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Cell Therapy (cell + therapy)
Kinds of Cell Therapy Selected AbstractsGene and Cell Therapy for Heart DiseaseIUBMB LIFE, Issue 2 2002Regina M. Graham Abstract Heart disease is the most common cause of morbidity and mortality in Western society and the incidence is projected to increase significantly over the next few decades as our population ages. Heart failure occurs when the heart is unable to pump blood at a rate to commensurate with tissue metabolic requirements and represents the end stage of a variety of pathological conditions. Causes of heart failure include ischemia, hypertension, coronary artery disease, and idiopathic dilated cardiomyopathy. Hypertension and ischemia both cause infarction with loss of function and a consequent contractile deficit that promotes ventricular remodeling. Remodeling results in dramatic alterations in the size, shape, and composition of the walls and chambers of the heart and can have both positive and negative effects on function. In 30-40% of patients with heart failure, left ventricular systolic function is relatively unaffected while diastolic dysfunction predominates. Recent progress in our understanding of the molecular and cellular bases of heart disease has provided new therapeutic targets and led to novel approaches including the delivery of proteins, genes, and cells to replace defective or deficient components and restore function to the diseased heart. This review focuses on three such strategies that are currently under development: (a) gene transfer to modulate contractility, (b) therapeutic angiogenesis for the treatment of ischemia, and (c) embryonic and adult stem cell transfer to replace damaged myocardium. [source] From Genes to Cell Therapy: Molecular Medicine Meets Clinical EPJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 5 2005Ph.D., SILVIA G. PRIORI M.D. No abstract is available for this article. [source] Muscle-derived Stem Cell Therapy for Stress Urinary IncontinenceLUTS, Issue 2009Shing-Hwa LU The aim of the present article is to overview the potential of muscle-derived stem cells and other cellular therapy for urethral regeneration and to review the clinical experiences of its application in patients with stress urinary incontinence. [source] Cell Therapy for Cardiovascular Disorders: Coming of Age?ARTIFICIAL ORGANS, Issue 4 2006Paul S. Malchesky D. Eng. No abstract is available for this article. [source] Stem Cell Therapy as the Reinforcement of Organ RegenerationARTIFICIAL ORGANS, Issue 5 2005Dorota Fiszer Dr. No abstract is available for this article. [source] Immunostimulatory Effects of Mesenchymal Stem Cell-Derived Neurons: Implications for Stem Cell Therapy in Allogeneic TransplantationsCLINICAL AND TRANSLATIONAL SCIENCE, Issue 1 2008Marianne D. Castillo Abstract Mesenchymal stem cells (MSCs) differentiate along various lineages to specialized mesodermal cells and also transdifferentiate into cells such as ectodermal neurons. MSCs are among the leading adult stem cells for application in regenerative medicine. Advantages include their immune-suppressive properties and reduced ethical concerns. MSCs also show immune-enhancing functions. Major histocompatibility complex II (MHC-II) is expected to be downregulated in MSCs during neurogenesis. Ideally, "off the shelf" MSCs would be suited for rapid delivery into patients. The question is whether these MSC-derived neurons can reexpress MHC-II in a milieu of inflammation. Western analyses demonstrated gradual decrease in MHC-II during neurogenesis, which correlated with the expression of nuclear CIITA, the master regulator of MHC-II expression. MHC-II expression was reversed by exogenous IFNY. One-way mixed lymphocyte reaction with partly differentiated neurons showed a stimulatory effect, which was partly explained by the release of the proinflammatory neurotransmitter substance P (SP), cytokines, and decreases in miR-130a and miR-206. The anti-inflammatory neurotransmitters VIP and CGRP were decreased at the peak time of immune stimulation. In summary, MSC-derived neurons show decreased MHC-II expression, which could be reexpressed by IFNY. The release of neurotransmitters could be involved in initiating inflammation, underscoring the relevance of immune responses as consideration for stem cell therapies. [source] Cell therapies: realizing the potential of this new dimension to medical therapeuticsJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 6 2008Pawanbir Singh Abstract Stem cells promise to treat conditions poorly served by conventional therapeutics. Cells from both embryonic and somatic tissues are being used to create cell therapies for genetic, traumatic and degenerative conditions. The current human, healthcare and fiscal costs of these conditions are significant. This review summarizes the use of stem cells for neurological and cardiac disorders and diabetes to determine the requirements for generic translational research to assist such therapies to be a reality. While there are multiple strategies in each disease area, with no clear favourite, there are clear opportunities in treatments that use a single cell type. A key requirement is to work with pluripotent progenitor cells to cultivate and differentiate a sufficiently large population of functioning cells. Challenges also arise in determining and achieving timely delivery of the correct dose of cells to where they can most effectively treat the disease and best benefit individual patients. Copyright © 2008 John Wiley & Sons, Ltd. [source] Complementary and alternative therapies for Down syndromeDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2005Nancy J. Roizen Abstract In their role as committed advocates, parents of children with Down syndrome have always sought alternative therapies, mainly to enhance cognitive function but also to improve their appearance. Nutritional supplements have been the most frequent type of complementary and alternative therapy used. Cell therapy, plastic surgery, hormonal therapy, and a host of other therapies such as massage therapy have been used. There is a lack of well-designed scientific studies on the use of alternative therapies in individuals with Down syndrome. Antioxidants hold theoretical promise for treatment of the cognitive, immune, malignancy, and premature aging problems associated with Down syndrome. Medications for treatment of Alzheimer's disease may also result in benefit for the population of individuals with Down syndrome. © 2005 Wiley-Liss, Inc. MRDD Research Reviews 2005;11:149,155. [source] Cardiovascular cell therapy and endogenous repairDIABETES OBESITY & METABOLISM, Issue 2008D. A. Taylor Cardiovascular disease (CVD) exceeds infection and cancer as the leading cause of death. In the USA alone, approximately a million individuals suffer an acute myocardial infarction (AMI) annually. As the prevalence of CVD risk factors (e.g. hypertension, obesity and type 2 diabetes) rises, CVD is increasing in younger individuals. Fortunately, existing therapies have improved post-AMI mortality, but in turn have increased the prevalence of post-AMI heart failure (HF). Approximately half-a-million new HF cases are diagnosed each year in the USA. In the next 25 years, up to 15% of the population over the age of 65 in the USA is projected to have HF. Therapeutic interventions that prevent/reverse atherosclerosis, prevent post-AMI HF and halt the progressive functional deterioration once HF occurs are all needed. Cell therapy , either via exogenous delivery or by endogenous mobilization of cells , may be able to do so, in part, by improving the body's capacity for repair. To date, primarily bone marrow- or blood-derived cells have been utilized after AMI to prevent left ventricular dysfunction, and skeletal myoblasts have been transplanted into failing myocardium. Preclinical studies are directed at prevention/reversal of atherosclerosis with bone marrow precursors, and ultimately at replacing failing heart with a cell-based bioartificial construct. [source] A new paradigm in cell therapy for diabetes: Turning pancreatic ,-cells into ,-cellsBIOESSAYS, Issue 10 2010Caroline B. Sangan Cell therapy means treating diseases with the body's own cells. One of the cell types most in demand for therapeutic purposes is the pancreatic ,-cell. This is because diabetes is one of the major healthcare problems in the world. Diabetes can be treated by islet transplantation but the major limitation is the shortage of organ donors. To overcome the shortfall in donors, alternative sources of pancreatic ,-cells must be found. Potential sources include embryonic or adult stem cells or, from existing ,-cells. There is now a startling new addition to this list of therapies: the pancreatic ,-cell. Thorel and colleagues recently showed that under circumstances of extreme pancreatic ,-cell loss, ,-cells may serve to replenish the insulin-producing compartment. This conversion of ,-cells to ,-cells represents an example of transdifferentiation. Understanding the molecular basis for transdifferentiation may help to enhance the generation of ,-cells for the treatment of diabetes. [source] Bifunctional Eu3+ -doped Gd2O3 nanoparticles as a luminescent and T1 contrast agent for stem cell labelingCONTRAST MEDIA & MOLECULAR IMAGING, Issue 2 2010Zhilong Shi Abstract Magnetic resonance tracking of stem cells has recently become an emerging application for investigating cell,tissue interactions and guiding the development of effective stem cell therapies for regeneration of damaged tissues and organs. In this work, anionic Eu3+ -doped Gd2O3 hybrid nanoparticles were applied as a contrast agent both for fluorescence microscopy and T1 -weighted MRI. The nanoparticles were synthesized through the polyol method and further modified with citric acid to obtain anionic nanoparticles. These nanoparticles were internalized into human mesenchymal stem cells (hMSCs) as confirmed by confocal laser scanning microscopy and quantified by inductively coupled plasma,mass spectrometry. MTT assay of the labeled cells showed that the nanoparticles did not possess significant cytotoxicity. In addition, the osteogenic, adipogenic and chondrogenic differentiation of the hMSCs was not influenced by the labeling process. With MRI, the in vitro detection threshold of cells after incubation with nanoparticles at a Gd concentration of 0.5,mMfor 2,h was estimated to be about 10 000 cells. The results from this study indicate that the biocompatible anionic Gd2O3 nanoparticles doped with Eu3+ show promise both as a luminescent and T1 contrast agent for use in visualizing hMSCs. Copyright © 2010 John Wiley & Sons, Ltd. [source] Stemness, fusion and renewal of hematopoietic and embryonic stem cellsJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 2 2003S. Constantinescu Abstract Development of replacement cell therapies awaits the identification of factors that regulate nuclear reprogramming and the mechanisms that control stem cell renewal and differentiation. Once such factors and signals will begin to be elucidated, new technologies will have to be envisaged where uniform differentiation of adult or embryonic stem cells along one differentiation pathway can be induced. Controlled differentiation of stem cells will require the engineering of niches and extracellular signal combinations that would amplify a particular signaling network and allow uniform and selective differentiation. Three recent advances in stem cell research open the possibility to approach engineering studies for cell replacement therapies. Fusion events between stem cells and adult cells or between adult and embryonic stem cells have been shown to result in altered fates and nuclear reprogramming of cell hybrids. Hematopoietic stem cells were shown to require Wnt signaling in order to renew. The purification of Wnt proteins would allow their use as exogenous purified cytokines in attempts to amplify stem cells before bone marrow transplantation. The homeodomain protein Nanog has been shown to be crucial for the embryonic stem cell renewal and pluripotency. However, the cardinal question of how stemness is preserved in the early embryo and adult stem cells remains opened. [source] Endomyocardial biopsy derived adherent proliferating cells,A potential cell source for cardiac tissue engineeringJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2010Marion Haag Abstract Heart diseases are a leading cause of morbidity and mortality. Cardiac stem cells (CSC) are considered as candidates for cardiac-directed cell therapies. However, clinical translation is hampered since their isolation and expansion is complex. We describe a population of human cardiac derived adherent proliferating (CAP) cells that can be reliably and efficiently isolated and expanded from endomyocardial biopsies (0.1,cm3). Growth kinetics revealed a mean cell doubling time of 49.9,h and a high number of 2.54,×,107 cells in passage 3. Microarray analysis directed at investigating the gene expression profile of human CAP cells demonstrated the absence of the hematopoietic cell markers CD34 and CD45, and of CD90, which is expressed on mesenchymal stem cells (MSC) and fibroblasts. These data were confirmed by flow cytometry analysis. CAP cells could not be differentiated into adipocytes, osteoblasts, chondrocytes, or myoblasts, demonstrating the absence of multilineage potential. Moreover, despite the expression of heart muscle markers like ,-sarcomeric actin and cardiac myosin, CAP cells cannot be differentiated into cardiomyocytes. Regarding functionality, CAP cells were especially positive for many genes involved in angiogenesis like angiopoietin-1, VEGF, KDR, and neuropilins. Globally, principal component and hierarchical clustering analysis and comparison with microarray data from many undifferentiated and differentiated reference cell types, revealed a unique identity of CAP cells. In conclusion, we have identified a unique cardiac tissue derived cell type that can be isolated and expanded from endomyocardial biopsies and which presents a potential cell source for cardiac repair. Results indicate that these cells rather support angiogenesis than cardiomyocyte differentiation. J. Cell. Biochem. 109: 564,575, 2010. © 2009 Wiley-Liss, Inc. [source] Review article: stem cell therapies for inflammatory bowel disease , efficacy and safetyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2010O. García-Bosch Aliment Pharmacol Ther 2010; 32: 939,952 Summary Background, Drugs available for the treatment of inflammatory bowel disease fail to induce and maintain remission in a significant number of patients. Aim, To assess the value of stem cell therapies for treatment of inflammatory bowel disease based on published studies. Methods, Publications were identified through a MEDLINE search using the Medical Subject Heading terms: inflammatory bowel diseases, or Crohn's disease, or ulcerative colitis, and stem cell, or stromal cell or transplant. Results, Haematopoietic stem cell therapy as a primary treatment for inflammatory bowel disease was originally supported by animal experiments, and by remissions in patients undergoing transplant for haematological disorders. Later, transplantation specifically performed for patients with refractory Crohn's disease showed long-lasting clinical remission and healing of inflammatory intestinal lesions. Use of autologous nonmyeloablative regimens and concentration of the procedures in centres with large experience are key in reducing treatment-related mortality. Initial trials of mesenchymal stem cell therapy with local injection in Crohn's perianal fistulas had positive results. Conclusions, Autologous haematopoietic stem cell transplant changes the natural course of Crohn's disease, and may be a therapeutic option in patients with refractory disease if surgery is not feasible due to disease location or extension. [source] Cell therapies: realizing the potential of this new dimension to medical therapeuticsJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 6 2008Pawanbir Singh Abstract Stem cells promise to treat conditions poorly served by conventional therapeutics. Cells from both embryonic and somatic tissues are being used to create cell therapies for genetic, traumatic and degenerative conditions. The current human, healthcare and fiscal costs of these conditions are significant. This review summarizes the use of stem cells for neurological and cardiac disorders and diabetes to determine the requirements for generic translational research to assist such therapies to be a reality. While there are multiple strategies in each disease area, with no clear favourite, there are clear opportunities in treatments that use a single cell type. A key requirement is to work with pluripotent progenitor cells to cultivate and differentiate a sufficiently large population of functioning cells. Challenges also arise in determining and achieving timely delivery of the correct dose of cells to where they can most effectively treat the disease and best benefit individual patients. Copyright © 2008 John Wiley & Sons, Ltd. [source] Magnetosonoporation: Instant magnetic labeling of stem cellsMAGNETIC RESONANCE IN MEDICINE, Issue 6 2010Bensheng Qiu Abstract The purpose of this study was to develop an instant MR cell labeling technique, called magnetosonoporation. First, a magnetosonoporation apparatus was successfully established for MR labeling of stem cells. Then, the safety of this new cell labeling approach was confirmed by evaluation of cell viability, proliferation, and differentiation of magnetosonoporation-labeled and unlabeled C17.2 neural stem cells. Subsequently, the feasibility of using in vivo MRI to detect magnetosonoporation/Feridex-labeled stem cells was validated in living animals and confirmed by histologic correlation. The magnetosonoporation technique is expected to be convenient, efficient, and safe for future clinical application of MRI-guided cell therapies. Magn Reson Med 63:1437,1441, 2010. © 2010 Wiley-Liss, Inc. [source] R2: Identification of renal potential progenitor/stem cells that participate in the renal regeneration processes of kidney allograft fibrosisNEPHROLOGY, Issue 6 2008JI BAO SUMMARY: Aim: Many strategies are explored to ameliorate kidney allograft tubular atrophy and interstitial fibrosis (TA/IF), but little progress has been achieved. The latest evidence suggested that CD133+ cell in kidney represent a potential multipotent adult resident stem cell population that may contribute to the renal injury repair. Here we investigate whether the CD133+ cells exist in transplanted renal and exert a growth and self-repair procedure in TA/IF. Methods: Allografts from rat kidney transplant models were harvested at 4 weeks, 8 weeks and 12 weeks post transplantation. We performed immunohistochemistry to detect the CD133+ cells and immunofluorescence to detect the co-expression of CD133 or Pax-2 with Ki-67. We furthermore analysed the E-cadherin using serial sections. Results: CD133+ cells were seldom seen in control kidney, but distributed sporadically in the cortex parenchyma along with the deterioration of TA/IF. The number of CD133+ cell increased after 4 weeks and reached the peak at 8 weeks, then decreased at 12 weeks. From 8 weeks, some new tubules expressing E-cadherin were constructed with CD133+ cells. Almost all the CD133+ cells were Ki-67-positive, but not all the Ki-67+ cells expressed CD133. The rest Ki-67+ cells almost expressed Pax-2. Conclusion: Our study reveals that when majority of the tubules are damaged, a self-repair mechanism is evoked by potential adult stem cells to compensate the renal function. Thus, potential adult resident stem cells offer a new avenue for autologous cell therapies in TA/IF. [source] Combining angiogenic gene and stem cell therapies for myocardial infarctionTHE JOURNAL OF GENE MEDICINE, Issue 9 2009Jennifer Pons Abstract Background Transplantation of stem cells from various sources into infarcted hearts has the potential to promote myocardial regeneration. However, the regenerative capacity is limited partly as a result of the low survival rate of the transplanted cells in the ischemic myocardium. In the present study, we tested the hypothesis that combining cell and angiogenic gene therapies would provide additive therapeutic effects via co-injection of bone marrow-derived mesenchymal stem cells (MSCs) with an adeno-associated viral vector (AAV), MLCVEGF, which expresses vascular endothelial growth factor (VEGF) in a cardiac-specific and hypoxia-inducible manner. Methods MSCs isolated from transgenic mice expressing green fluorescent protein and MLCVEGF packaged in AAV serotype 1 capsid were injected into mouse hearts at the border of ischemic area, immediately after occlusion of the left anterior descending coronary, individually or together. Engrafted cells were detected and quantified by real-time polymerase chain reaction and immunostaining. Angiogenesis and infarct size were analyzed on histological and immunohistochemical stained sections. Cardiac function was analyzed by echocardiography. Results We found that co-injection of AAV1-MLCVEGF with MSCs reduced cell loss. Although injection of MSCs and AAV1-MLCVEGF individually improved cardiac function and reduced infarct size, co-injection of MSC and AAV1-MLCVEGF resulted in the best improvement in cardiac function as well as the smallest infarct among all groups. Moreover, injection of AAV1-MLCVEGF induced neovasculatures. Nonetheless, injection of MSCs attracted endogenous stem cell homing and increased scar thickness. Conclusions Co-injection of MLCVEGF and MSCs in ischemic hearts can result in better cardiac function and MSC survival, compared to their individual injections, as a result of the additive effects of each therapy. Copyright © 2009 John Wiley & Sons, Ltd. [source] Engineering physiologically controlled pacemaker cells with lentiviral HCN4 gene transferTHE JOURNAL OF GENE MEDICINE, Issue 5 2008Gerard J. J. Boink Abstract Background Research on biological pacemakers for the heart has so far mainly focused on short-term gene and cell therapies. To develop a clinically relevant biological pacemaker, long-term function and incorporation of autonomic modulation are crucial. Lentiviral vectors can mediate long-term gene expression, while isoform 4 of the Hyperpolarization-activated Cyclic Nucleotide-gated channel (encoded by HCN4) contributes to pacemaker function and responds maximally to cAMP, the second messenger in autonomic modulation. Material and Methods Action potential (AP) properties and pacemaker current (If) were studied in single neonatal rat ventricular myocytes that overexpressed HCN4 after lentiviral gene transduction. Autonomic responsiveness and cycle length stability were studied using extracellular electrograms of confluent cultured monolayers. Results Perforated patch-clamp experiments demonstrated that HCN4-transduced single cardiac myocytes exhibited a 10-fold higher If than non-transduced single myocytes, along with slow diastolic depolarization, comparable to pacemaker cells of the sinoatrial node, the dominant native pacemaker. HCN4-transduced monolayers exhibited a 47% increase in beating rate, compared to controls. Upon addition of DBcAMP, HCN4-transduced monolayers had beating rates which were 54% faster than baseline and significantly more regular than controls. Conclusions Lentiviral vectors efficiently transduce cardiac myocytes and mediate functional gene expression. Because HCN4-transduced myocytes demonstrate an increase in spontaneous beating rate and responsiveness to autonomic modulation, this approach may be useful to create a biological pacemaker. Copyright © 2008 John Wiley & Sons, Ltd. [source] Future of cell and gene therapies for Parkinson's disease,ANNALS OF NEUROLOGY, Issue S2 2008Ole Isacson MD The experimental field of restorative neurology continues to advance with implantation of cells or transfer of genes to treat patients with neurological disease. Both strategies have generated a consensus that demonstrates their capacity for structural and molecular brain modification in the adult brain. However, both approaches have yet to successfully address the complexities to make such novel therapeutic modalities work in the clinic. Prior experimental cell transplantation to patients with PD utilized dissected pieces of fetal midbrain tissue, containing mixtures of cells and neuronal types, as donor cells. Stem cell and progenitor cell biology provide new opportunities for selection and development of large batches of specific therapeutic cells. This may allow for cell composition analysis and dosing to optimize the benefit to an individual patient. The biotechnology used for cell and gene therapy for treatment of neurological disease may eventually be as advanced as today's pharmaceutical drug-related design processes. Current gene therapy phase 1 safety trials for PD include the delivery of a growth factor (neurturin via the glial cell line,derived neurotrophic factor receptor) and a transmitter enzyme (glutamic acid decarboxylase and aromatic acid decarboxylase). Many new insights from cell biological and molecular studies provide opportunities to selectively express or suppress factors relevant to neuroprotection and improved function of neurons involved in PD. Future gene and cell therapies are likely to coexist with classic pharmacological therapies because their use can be tailored to individual patients' underlying disease process and need for neuroprotective or restorative interventions. Ann Neurol 2008;64 (suppl):S122,S138 [source] Microarray-based gene expression analysis as a process characterization tool to establish comparability of complex biological products: Scale-up of a whole-cell immunotherapy productBIOTECHNOLOGY & BIOENGINEERING, Issue 4 2009Min Wang Abstract Whole-cell immunotherapies and other cellular therapies have shown promising results in clinical trials. Due to the complex nature of the whole cell product and of the sometimes limited correlation of clinical potency with the proposed mechanism of action, these cellular immunotherapy products are generally not considered well characterized. Therefore, one major challenge in the product development of whole cell therapies is the ability to demonstrate comparability of product after changes in the manufacturing process. Such changes are nearly inevitable with increase in manufacturing experience leading to improved and robust processes that may have higher commercial feasibility. In order to comprehensively assess the impact of the process changes on the final product, and thus establish comparability, a matrix of characterization assays (in addition to lot release assays) assessing the various aspects of the cellular product are required. In this study, we assessed the capability of DNA-microarray-based, gene-expression analysis as a characterization tool using GVAX cancer immunotherapy cells manufactured by Cell Genesys, Inc. The GVAX immunotherapy product consists two prostate cancer cell lines (CG1940 and CG8711) engineered to secrete human GM-CSF. To demonstrate the capability of the assay, we assessed the transcriptional changes in the product when produced in the presence or absence of fetal bovine serum, and under normal and hypoxic conditions, both changes intended to stress the cell lines. We then assessed the impact of an approximately 10-fold process scale-up on the final product at the transcriptional level. These data were used to develop comparisons and statistical analyses suitable for characterizing culture reproducibility and cellular product similarity. Use of gene-expression data for process characterization proved to be a reproducible and sensitive method for detecting differences due to small or large changes in culture conditions as might be encountered in process scale-up or unanticipated bioprocess failures. Gene expression analysis demonstrated that cell products of representative lots under the same production process and at the same production scale were statistically identical. Large process changes that resulted from the artificial stress conditions used (absence of FBS and induction of hypoxia) displayed profoundly different gene expression patterns. We propose the use of simple t -test analysis in combination with the herein introduced expression ratio with mean intensity (ERMI) analysis as useful tools for process characterization by global gene expression analysis. Biotechnol. Bioeng. 2009; 104: 796,808 © 2009 Wiley Periodicals, Inc. [source] Immunostimulatory Effects of Mesenchymal Stem Cell-Derived Neurons: Implications for Stem Cell Therapy in Allogeneic TransplantationsCLINICAL AND TRANSLATIONAL SCIENCE, Issue 1 2008Marianne D. Castillo Abstract Mesenchymal stem cells (MSCs) differentiate along various lineages to specialized mesodermal cells and also transdifferentiate into cells such as ectodermal neurons. MSCs are among the leading adult stem cells for application in regenerative medicine. Advantages include their immune-suppressive properties and reduced ethical concerns. MSCs also show immune-enhancing functions. Major histocompatibility complex II (MHC-II) is expected to be downregulated in MSCs during neurogenesis. Ideally, "off the shelf" MSCs would be suited for rapid delivery into patients. The question is whether these MSC-derived neurons can reexpress MHC-II in a milieu of inflammation. Western analyses demonstrated gradual decrease in MHC-II during neurogenesis, which correlated with the expression of nuclear CIITA, the master regulator of MHC-II expression. MHC-II expression was reversed by exogenous IFNY. One-way mixed lymphocyte reaction with partly differentiated neurons showed a stimulatory effect, which was partly explained by the release of the proinflammatory neurotransmitter substance P (SP), cytokines, and decreases in miR-130a and miR-206. The anti-inflammatory neurotransmitters VIP and CGRP were decreased at the peak time of immune stimulation. In summary, MSC-derived neurons show decreased MHC-II expression, which could be reexpressed by IFNY. The release of neurotransmitters could be involved in initiating inflammation, underscoring the relevance of immune responses as consideration for stem cell therapies. [source] Hydrogels as a Platform for Stem Cell Delivery to the HeartCONGESTIVE HEART FAILURE, Issue 3 2010Mazen Kurdi PhD Stem cell therapy offers great promise to repair the injured or failing heart. The outcomes of clinical trials to date, however, have shown that the actual benefit realized falls far short of the promise. A number of factors may explain why that is the case, but poor stem cell retention and engraftment in the hostile environment of the injured heart would seem to be a major factor. Improving stem cell retention and longevity once delivered would seem a logical means to enhance their reparative function. One way to accomplish this goal may be injectable hydrogels, which would serve to fix stem cells in place while providing a sheltering environment. Hydrogels also provide a means to allow for the paracrine factors produced by encapsulated stem cells to diffuse into the injured myocardium. Alternatively, hydrogels themselves can be used for the sustained delivery of reparative factors. Here the authors discuss chitosan-based hydrogels. Congest Heart Fail. 2010;16:132,135. © 2010 Wiley Periodicals, Inc. [source] Adult bone marrow,derived stem cells for organ regeneration and repairDEVELOPMENTAL DYNAMICS, Issue 12 2007Florian Tögel Abstract Stem cells have been recognized as a potential tool for the development of innovative therapeutic strategies. There are in general two types of stem cells, embryonic and adult stem cells. While embryonic stem cell therapy has been riddled with problems of allogeneic rejection and ethical concerns, adult stem cells have long been used in the treatment of hematological malignancies. With the recognition of additional, potentially therapeutic characteristics, bone marrow,derived stem cells have become a tool in regenerative medicine. The bone marrow is an ideal source of stem cells because it is easily accessible and harbors two types of stem cells. Hematopoietic stem cells give rise to all blood cell types and have been shown to exhibit plasticity, while multipotent marrow stromal cells are the source of osteocytes, chondrocytes, and fat cells and have been shown to support and generate a large number of different cell types. This review describes the general characteristics of these stem cell populations and their current and potential future applications in regenerative medicine. Developmental Dynamics 236:3321,3331, 2007. © 2007 Wiley-Liss, Inc. [source] Neural stem cells for the treatment of disorders of the enteric nervous system: Strategies and challengesDEVELOPMENTAL DYNAMICS, Issue 1 2007Maria-Adelaide Micci Abstract The main goal of this review is to summarize the status of the research in the field of stem cells transplantation, as it is applicable to the treatment of gastrointestinal motility. This field of research has advanced tremendously in the past 10 years, and recent data produced in our laboratories as well as others is contributing to the excitement on the use of neural stem cells (NSC) as a valuable therapeutic approach for disorders of the enteric nervous system characterized by a loss of critical neuronal subpopulations. There are several sources of NSC, and here we describe therapeutic strategies for NSC transplantation in the gut. These include using NSC as a relatively nonspecific cellular replacement strategy in conditions where large populations of neurons or their subsets are missing or destroyed. As with many other recent "breakthroughs" stem cell therapy may eventually prove to be overrated. However, at the present time, it does appear to provide the hope for a true cure for many currently intractable diseases of both the central and the peripheral nervous system. Certainly more extensive research is needed in this field. We hope that our review will encourage new investigators in entering this field of research ad contribute to our knowledge of the potentials of NSC and other cells for the treatment of gastrointestinal dysmotility. Developmental Dynamics 236:33,43, 2007. © 2006 Wiley-Liss, Inc. [source] Cardiovascular cell therapy and endogenous repairDIABETES OBESITY & METABOLISM, Issue 2008D. A. Taylor Cardiovascular disease (CVD) exceeds infection and cancer as the leading cause of death. In the USA alone, approximately a million individuals suffer an acute myocardial infarction (AMI) annually. As the prevalence of CVD risk factors (e.g. hypertension, obesity and type 2 diabetes) rises, CVD is increasing in younger individuals. Fortunately, existing therapies have improved post-AMI mortality, but in turn have increased the prevalence of post-AMI heart failure (HF). Approximately half-a-million new HF cases are diagnosed each year in the USA. In the next 25 years, up to 15% of the population over the age of 65 in the USA is projected to have HF. Therapeutic interventions that prevent/reverse atherosclerosis, prevent post-AMI HF and halt the progressive functional deterioration once HF occurs are all needed. Cell therapy , either via exogenous delivery or by endogenous mobilization of cells , may be able to do so, in part, by improving the body's capacity for repair. To date, primarily bone marrow- or blood-derived cells have been utilized after AMI to prevent left ventricular dysfunction, and skeletal myoblasts have been transplanted into failing myocardium. Preclinical studies are directed at prevention/reversal of atherosclerosis with bone marrow precursors, and ultimately at replacing failing heart with a cell-based bioartificial construct. [source] ,-cell development: the role of intercellular signalsDIABETES OBESITY & METABOLISM, Issue 2008R. Scharfmann Understanding in detail how pancreatic endocrine cells develop is important for many reasons. From a scientific point of view, elucidation of such a complex process is a major challenge. From a more applied point of view, this may help us to better understand and treat specific forms of diabetes. Although a variety of therapeutic approaches are well validated, no cure for diabetes is available. Many arguments indicate that the development of new strategies to cure diabetic patients will require precise understanding of the way ,-cells form during development. This is obvious for a future cell therapy using ,-cells produced from embryonic stem cells. This also holds true for therapeutic approaches based on regenerative medicine. In this review, we summarize our current knowledge concerning pancreatic development and focus on the role of extracellular signals implicated in ,-cell development from pancreatic progenitors. [source] Progenitor cells in the adult pancreasDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2004Andrew M. Holland Abstract The ,-cell mass in the adult pancreas possesses the ability to undergo limited regeneration following injury. Identifying the progenitor cells involved in this process and understanding the mechanisms leading to their maturation will open new avenues for the treatment of type 1 diabetes. However, despite steady advances in determining the molecular basis of early pancreatic development, the identification of pancreatic stem cells or ,-cell progenitors and the molecular mechanisms underlying ,-cell regeneration remain unclear. Recent advances in the directed differentiation of embryonic and adult stem cells has heightened interest in the possible application of stem cell therapy in the treatment of type 1 diabetes. Drawing on the expanding knowledge of pancreas development, ,-cell regeneration and stem cell research, this review focuses on progenitor cells in the adult pancreas as a potential source of ,-cells. Copyright © 2004 John Wiley & Sons, Ltd. [source] Development of Live Cell Chips to Monitor Cell Differentiation ProcessesENGINEERING IN LIFE SCIENCES (ELECTRONIC), Issue 1 2008C. Maercker Abstract A big demand exists for high-throughput functional in vitro assays which can measure cellular phenotypes by molecular methods and therefore improve the resources of primary cells for cell therapy, tissue engineering and high-content screenings in drug development. This approach focuses on cellular adhesion which is an important differentiation process during homing of stem cells. Moreover, it is a promising method especially for adherent cells which are not accessible by classical cell sorting methods. The chip design includes a housing with electrodes to measure electric field densities and impedance, respectively. Moreover, specific coatings of the wells permit a perfect growth of the selected cell types. In parallel, protein biomarkers can be followed by light microscopy. So far, experiments have been started to discriminate between different cell densities and cell types. In addition, after stimulating human cardiac fibroblasts and human umbilical vein endothelial cells, concentrations of proteins involved in adhesion had been increased, and proteins were translocated within the cells. In ongoing experiments, different human cell lines and fibroblastoid mesenchymal stem cells isolated from fat tissue, umbilical cord, or bone marrow are tested in the chip. To optimize the adhesion conditions, the surfaces within the vials of the chip were specifically activated. Microscopy was adjusted to be able to measure cellular morphology in parallel. This concept allows to identify the behavior of mesenchymal stem cells, which cannot be described so far by standard biomarkers. In addition, simulation of the homing process of the cells within its stem cell niche in an in vitro assay is a promising setup for large-scale gain-of-function or loss-of-function screenings in functional genomics as well as for generating precursor cells relevant for the therapy of various diseases. [source] Mesenchymal stem cell therapy in equine musculoskeletal disease: scientific fact or clinical fiction?EQUINE VETERINARY JOURNAL, Issue 2 2007S. E. TAYLOR Summary The goal in the therapeutic use of mesenchymal stem cells (MSCs) in musculoskeletal disease is to harness the regenerative nature of these cells focussing on their potential to grow new tissues and organs to replace damaged or diseased tissue. Laboratory isolation of MSCs is now well established and has recently been demonstrated for equine MSCs. Stem cell science has attracted considerable interest in both the scientific and clinical communities because of its potential to regenerate tissues. Research into the use of MSCs in tissue regeneration in general reflects human medical needs, however, the nature, prevalence and prognosis of superficial digital flexor tendonitis has put equine veterinary science at the forefront of tendon regeneration research. Much has been investigated and learnt but it must be appreciated that in spite of this, the field is still relatively young and both communities must prepare themselves for considerable time and effort to develop the technology into a highly efficient treatments. The promise of functional tissue engineering to replace old parts with new fully justifies the interest. At present, however, it is important to balance the understanding of our current limitations with a desire to progress the technology. [source] | |||||||||||||||||||||||||||||||||||||