Use Of Adult Stem Cells Research Articles

Adult Stem Cells: Perspectives for Therapeutic Applications

The use of adult stem cells in tissue regeneration appears to be a powerful research tool, due to the intrinsic characteristics of these cells, i.e., self-renewal and unlimited capacity for proliferation. In particular, mesenchymal stem cells (MSCs) obtained from bone marrow or peripheral blood can be easily isolated, cultivated, propagated and can be differentiated into several specialized cell types thanks to their plasticity. Among these cells, MSCs can evolve into cardiac cell lineages. Since heart damage leads to the irreversible loss of cardiac function, cell transplantation could be a potential therapy for heart injury. Our laboratory has focused on the purification and expansion of rat and sheep MSCs, their differentiation into cardiomyocytes and their characterisation. Numerous results indicate that MSCs could be promising for therapy, however we need to better understand the biology of stem cells to improve methods for delivery and/or pharmacological activation. These techniques can indeed track engrafted cells and systems to guarantee their safe use.

Thinking inside the box

In the next few decades, brain medicine will present a particular socioeconomic challenge for ageing citizens worldwide. Many disorders and ailments that affect the brain—including Alzheimer disease, Parkinson disease, dementia and stroke—are chronic conditions that persist for years or even decades. In addition, many of these disorders have devastating effects, which together create a substantial burden on society: about one‐third of the global disease burden can be attributed to disorders of the brain or nervous system (Olesen & Leonardi, 2003; Andlin‐Sobocki et al , 2005). In the USA alone, there are as many as 5.5 million individuals with Alzheimer disease, 1.5 million with Parkinson disease and 400,000 with multiple sclerosis. These devastating diseases not only place a heavy emotional burden on patients and their care‐givers, but also have an important economic impact. > …about one‐third of the global disease burden can be attributed to disorders of the brain or nervous system Unfortunately, this tremendous socioeconomic problem is worsening, because the risk of suffering from a brain disease increases with age, and life expectancy is increasing worldwide, particularly in developed countries. In the case of Alzheimer disease, for example, ∼10% of US citizens aged over 65 years are affected, the prevalence rate has more than doubled since 1980 and it could increase twofold to threefold by 2050 if the current trend continues (Alzheimer's Association, 2006). Unfortunately, research has had little impact on these statistics. Despite vigorous efforts from both the pharmaceutical industry and biomedical researchers, there are still no disease‐modifying treatments available for Alzheimer disease, multiple sclerosis, stroke and a range of other neurological disorders. Some have argued that this problem cannot be solved by standard high‐throughput target‐based drug discovery methods, because we simply do not know which mechanisms to target. Instead, we should revert to previous empirical models of drug …

Review: Gene- and Stem Cell–Based Therapeutics for Bone Regeneration and Repair

Many clinical conditions require regeneration or implantation of bone. This is one focus shared by neurosurgery and orthopedics. Current therapeutic options (bone grafting and protein-based therapy) do not provide satisfying solutions to the problem of massive bone defects. In the past few years, gene- and stem cell-based therapy has been extensively studied to achieve a viable alternative to current solutions offered by modern medicine for bone-loss repair. The use of adult stem cells for bone regeneration has gained much focus. This unique population of multipotential cells has been isolated from various sources, including bone marrow, adipose, and muscle tissues. Genetic engineering of adult stem cells with potent osteogenic genes has led to fracture repair and rapid bone formation in vivo. It is hypothesized that these genetically modified cells exert both an autocrine and a paracrine effects on host stem cells, leading to an enhanced osteogenic effect. The use of direct gene delivery has also shown much promise for in vivo bone repair. Several viral and nonviral methods have been used to achieve substantial bone tissue formation in various sites in animal models. To advance these platforms to the clinical setting, it will be mandatory to overcome specific hurdles, such as control over transgene expression, viral vector toxicity, and prolonged culture periods of therapeutic stem cells. This review covers a prospect of cell and gene therapy for bone repair as well as some very recent advancements in stem cell isolation, genetic engineering, and exogenous control of transgene expression.

Recent advances into the understanding of mesenchymal stem cell trafficking

The use of adult stem cells to regenerate damaged tissue circumvents the moral and technical issues associated with the use of those from an embryonic source. Mesenchymal stem cells (MSC) can be isolated from a variety of tissues, most commonly from the bone marrow, and, although they represent a very small percentage of these cells, are easily expandable. Recently, the use of MSC has provided clinical benefit to patients with osteogenesis imperfecta, graft-versus-host disease and myocardial infarction. The cellular cues that enabled the MSC to be directed to the sites of tissue damage and the mechanisms by which MSC then exert their therapeutic effect are becoming clearer. This review discusses the relative therapeutic importance of the ability of MSC to differentiate into multiple cell lineages or stimulate resident or attracted cells via a paracrine mode of action. It also reviews recent findings that MSC home to damaged tissues in a similar, but somewhat distinct, manner to that of leucocytes via the utilisation of adhesion molecules, such as selectins and integrins, and chemokines and their receptors in a manner reminiscent of leucocytes trafficking from the blood stream to inflammatory sites.

New Insights into the Pathogenesis and Treatment of Idiopathic Pulmonary Fibrosis: A Potential Role for Stem Cells in the Lung Parenchyma and Implications for Therapy

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and often fatal form of interstitial lung disease. It is characterized by injury with loss of lung epithelial cells and abnormal tissue repair, resulting in replacement of normal functional tissue, abnormal accumulation of fibroblasts and myofibroblasts, deposition of extracellular matrix, and distortion of lung architecture which results in respiratory failure. Despite improvements in the diagnostic approach to IPF and active research in recent years, the molecular mechanisms of the disease remain poorly understood. This highly lethal lung disorder continues to pose major clinical challenges since an effective therapeutic regimen has yet to be identified and developed. For example, a treatment modality has been based on the assumption that IPF is a chronic inflammatory disease, yet most available anti-inflammatory drugs are not effective in treating it. Hence researchers are now focusing on understanding alternative underlying mechanisms involved in the pathogenesis of IPF in the hope of discovering potentially new pharmaceutical targets. This paper will focus on lung tissue repair, regeneration, remodeling, and cell types that may be important to consider in therapeutic interventions and includes a more detailed discussion of the potential targets of current therapeutic attack in pulmonary fibrosis. The discovery that adult bone marrow stem cells can contribute to the formation of differentiated cell types in other tissues, especially after injury, implies that they have the potential to participate in tissue remodeling, and perhaps regeneration. The current promise of the use of adult stem cells for tissue regeneration, and the belief that once irreversibly damaged tissue could be restored to a normal functional capacity using stem cell-based therapy, suggests a novel approach for treatment of diverse chronic diseases. However this optimism is tempered by current evidence that the pathogenesis of pulmonary fibrosis may involve the recruitment of bone marrow-derived fibroblasts, which are the key contributors to the pathogenesis of this chronic progressive disorder. Nevertheless, stem cell-related therapies are widely viewed as promising treatment options for patients suffering from various types of pulmonary diseases. Gender mismatched bone marrow or lung transplant recipients serve as natural populations in which to study the role of bone marrow-derived stem cells in recovery from pulmonary diseases. Understanding the mechanism of recruitment of stem cells to sites of injury, and their involvement in tissue repair, regeneration, and remodeling may offer a novel therapeutic target for developing more effective treatments against this fatal disorder. This article reviews the new concepts in the pathogenesis, current and future treatment options of pulmonary fibrosis, and the recent advances regarding the roles of stem cells in lung tissue repair, regeneration, and remodeling.

Regenerative Endodontics: A Review of Current Status and a Call for Action

Millions of teeth are saved each year by root canal therapy. Although current treatment modalities offer high levels of success for many conditions, an ideal form of therapy might consist of regenerative approaches in which diseased or necrotic pulp tissues are removed and replaced with healthy pulp tissue to revitalize teeth. Researchers are working toward this objective. Regenerative endodontics is the creation and delivery of tissues to replace diseased, missing, and traumatized pulp. This review provides an overview of regenerative endodontics and its goals, and describes possible techniques that will allow regenerative endodontics to become a reality. These potential approaches include root-canal revascularization, postnatal (adult) stem cell therapy, pulp implant, scaffold implant, three-dimensional cell printing, injectable scaffolds, and gene therapy. These regenerative endodontic techniques will possibly involve some combination of disinfection or debridement of infected root canal systems with apical enlargement to permit revascularization and use of adult stem cells, scaffolds, and growth factors. Although the challenges of introducing endodontic tissue engineering therapies are substantial, the potential benefits to patients and the profession are equally ground breaking. Patient demand is staggering both in scope and cost, because tissue engineering therapy offers the possibility of restoring natural function instead of surgical placement of an artificial prosthesis. By providing an overview of the methodological issues required to develop potential regenerative endodontic therapies, we hope to present a call for action to develop these therapies for clinical use.

The use of adult stem cells in rebuilding the human face

The use of adult stem cells in rebuilding the human face

An ethical analysis of alternative methods to obtain pluripotent stem cells without destroying embryos

Although few ethical concerns exist regarding the use of adult stem cells, the field of embryonic stem cell research is fraught with moral qualms. Several alternative sources of pluripotent stem cells have recently been presented that try to sidestep the destruction of human embryos. The goal of these new proposals is to avoid embryo destruction, the main objection to embryonic stem cell research and thus introduce a type of stem cell research that would gain widespread approval and support. This article suggests that most embryo-saving alternatives fail to reach this goal given the concessions they require with regard to the speed of progress, technical complexity, safety and security of applications, degree of dependence on limited resources and extent of the field of application. The second part of the article identifies and analyses the two main strategies that alternative sources of pluripotent stem cells are based on and points out their shortcomings.

Muscle regeneration by adipose tissue-derived adult stem cells attached to injectable PLGA spheres

The use of adult stem cells for cell-based tissue engineering and regeneration strategies represents a promising approach for skeletal muscle repair. We have evaluated the combination of adipose tissue-derived adult stem cells (ADSCs) obtained from autologous liposuction and injectable poly(lactic-co-glycolic acid) (PLGA) spheres for muscle regeneration. ADSCs attached to PLGA spheres and PLGA spheres alone were cultured in myogenic medium for 21 days and injected subcutaneously into the necks of nude mice. After 30 and 60 days, the mice were sacrificed, and newly formed tissues were analyzed by immunostaining, H and E staining, and RT-PCR. We found that ADSCs attached to PLGA spheres, but not PLGA spheres alone, were able to generate muscle tissue. These findings suggest that ADSCs and PLGA spheres are useful materials for muscle tissue engineering and that their combination can be used in clinical settings for muscle regeneration.

Adult stem cell homing and differentiation in vitro on composite fibrin matrix

Strategies to generate differentiated cells from haematopoetic progenitor cells will enhance potential use of adult stem cells for therapeutic transplantation or tissue engineering. Transplantation of undifferentiated stem cells into recipient tissue hinges on the hypothesis of a milieu dependent differentiation and it has been suggested that a clot-equivalent scaffold is crucial for these circulating cells to anchor and multiply. Here a natural scaffold, fibrin along with fibronectin, gelatin and growth factors has been used to induce endothelial progenitor cells and smooth muscle progenitor cells to differentiate into endothelial cells and smooth muscle cells, respectively, from peripheral blood mononuclear cells. Characteristics of endothelial cells have been verified by the detection of mRNA for and immunostaining the cells for von Willebrand factor, uptake of acetylated low-density lipoproteins and measurement of released nitric oxide in the culture medium, as nitrite. The specific molecules that characterized smooth muscle cells were alpha smooth muscle actin and calponin, besides deposition of collagen type I and elastin, onto the culture matrix. The adhesive proteins used for the fabrication of endothelial progenitor cells matrix and smooth muscle progenitor cells matrix were the same, but specific differentiation was brought about by modulating the growth factor composition in the matrix and in the culture medium. Both endothelial and smooth muscle cells were consistently developed from 20 ml of human blood.

Fetal and adult liver stem cells for liver regeneration and tissue engineering

For the development of innovative cell-based liver directed therapies, e.g. liver tissue engineering, the use of stem cells might be very attractive to overcome the limitation of donor liver tissue. Liver specific differentiation of embryonic, fetal or adult stem cells is currently under investigation. Different types of fetal liver (stem) cells during development were identified, and their advantageous growth potential and bipotential differentiation capacity were shown. However, ethical and legal issues have to be addressed before using fetal cells. Use of adult stem cells is clinically established, e.g. transplantation of hematopoietic stem cells. Other bone marrow derived liver stem cells might be mesenchymal stem cells (MSC). However, the transdifferentiation potential is still in question due to the observation of cellular fusion in several in vivo experiments. In vitro experiments revealed a crucial role of the environment (e.g. growth factors and extracellular matrix) for specific differentiation of stem cells. Co-cultured liver cells also seemed to be important for hepatic gene expression of MSC. For successful liver cell transplantation, a novel approach of tissue engineering by orthotopic transplantation of gel-immobilized cells could be promising, providing optimal environment for the injected cells. Moreover, an orthotopic tissue engineering approach using bipotential stem cells could lead to a repopulation of the recipients liver with healthy liver and biliary cells, thus providing both hepatic functions and biliary excretion. Future studies have to investigate, which stem cell and environmental conditions would be most suitable for the use of stem cells for liver regeneration or tissue engineering approaches.

The use of adult stem cells in rebuilding the human face

Stem cells have been isolated from a variety of embryonic and postnatal (adult) tissues, including bone marrow. Bone marrow stromal cells (BMSCs), which are non-blood-forming cells in marrow, contain a subset of skeletal stem cells (SSCs) that are able to regenerate all types of skeletal tissue: bone, cartilage, blood-supportive stromal cells and marrow fat cells. Bone marrow suspensions are placed into culture for analysis of their biological character and for expansion of their number. The resulting populations of cells are used in a variety of assays to establish the existence of an adult SSC, and the ability of BMSC populations to regenerate hard tissues in the craniofacial region, in conjunction with appropriate scaffolds. Single-cell analysis established the existence of a true adult SSC in bone marrow. Populations of ex vivo expanded BMSCs (a subset of which are SSCs) are able to regenerate a bone/marrow organ. In conjunction with appropriate scaffolds, these cells can be used to regenerate bone in a variety of applications. BMSCs have the potential to re-create tissues of the craniofacial region to restore normal structure and function in reconstructing the hard tissues of a face. Ex vivo expanded BMSCs with scaffolds have been used in a limited number of patients to date, but likely will be used more extensively in the near future.

Attempts to Recruit Stem Cells for Repair of Acute Myocardial Infarction

EXPERIMENTAL STUDIES SUGGEST THAT MOST OF THE myocardial cells destined to die following an acute coronary artery occlusion will do so within 3 to 6 hours. Early coronary reperfusion with thrombolytic therapy, angioplasty, and/or stenting can certainly salvage ischemic myocardium and improve clinical outcome but late reperfusion will not salvage myocardium. However, there are therapies for which strong evidence has demonstrated benefit even when started beyond 24 hours. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers reduce the risk of heart failure and premature death, presumably by decreasing progressive left ventricular dilatation and remodeling. Other established and effective adjunctive therapies include antiplatelet agents and statins. A relatively new and exciting concept for late treatment of acute myocardial infarction (AMI) is that the thin, noncontractile collagenous scar that results after myocyte death could be replaced by viable, contracting myocardium (ie, the damaged heart can be rebuilt). Early work by several groups showed the feasibility of implanting immature cells such as neonatal or fetal cardiomyocytes or skeletal myoblasts into normal or infarcted myocardium. Using a rat model of myocardial infarction (MI), our research group observed that direct injection of either neonatal or fetal cardiomyocytes 1 week after coronary artery occlusion yielded well-delineated grafts of muscle, which thickened the thin wall of the infarct scar, improved left ventricular ejection fraction, developed a blood supply, and survived for a long period. Unfortunately, use of neonatal or fetal cardiomyocytes is limited by low availability, which has in part stimulated interest in the use of adult stem cells. There has been a virtual explosion of research into the use of stem cells to replace infarcted myocardium over the past 5 years. Adult stem cells derived from bone marrow, adipose tissue, and cardiac tissue have been studied; as have embryonic stem cells. Controversy continues regarding whether adult hematopoeitic stem cells derived from bone marrow do indeed truly transdifferentiate into cardiac tissue. Several small clinical trials have suggested that therapies such as peripheral blood–derived or bone marrow–derived stem cells improve cardiac function after MI. Techniques to deliver these cells include direct intramyocardial injection and intracoronary injection. Another approach to rebuilding myocardial scar tissue is to recruit stem cells to the site of injury (also referred to as homing) with various cytokines such as granulocyte colony-stimulating factor (G-CSF) and stem cell factor. The concept is that these proteins, usually administered intravenously, recruit bone marrow–derived progenitor cells that then target damaged tissue. Several clinical studies using G-CSF in AMI patients suggest improvement in left ventricular function. These studies as well as positive studies using adult stem cells have led to tremendous enthusiasm and hype. While small trials are initially needed to establish safety and feasibility, many of the trials examining the use of stem cells for cardiovascular disease treatment have limitations that make interpretation of efficacy difficult. These include lack of controls, proper randomization, and blinding; lack of systematic assessment of infarct size or left ventricular function prior to administration of therapy; short-term duration; and small numbers of patients (usually between 5 and 50). One common problem with some of the uncontrolled trials that have used either cells or protein is the assumption that an improvement in regional and global left ventricular function that occurred over time following coronary reperfusion for AMI was due to the therapy. Studies performed in the late 1970s and in the early 1980s showed that the return of function in the salvaged, viable, postischemic myocardium overlying the infarct could occur naturally following reperfusion of an occluded coronary artery but that this recovery required days to weeks. Recovery of this stunned myocardium should not be interpreted as a treatment effect due to cell injection or pharmacological cell recruitment.

Human Umbilical Cord Blood–Derived CD133+ Cells Enhance Function and Repair of the Infarcted Myocardium

The use of adult stem cells for myocardial tissue repair might be limited in elderly and sick people because their cells are depleted and exhausted. The present study was conducted to explore the potential of human umbilical cord blood (UCB) CD133+ progenitor cells for myocardial tissue repair in a model of extensive myocardial infarction (MI). CD133+ progenitor cells were isolated from newborn UCB. Cells (1.2-2 x 10(6)) or saline (control) was infused intravenously 7 days after permanent coronary artery ligation in athymic nude rats. Left ventricular (LV) function was assessed before and 1 month after infusion by echocardiography. Tracking of human cells was performed by fluorescent in situ hybridization for human X and Y chromosomes or by immunostaining for HLA-DR or HLA-ABC. One month after delivery, LV fractional shortening improved by 42 +/- 17% in cell-treated hearts and decreased by 39 +/- 10% in controls (p = .001). Anterior wall thickness decreased significantly in controls but not in treated hearts. Microscopic examination revealed that the UCB cells were able to migrate, colonize, and survive in the infarcted myocardium. Human cells were identified near vessel walls and LV cavity and were occasionally incorporated into endothelial cells in six of nine cell-treated animals but not in controls. Scar tissue from cell-treated animals was significantly populated with autologous myofibroblasts as indicated by colocalization of HLA-DR and alpha-smooth muscle actin staining. In conclusion, the present work suggests that, after MI, intravenous delivery of human UCB-derived CD133+ cells can produce functional recovery by preventing scar thinning and LV systolic dilatation.

Adult-derived stem cells and their potential for use in tissue repair and molecular medicine.

This report reviews three categories of precursor cells present within adults. The first category of precursor cell, the epiblast-like stem cell, has the potential of forming cells from all three embryonic germ layer lineages, e.g., ectoderm, mesoderm, and endoderm. The second category of precursor cell, the germ layer lineage stem cell, consists of three separate cells. Each of the three cells is committed to form cells limited to a specific embryonic germ layer lineage. Thus the second category consists of germ layer lineage ectodermal stem cells, germ layer lineage mesodermal stem cells, and germ layer lineage endodermal stem cells. The third category of precursor cells, progenitor cells, contains a multitude of cells. These cells are committed to form specific cell and tissue types and are the immediate precursors to the differentiated cells and tissues of the adult. The three categories of precursor cells can be readily isolated from adult tissues. They can be distinguished from each other based on their size, growth in cell culture, expressed genes, cell surface markers, and potential for differentiation. This report also discusses new findings. These findings include the karyotypic analysis of germ layer lineage stem cells; the appearance of dopaminergic neurons after implantation of naive adult pluripotent stem cells into a 6-hydroxydopamine-lesioned Parkinson's model; and the use of adult stem cells as transport mechanisms for exogenous genetic material. We conclude by discussing the potential roles of adult-derived precursor cells as building blocks for tissue repair and as delivery vehicles for molecular medicine.

Regenerative medicine of the pancreatic β cells

Diabetes mellitus is a metabolic disorder that affects millions of people. The number of patients suffering from diabetes continues to increase all over the world. Both type 1 and type 2 diabetes result from an inadequate mass of functioning beta cells. To achieve the ultimate goal of curing diabetes in the future, the mechanism of the regenerative process of the adult human pancreas must be elucidated. In this review, we first summarize the regenerative processes of the pancreas observed in animal models in vivo, and approaches to promote the regeneration of the pancreas in vivo. Next we consider other new approaches, such as stem cell research and cell-based therapy, for the cure of diabetes in the future. Based on the innovative success of the Edmonton protocol, islet transplantation has been considered to be a new therapeutic option for the treatment of diabetes. However, a serious shortage of donor pancreata is a critical problem. We suggest that the following issues should be solved in order to realize cell-based therapy. The first is to establish a source of stem/progenitor cells that will multiply easily in vitro and maintain their property as progenitor cells. The probable use of adult stem cells will circumvent potential ethical problems, and autotransplantation will become possible. The most difficult and as yet unsolved issue is how to differentiate these cells and acquire fully functional islets. Further investigations to understand the regenerative process of the adult pancreas and the appropriate induction of stem cell differentiation will help to establish cell-based therapy in diabetes.

Epithelial Stem Cells and Their Niche: There's No Place Like Home

Stem cells hold the promise of novel therapy for treating diseases. Unfortunately, the use and study of embryonic stem cells are currently clouded by ethical controversy. Adult stem cells offer a unique alternative in that they may be isolated, studied, or manipulated without harming the donor. Currently, several obstacles for use of adult stem cells as therapy exist. First, the ability to identify most adult stem cells is impeded by lack of stem cell markers. Second, in vitro systems for manipulating adult stem cell populations are often not well defined. Finally, our understanding of how adult stem cells are regulated within their niche is in its infancy. Next to the hematopoietic stem cell, epithelial stem cells are one of the most widely studied stem cell populations. Even so, the diversity between epithelial functions in different organs makes it difficult to determine whether common themes exist in regulating these related stem cells. Although each epithelial stem cell niche possesses unique features to facilitate its specialized functionality, they likely share many common aspects of regulation. The purpose of this review is to compare how the cell signaling influences the stem cell and its niche in rapidly self-renewing epithelia.

Multipotential differentiation of adipose tissue-derived stem cells

Tissue engineering offers considerable promise in the repair or replacement of diseased and/or damaged tissues. The cellular component of this regenerative approach will play a key role in bringing these tissue engineered constructs from the laboratory bench to the clinical bedside. However, the ideal source of cells still remains unclear and may differ depending upon the application. Current research for many applications is focused on the use of adult stem cells. The properties of adult stem cells that make them well-suited for regenerative medicine are (1) ease of harvest for autologous transplantation, (2) high proliferation rates for ex vivo expansion and (3) multilineage differentiation capacity. This review will highlight the use of adipose tissue as a reservoir of adult stem cells and draw conclusions based upon comparisons with bone marrow stromal cells.

Side population/ABCG2-positive cells represent a heterogeneous group of haemopoietic cells: implications for the use of adult stem cells in transplantation and plasticity protocols

Murine side population (SP) cells may have an increased ability to engraft lethally irradiated mice and lack CD34 expression. Strategies using CD34 as a primary marker of haemopoietic stem cells may therefore result in the exclusion of a primitive stem cell population. The molecular basis for the murine SP phenotype has been attributed to the multidrug-resistance transporter ABCG2. This study aimed to investigate ABCG2 expression from a variety of human sources and investigate the relationship between ABCG2 expression, the SP phenotype, and expression of markers such as CD34 and CD133. SP cells were observed in different haemopoietic sources, but a significant increase in the number of SP cells was observed in PB following granulocyte colony-stimulating factor mobilisation. No direct correlation between the frequency of SP cells and the expression of ABCG2 was observed. SP cells were identified in both lineage-positive and lineage-negative population and ABCG2 expression was enriched in lineage-negative SP cells. Lineage-negative SP cells were devoid of CD34 expression but enriched for CD133. Subsequent analysis revealed that ABCG2 and CD133 are coexpressed. Together, these data suggest that the ABCG2 transporter is neither required nor responsible for the SP phenotpye in many human blood cells.

Routes to regenerating islet cells: stem cells and other biological therapies for type 1 diabetes

New biological therapies for type 1 diabetes are emerging from the forefront of stem cell and islet cell biology. Basic research in animal models has uncovered a variety of mechanisms by which natural regeneration of pancreatic islet cells occurs, despite the underlying autoimmune defect. Two mechanisms - in particular, beta-islet cell proliferation and stem cell differentiation - can be harnessed in innovative ways in order to regenerate islets lost to disease. This review provides a background on stem cells and describes a range of potential biological therapies for type 1 diabetes, including the use of adult stem cells from the spleen, an organ not previously considered a source of pancreatic stem cells. Stem cells of the spleen have been demonstrated to home to the pancreas, where they mature into fully functional islet cells responsible for restoring normoglycemia. If the underlying autoimmune defect can be eradicated, stem cells of the spleen, as well as related strategies, can be used in order to regrow islets destroyed by type 1 diabetes.