Journal of Stem Cells最新文献

Tissue is frequently damaged or lost in injury and disease. There has been an increasing interest in stem cell applications and tissue engineering approaches in surgical practice to deal with damaged or lost tissue. Tissue engineering is an exciting strategy being explored to deal with damaged or lost tissue. It is the science of generating tissue using molecular and cellular techniques, combined with material engineering principles, to replace tissue. This could be in the form of cells with or without matrices. Although there have been developments in almost all surgical disciplines, the greatest advances are being made in orthopaedics, especially in cartilage repair. This is due to many factors including the familiarity with bone marrow derived mesenchymal stem cells and cartilage being a relatively simpler tissue to engineer. Unfortunately significant hurdles remain to be overcome in many areas before tissue engineering becomes more routinely used in clinical practice. Cells used in tissue engineering could be autologous, allogeneic or xenogeneic. The cells could be stem cells or cells further down the differentiation pathway. The use of embryonic stem cells is associated with religious, political and social concerns, but the use of adult stem cells is generally well accepted. Stem cells have been identified in a number of adult tissues, albeit in small numbers. In addition to bone marrow, mesenchymal stem cells have been identified in a number of tissues including adipose tissue and fat pad. The mesenchymal stem cells are generally isolated from the tissue and expanded in culture. These cells can be differentiated down a particular differentiation pathway e.g. osteoblast or chondrocyte, using predefined culture conditions before being used for clinical applications. In this paper stem cells are discussed including their various sources and their differentiation potential.

Tissue is frequently damaged or lost in injury and disease. There has been an increasing interest in stem cell applications and tissue engineering approaches in surgical practice to deal with damaged or lost tissue. Although there have been developments in almost all surgical disciplines, the greatest advances are being made in orthopaedics, especially in cartilage repair. This is due to many factors including the familiarity with bone marrow derived mesenchymal stem cells and cartilage being a relatively simpler tissue to engineer. Unfortunately significant hurdles remain to be overcome in many areas before tissue engineering becomes more routinely used in clinical practice. In this paper we discuss the structure, function and embryology of cartilage and osteoarthritis. This is followed by a review of current treatment strategies for the repair of cartilage and the use of tissue engineering.

Recent advances in induced pluripotent stem (iPS) cell research have attracted much attention. The ability to generate such cells from somatic cells has implications for overcoming both immunological rejection and the ethical issues associated with embryonic stem (ES) cells. Hepatocytes derived from patient-specific iPS cells offer a possible solution to the shortage of cell sources in cell replacement therapy, drug screening, and disease model. Despite such great promise, however, recent articles have questioned the viability of the therapeutic applications of iPS cells. These cells must, therefore, satisfy stringent criteria prior to practical use. The main focus of this review is a description of the current status of hepatic differentiation technology of iPS cells and a discussion of the concerns regarding the practical use of these techniques in cell replacement therapy, drug screening, and disease model. The current status of strategies for generating iPS cells and the accumulated knowledge on strategies for differentiating ES cells into hepatocytes will be summarized. We also refer to the possibility of direct conversion of adult somatic cells into functional hepatocytes.

Stem cells, derived from either embryonic or adult tissues, are considered to be potential sources of insulin-secreting cells to be transplanted into type 1 and advanced stages of type 2 diabetic patients. Many laboratories have considered this possibility, resulting in a large amount of published protocols, with a wide degree of complexity among them. Our group was the first to report that it was possible to obtain insulin-secreting cells from mouse embryonic stem cells, proving the feasibility of this new challenge. The same observation was immediately reported using human embryonic stem cells. However, the resulting cell product was not properly characterised, affecting the reproducibility of the protocol by other groups. A more elaborated protocol was developed by Lumelsky and co-workers, demonstrating that neuroectodermal cells could be an alternative source for insulin-producing cells. However, the resulting cells of this protocol produced low amounts of the hormone. This aimed other groups to perform key changes in order to improve the insulin content of the resulting cells. Recently, Baetge's group has published a new protocol based on the knowledge accumulated in pancreatic development. In this protocol, human embryonic stem cells were differentiated into islet-like structures through a five step protocol, emulating the key steps during embryonic development of the endocrine pancreas. The final cell product, however, seemed to be in an immature state, thus further improvement is required. Despite this drawback, the protocol represents the culmination of work performed by different groups and offers new research challenges for the investigators in this exciting field. Concerning adult stem cells, the possibility of identifying pancreatic precursors or of reprogramming extrapancreatic derived cells are key possibilities that may circumvent the problems that appear when using embryonic stem cells, such as immune rejection and tumour formation.

Diabetes mellitus is a devastating disease and the World Health Organization (WHO) expects that the number of diabetic patients will increase to 300 million by the year 2025. Patients with diabetes experience decreased insulin secretion that is linked to a significant reduction in the number of islet cells. Type 1 diabetes is characterized by the selective destruction of pancreatic β cells caused by an autoimmune attack. Type 2 diabetes is a more complex pathology that, in addition to β cell loss caused by apoptotic programs, includes β cell de-differentiation and peripheric insulin resistance. The success achieved over the last few years with islet transplantation suggests that diabetes can be cured by the replenishment of deficient β cells. These observations are proof of the concept and have intensified interest in treating diabetes or other diseases not only by cell transplantation but also by stem cells. An increasing body of evidence indicates that, in addition to embryonic stem cells, several potential adult stem/progenitor cells derived from the pancreas, liver, spleen, and bone marrow could differentiate into insulin-producing cells in vitro or in vivo. However, significant controversy currently exists in this field. Pharmacological approaches aimed at stimulating the in vivo/ex vivo regeneration of β cells have been proposed as a way of augmenting islet cell mass. Overexpression of embryonic transcription factors in stem cells could efficiently induce their differentiation into insulin-expressing cells. A new technology, known as protein transduction, facilitates the differentiation of stem cells into insulin-producing cells. Recent progress in the search for new sources of β cells has opened up several possibilities for the development of new treatments for diabetes.

Cancer stem cells (CSCs) are stem-like tumor populations that are reported to contribute towards tumor growth, maintenance and recurrence after therapy. Hypoxia increases CSC fraction and promotes acquisition of a stem-cell-like state. Cancer stem cells are critically dependant on the hypoxia-inducible factor-1 (HIF-1) for survival, self-renewal, tumor growth and maintenance of their undifferentiated phenotype. Recent researches show that stage of differentiation of the tumor cells is predictive of their susceptibility to natural killer cell (NK) cell mediated cytotoxicity and cancer stem cells are significant targets of NK cell cytotoxicity. Studies also show that reversion of tumor cells to a less-differentiated phenotype can be achieved by blocking NFκB. Yoga therapy (yogic lifestyle modifications encompassing physical postures, breathing practices, relaxation techniques and meditations) is known to modulate neural, endocrine and immune functions at the cellular level through influencing cell cycle control, aging, oxidative stress, apoptosis and several pathways of stress signaling molecules. Yoga therapy has also been shown to enhance natural killer cell activity and modulate stress and DNA damage in breast cancer patients receiving radiotherapy. Recent study found that brief daily yogic meditation may reverse the pattern of increased NFκB-related transcription of pro-inflammatory cytokines in leukocytes. Thus, yoga therapy has the potential to reduce cancer stem cell survival, self -renewal and tumor growth by modifying the tumor micro-environment through various mechanisms such as; 1) reducing HIF-1 activity by enhanced oxygenation, 2) promoting NK cell activity directly (or indirectly through down regulating NFκB expression), thereby enhancing NK cell mediated CSC lysis, and 3) by minimizing the aberrant expressions or activities of various hormones, cytokines, chemokines and tumor signaling pathways. Yoga therapy may have a synergistic effect with conventional modalities of treatment in preventing cancer progression and recurrences.

Context and aim: Complementary and alternative therapies (CAM) are gaining popularity amongst patients as add on to conventional medicine. Yoga stands third amongst all CAM that is being used by cancer patients today. Different schools of yoga use different sets of practices, with some using a more physical approach and many using meditation and/or breathing. All these modules are developed based on the needs of the patient. This paper is an attempt to provide the basis for a comprehensive need based integrative yoga module for cancer patients at different stages of treatment and follow up. In this paper, the holistic modules of the integrated approach of yoga therapy for cancer (IAYTC) have been developed based on the patient needs, as per the observations by the clinicians and the caregivers. Authors have attempted to systematically create holistic modules of IAYTC for various stages of the disease and treatment. These modules have been used in randomized trials to evaluate its efficacy and have shown to be effective as add-on to conventional management of cancer. Thus, the objective of this effort was to present the theoretical basis and validate the need based holistic yoga modules for cancer patients.

Materials and methods: Literature from traditional texts including Vedas, Ayurveda, Upanishads, Bhagavat Gita, Yoga Vasishtha etc. and their commentaries were looked into for references of cancer and therapeutic directives. Present day scientific literature was also explored with regards to defining cancer, its etiopathology and its management. Results of studies done using CAM therapies were also looked at, for salient findings. Focused group discussions (FGD) amongst researchers, experienced gurus, and medical professionals involved in research and clinical cancer practice were carried out with the objectives of determining needs of the patient and yoga practices that could prove efficient. A list of needs at different stages of conventional therapies (surgery, chemotherapy and radiation therapy) was listed and yoga modules were developed accordingly. Considering the needs, expected side effects, the energy levels and the psychological states of the participants, eight modules evolved.

Results: The results of the six steps for developing the validated module are reported. Step 1: Literature review from traditional yoga and ayurveda texts on etiopathogenesis and management of cancer (arbuda), and the recent literature on cancer stem cells and immunology of cancer. Step 2: Focused group discussions and deliberations to compile the needs of patients based on the expected side effects, energy levels and the psychological state of the patient as observed by the caregivers and the clinicians. Step 3: Content validation through consensus by the experts for the eight modules of IAYTC that could be used as complimentary to conventional management of cancer at different stages during and

Tendon injuries are common and due to their limited capacity for self-healing, the biomechanical and functional properties of healed tendon are usually inferior to normal tissue. Tissue engineering offers the hope of regenerating tendon tissue with the same biomechanical properties of the native undamaged tissue by augmenting the regenerative process of in vivo tissue or producing a functional tissue in vitro that can be implanted into the defective tendon site. Current research on tendon tissue engineering has focused on the role of stem cell and tendon derived cell therapy, scaffolds, chemical and physical stimulation and gene-therapeutic approaches. In this review we review the important functional anatomy and pathomechanics of tendon injury and discuss the current advances in tendon tissue engineering.

Formation of specialized spatial structures comprising various cell types is most important in the ontogenesis of multicellular organisms. An example is the D. melanogaster bristle organs. Bristles (micro- and macrochaetes) are external sensory organs, elements of the peripheral nervous system, playing the role of mechanoreceptors. Their comparatively simple organization comprising only four specialized cells and a common origin of these cells make macrochaetes a convenient model for studying cell differentiation. The four cells forming bristle organ result from two successive divisions of a single cell, sensory organ precursor (SOP) cell. The number of macrochaetes on drosophila body corresponds to the number of SOP cells. The morphogenesis of macrochaetes comprises three stages, the first two determining a neural fate of the cells. The third stage is cell specialization into components of the bristle organ-neuron, thecogen, tormogen, and trichogen. Development of each bristle commences from segregation of proneural clusters, of 20-30 cells, from the massif of undifferentiated cells of the wing imaginal disc. At this stage, each cluster cell can potentially become a SOP cell. At the second stage, the only SOP cell and its position are determined within each cluster. Finally, two asymmetric divisions of the SOP cell with subsequent differentiation of the daughter cells gives the bristle organ. Several dozens genes are involved in the control of macrochaete morphogenesis. The main component of this system is the proneural genes of achaete-scute complex (AS-C). An increased content of proneural proteins fundamentally distinguished the cells that will follow the neural developmental pathway from the disc epidermal cells. A local AS-C expression, initiated at specified disc sites by specific transcription factors, determines the number and topology of proneural clusters. The expression of AS-C genes, continuing in the cells of the cluster, increases the difference in proneural protein content, first, between the cluster cells and then, between the cluster cells and the single SOP cell, where it reaches the maximum level. This process is provided by both the intracellular regulation of AS-C gene activity and intercellular events mediated via the EGFR and Notch signaling pathways. The third stage in macrochaete morphogenesis comprises two successive asymmetric SOP cell divisions, determining the final specialization. The selector genes, in particular, numb, neuralized, tramtrack, and musashi, play the key role in cell type specification. This review systematizes the data on molecular genetic system controlling drosophila bristle morphogenesis and proposes an integral scheme of its functioning.

There has been an increasing interest in stem cell applications and tissue engineering approaches in surgical practice to deal with damaged or lost tissue. Although there have been developments in almost all surgical disciplines, the greatest advances are being made in orthopaedics. This is due to many factors including the familiarity with bone marrow derived mesenchymal stem cells. Unfortunately significant hurdles remain to be overcome in many areas before tissue engineering becomes more routinely used in clinical practice. Stem cells have been identified in a number of adult tissues, albeit in small numbers. In addition to bone marrow, mesenchymal stem cells have been identified in a number of tissues including adipose tissue and fat pad. The mesenchymal stem cells are generally isolated from the tissue and expanded in culture. These cells are characterised or defined using a set of cell surface markers; mesenchymal stem cells are generally positive for CD44, CD90 and CD105, and are negative for haematopoetic markers CD34 and CD45, and the neurogenic marker CD56. In this paper the characterisation of stem cells is discussed followed by preliminary evidence suggesting that pericytes may be a candidate stem cell.