidney de novo has not received much attention because of the formidable challenges and the slow pace of advances in this field of research. This situation has changed recently with publication of data revealing the catastrophic nature of Medicaid costs for dialysis-related diseases. An innovative approach is needed in our search for therapies for kidney diseases and to provide a substitute for dialysis as soon as possible. Regenerative medicine offers great hope for realizing this goal. We established a system by which human mesenchymal stem cells can differentiate into a functional renal unit using a program of nephrogenesis in a developing xeno-embryo. In this article, recent research in the field of developing whole kidneys is reviewed, and possible therapeutic applications for kidney diseases are proposed in combination with our knowledge of the emerging field of kidney stem cell biology.     

Cell therapy for bone regeneration--bench to bedside

The concept of bone tissue engineering, which began in the early 1980s, has seen tremendous growth in the numbers of research studies. One of the key areas of research has been in the field of mesenchymal stem cells, where the challenge is to produce the perfect tissue-engineered bone construct. This practical review summarizes basic and applied state-of-the-art research in the area of mesenchymal stem cells, and highlights the important translational research that has already been initiated. The topics that will be covered include the sources of stem cells in use, scaffolds, gene therapy, clinical applications in nonunions, tumors, osteonecrosis, revision arthroplasties, and spine fusion. Although significant challenges remain, there exists an exceptional opportunity to translate basic research in mesenchymal stem cell technologies into viable clinical treatments for bone regeneration.     

骨、软骨组织工程种子细胞及其免疫学相关研究进展

近年来,细胞生物与生物材料学的迅速发展加快了骨、软骨组织工程的研究.骨、软骨组织工程的系列研究中,种子细胞是骨、软骨组织工程研究的核心内容.本文就骨、软骨组织工程的种子细胞成骨细胞、软骨细胞、骨髓基质细胞、间充质干细胞、胚胎干细胞及其免疫学相关研究进展作一讨论.     

Realizing the cardiac stem cell promise: a case for trophism

Recent advances in stem cell biology have given rise the new field of cardiac regenerative medicine. Specifically, the development of cardiac stem cell science now offers the promise of novel cardiovascular therapies based on a dynamic body of basic and translational research. Importantly, the potential wide-spread clinical application of this technology will require that therapies be optimized for individuals with potential impairments in cardiac stem cell function. To this end, the previous experience of hematopoietic stem cell therapies can provide important guidance in the development and maturation of the young cardiac stem cell field. Parallel to the impact that exogenous growth factors have made in the field of hematopoietic therapies, the discovery and potential application of the factor(s) that govern cardiac regeneration may speed the progression of cardiac stem cell technology into an assessable and potent clinical therapy.     

G-CSF: a key regulator of neutrophil production, but that's not all!

G-CSF is a major extracellular regulator of haemopoiesis and the innate immune system. Named for its relatively specific stimulation of the growth of neutrophil progenitor cells in vitro in semi-solid cultures (Burgess and Metcalf 1980, Nicola et al. 1983), G-CSF influences the survival, proliferation and differentiation of all cells in the neutrophil lineage, from haemopoietic stem cell through to mature neutrophil. Further, G-CSF influences the function of mature neutrophils. These actions underpin its rapid uptake into clinical medicine as a drug that increases the production of neutrophils in patients with chemotherapy-induced neutropenia.Ongoing research has uncovered initially unsuspected polyfunctionality for G-CSF. G-CSF is well recognised as a potent mobiliser of haemopoietic stem cells from the bone marrow into the blood, and now is being increasingly accepted as a regulator of immune responses. These two "new" actions of G-CSF first came to light through observations made during clinical trials of G-CSF. Subsequent investigations into the cellular and molecular basis for this polyfunctionality have generated exciting new knowledge about the biology of G-CSF. This review emphasises recent advances in knowledge about G-CSF signalling, mechanisms of G-CSF-induced stem cell mobilisation, and how G-CSF influences T-cell function and dendritic cell activation. An attempt is made to link the current issues about the biology of G-CSF with its clinical uses, both present and future.     

胚胎干细胞定向分化的研究进展

胚胎干细胞已成为组织工程、发育生物学、药物开发及基因研究的热点。本文仅就胚胎干细胞定向分化的机制、研究进展和应用前景作一综述 ,旨在进一步推动胚胎干细胞的研究工作。     

Progress and Promise Towards Safe Induced Pluripotent Stem Cells for Therapy

The recent generation of induced pluripotent stem cells (iPSCs) from somatic cells provides an invaluable resource for drug or toxicology screening, medical research, and patient-specific cell therapy. However, there are currently a number of obstacles including virus integration and the genetic alteration of iPSCs that will need to be overcome before these cells may be considered safe for clinical applications. Here, we highlight the potential and challenges of iPSC research and review advances in reprogramming methods that have rapidly moved the field closer to realizing the goal of generating safe iPSCs for transplantation.     

Redox regulation of stem and progenitor cells

The field of stem and progenitor cell biology is expanding. Much of the enthusiasm is based on the potential of using stem and progenitor cells as a cellular therapy for the treatment of human disease. Although the concept of using human embryonic stem cells for therapeutic indications is intriguing, significant challenges face investigators pursuing research in this area. Therefore, renewed scientific energy is focusing on the molecular pathways that differentiate a pluripotent embryonic stem cell from more-committed tissue-specific cells. Molecular mechanisms that govern tissue-specific stem and progenitor cell function are also topics of intense investigation, given that altered function of these cells may promote a variety of human pathologies including aging, vascular disease, and cancer. Considerable progress has been made, but a clear identification of the molecular signatures of stem and progenitor cells remains elusive. A growing body of literature demonstrates that distinct functional characteristics of stem and progenitor cells are under redox regulation. In this Forum Issue, evidence for redox regulation of tissue-specific stem and progenitor cells involved in hematopoiesis and vasculogenesis/angiogenesis is presented.     

G-CSF: A key regulator of neutrophil production,but that's not all!

G-CSF is a major extracellular regulator of haemopoiesis and the innate immune system. Named for its relatively specific stimulation of the growth of neutrophil progenitor cells in vitro in semi-solid cultures (Burgess and Metcalf 1980, Nicola et al. 1983), G-CSF influences the survival, proliferation and differentiation of all cells in the neutrophil lineage, from haemopoietic stem cell through to mature neutrophil. Further, G-CSF influences the function of mature neutrophils. These actions underpin its rapid uptake into clinical medicine as a drug that increases the production of neutrophils in patients with chemotherapy-induced neutropenia.

Ongoing research has uncovered initially unsuspected polyfunctionality for G-CSF. G-CSF is well recognised as a potent mobiliser of haemopoietic stem cells from the bone marrow into the blood, and now is being increasingly accepted as a regulator of immune responses. These two “new” actions of G-CSF first came to light through observations made during clinical trials of G-CSF. Subsequent investigations into the cellular and molecular basis for this polyfunctionality have generated exciting new knowledge about the biology of G-CSF. This review emphasises recent advances in knowledge about G-CSF signalling, mechanisms of G-CSF-induced stem cell mobilisation, and how G-CSF influences T-cell function and dendritic cell activation. An attempt is made to link the current issues about the biology of G-CSF with its clinical uses, both present and future.     

No relationship between the distribution of mast cells and the survival of stage IIIB colon cancer patients

The field of cellular therapy of cancer is moving quickly and the issues involved with its advancement are complex and wide ranging. The growing clinical applications and success of adoptive cellular therapy of cancer has been due to the rapid evolution of immunology, cancer biology, gene therapy and stem cell biology and the translation of advances in these fields from the research laboratory to the clinic. The continued development of this field is dependent on the exchange of ideas across these diverse disciplines, the testing of new ideas in the research laboratory and in animal models, the development of new cellular therapies and GMP methods to produce these therapies, and the testing of new adoptive cell therapies in clinical trials. The Summit on Cell Therapy for Cancer to held on November 1 and 2, 2011 at the National Institutes of Health (NIH) campus will include a mix of perspectives, concepts and ideas related to adoptive cellular therapy that are not normally presented together at any single meeting. This novel assembly will generate new ideas and new collaborations and possibly increase the rate of advancement of this field.     

Advances in Mesenchymal Stem Cell-based Strategies for Cartilage Repair and Regeneration

Significant research efforts have been undertaken in the last decade in the development of stem cell-based therapies for cartilage repair. Among the various stem cell sources, mesenchymal stem cells (MSCs) demonstrate great promise and clinical efficacy in cartilage regeneration. With a deeper understanding of stem cell biology, new therapeutics and new bioengineering approaches have emerged and showed potential for further developments. Of note, there has been a paradigm shift in applying MSCs for tissue regeneration from the use of stem cells for transplantation to the use of stem cell-derived matrix and secretome components as therapeutic tools and agents for cartilage regeneration. In this review, we will discuss the emerging role of MSCs in cartilage regeneration and the most recent advances in development of stem cell-based therapeutics for cartilage regeneration.     

Can hematopoietic stem cells be an alternative source for skin regeneration?

In the past few years, the plasticity of adult cells in several post-natal tissues has attracted special attention in regenerative medicine. Skin is the largest organ in the body. Adult skin consists of epidermis, dermis and appendages such as hair and glands that are linked to the epidermis but project deep into the dermal layer. Stem cell biology of skin has been a focus of increasing interest in current life science. Committed stem cells with a limited differentiation potential for regeneration and repair of epidermis have been known for decades. Recent studies further found that adult skin tissues contain cell populations with pluripotent characteristics. Multipotent stem cells from skin with and without hair follicles, both in epidermal and dermal tissues, can differentiate and generate multiple cell lineages. Especially, the hematopoietic system in epidermal and dermal tissue, like skin, may be a local, acceptable reservoir of various adult stem cell populations. Given their easy accessibility, such stem cells can provide an experimental model not only for skin biology but also for studying the epithelial–mesenchymal cell interactions of organs other than the skin. This review presents an overview of recent advances in research into skin repair and regeneration involving stem cells from epidermis, dermis, and bone marrow. In particular, we focus on the possible use of blood stem cells as an alternative resource for research advances in skin biology.     

Mesenchymal Stem/Progenitor Cells Derived from Articular Cartilage,Synovial Membrane and Synovial Fluid for Cartilage Regeneration: Current Status and Future Perspectives

Large articular cartilage defects remain an immense challenge in the field of regenerative medicine because of their poor intrinsic repair capacity. Currently, the available medical interventions can relieve clinical symptoms to some extent, but fail to repair the cartilaginous injuries with authentic hyaline cartilage. There has been a surge of interest in developing cell-based therapies, focused particularly on the use of mesenchymal stem/progenitor cells with or without scaffolds. Mesenchymal stem/progenitor cells are promising graft cells for tissue regeneration, but the most suitable source of cells for cartilage repair remains controversial. The tissue origin of mesenchymal stem/progenitor cells notably influences the biological properties and therapeutic potential. It is well known that mesenchymal stem/progenitor cells derived from synovial joint tissues exhibit superior chondrogenic ability compared with those derived from non-joint tissues; thus, these cell populations are considered ideal sources for cartilage regeneration. In addition to the progress in research and promising preclinical results, many important research questions must be answered before widespread success in cartilage regeneration is achieved. This review outlines the biology of stem/progenitor cells derived from the articular cartilage, the synovial membrane, and the synovial fluid, including their tissue distribution, function and biological characteristics. Furthermore, preclinical and clinical trials focusing on their applications for cartilage regeneration are summarized, and future research perspectives are discussed.     

Muscle stem cells in development, regeneration, and disease

Somatic stem cell populations participate in the development and regeneration of their host tissues. Skeletal muscle is capable of complete regeneration due to stem cells that reside in skeletal muscle and nonmuscle stem cell populations. However, in severe myopathic diseases such as Duchenne Muscular Dystrophy, this regenerative capacity is exhausted. In the present review, studies will be examined that focus on the origin, gene expression, and coordinated regulation of stem cell populations to highlight the regenerative capacity of skeletal muscle and emphasize the challenges for this field. Intense interest has focused on cell-based therapies for chronic, debilitating myopathic diseases. Future studies that enhance our understanding of stem cell biology and repair mechanisms will provide a platform for therapeutic applications directed toward these chronic, life-threatening diseases.     

The International Society for Stem Cell Research (ISSCR): history and perspectives

The International Society for Stem Cell Research (ISSCR) is an independent, nonprofit organization founded in 2002 to foster professional and public communication and education regarding stem cell research. Under the leadership of prominent stem cell scientists from around the world, the ISSCR membership has grown exponentially, creating a diverse, international community of researchers who have expertise in many facets of stem cell biology. The ISSCR is dedicated to promoting the exchange of ideas and has developed two major forums for dissemination of stem cell research and related issues, an annual meeting and an information-rich website. With the field of stem cell research and technologies rapidly advancing, discourse is more critical than ever to maintain high standards across the full spectrum of research.     

Concise review: putting a finger on stem cell biology: zinc finger nuclease-driven targeted genetic editing in human pluripotent stem cells

Human pluripotent stem cells (hPSCs) encompassing human embryonic stem cells and human induced pluripotent stem cells (hiPSCs) have a wide appeal for numerous basic biology studies and for therapeutic applications because of their potential to give rise to almost any cell type in the human body and immense ability to self-renew. Much attention in the stem cell field is focused toward the study of gene-based anomalies relating to the causative affects of human disease and their correction with the potential for patient-specific therapies using gene corrected hiPSCs. Therefore, the genetic manipulation of stem cells is clearly important for the development of future medicine. Although successful targeted genetic engineering in hPSCs has been reported, these cases are surprisingly few because of inherent technical limitations with the methods used. The development of more robust and efficient means by which to achieve specific genomic modifications in hPSCs has far reaching implications for stem cell research and its applications. Recent proof-of-principle reports have shown that genetic alterations with minimal toxicity are now possible through the use of zinc finger nucleases (ZFNs) and the inherent DNA repair mechanisms within the cell. In light of recent comprehensive reviews that highlight the applications, methodologies, and prospects of ZFNs, this article focuses on the application of ZFNs to stem cell biology, discussing the published work to date, potential problems, and future uses for this technology both experimentally and therapeutically.