Advancing diabetes management: Exploring pancreatic beta-cell restoration’s potential and challenges

New therapeutic approaches to type 1 diabetes: from prevention to cellular or gene therapies.

In recent years, cell-based therapies have gained great enthusiasm as a new therapeutic ap- proach for addressing many disorders. Many researchers have shown the roles of stem cells in replac- ing damaged tissues and in providing extracellular factors that can promote endogenous cellular re- plenishment. Also, stem cells are rich source of soluble factors and microvesicles, which are released from their surfaces and thereby exerting paracrine effect. Although pluripotent stem cells are considered the cornerstone in regenerative medicine, various types of more differentiated adult stem and progenitor cells are exploited. In this review, we provide an overview about the recent advances in the field of regenerative medicine and stem cell therapies for diabe- tes, cardiovascular and neurodegenerative diseases, with special interest in the recent patents. Patents from WIPO, USPTO, Patent scope and European patent databases have been discussed. In conclusion, the increasing number of patents and the extensive scientific research suggests that stem cell therapies hold a promising future for the management of in- curable diseases.

Type 1 diabetes (T1D) is a deficiency in insulin production which is mainly due to loss of ?-cell pancreatic islets. Patients with T1D need to be given exogenous insulin regularly. While improvements in the delivery of insulin and glucose monitoring methods have been effective in improving patient safety, insulin therapy is not a cure and is often associated with complications and debilitating hypoglycaemic episodes. Meanwhile, pancreas or islet transplantation as a gold standard only promises temporary freedom from exogenous insulin and suffers from issues of its own. Stem cell therapy may provide a more permanent solution, given stem cells’ immunomodulatory characteristics and ability to self-renew and distinguish into specific cells. In this sense, the therapeutic potentials of stem cells are addressed in this study. These stem cells cover a wide range of treatments for T1D including embryonic stem cells, induced pluripotent stem cells, bone-marrow derived hematopoietic stem cells and multipotent mesenchymal stromal cells. The challenges faced by the current stem cell transplant in T1D treatment and Islamic viewpoints regarding ethics in stem cell research and therapy are also discussed. In conclusion, stem cell therapy offers a safe and efficient alternative treatment for T1D. However, besides the fatwa from Fatwa Committee of Selangor, the lack of Malaysian stem cells ethics should be further addressed.

Type 1 diabetes (T1D) is a deficiency in insulin production which is mainly due to loss of ?-cell pancreatic islets. Patients with T1D need to be given exogenous insulin regularly. While improvements in the delivery of insulin and glucose monitoring methods have been effective in improving patient safety, insulin therapy is not a cure and is often associated with complications and debilitating hypoglycaemic episodes. Meanwhile, pancreas or islet transplantation as a gold standard only promises temporary freedom from exogenous insulin and suffers from issues of its own. Stem cell therapy may provide a more permanent solution, given stem cells’ immunomodulatory characteristics and ability to self-renew and distinguish into specific cells. In this sense, the therapeutic potentials of stem cells are addressed in this study. These stem cells cover a wide range of treatments for T1D including embryonic stem cells, induced pluripotent stem cells, bone-marrow derived hematopoietic stem cells and multipotent mesenchymal stromal cells. The challenges faced by the current stem cell transplant in T1D treatment and Islamic viewpoints regarding ethics in stem cell research and therapy are also discussed. In conclusion, stem cell therapy offers a safe and efficient alternative treatment for T1D. However, besides the fatwa from Fatwa Committee of Selangor, the lack of Malaysian stem cells ethics should be further addressed.

Diabetes is the result of the insufficiency or dysfunction of pancreatic beta cells alone or in combination with insulin resistance. The replacement or regeneration of beta cells can effectively reverse diabetes in humans and rodents. Therefore, the identification of novel small molecules that promote pancreatic beta-cell proliferation is an attractive approach for diabetic therapy. While numerous hormones, small molecules, and growth factors are able to drive rodent beta cells to replicate, only a few small molecules have demonstrated the ability to stimulate human beta-cell proliferation. Hence, there is an urgent need for therapeutic agents that induce regeneration and expansion of adult human beta cells. Here, we describe a detailed protocol for coating chamber slides, culturing primary islets, performing islet cell disassociation, seeding cells on chamber slides, treating islet cells with compounds or infecting them with adenovirus, immunostaining of proliferation markers and imaging, and data analysis.

Highlights from the Literature

Veterinarians and veterinary medicine have been integral to the development of stem cell therapies. The contributions of large animal experimental models to the development and refinement of modern hematopoietic stem cell transplantation were noted nearly five decades ago. More recent advances in adult stem cell/regenerative cell therapies continue to expand knowledge of the basic biology and clinical applications of stem cells. A relatively liberal legal and ethical regulation of stem cell research in veterinary medicine has facilitated the development and in some instances clinical translation of a variety of cell‐based therapies involving hematopoietic stem cells and mesenchymal stem cells, as well as other adult regenerative cells and recently embryonic stem cells and induced pluripotent stem cells. In fact, many of the pioneering developments in these fields of stem cell research have been achieved through collaborations of veterinary and human scientists. This review aims to provide an overview of the contribution of large animal veterinary models in advancing stem cell therapies for both human and clinical veterinary applications. Moreover, in the context of the “One Health Initiative,” the role veterinary patients may play in the future evolution of stem cell therapies for both human and animal patients will be explored.

Introduction Regenerative medicine has become a light at the end of the tunnel for countless patients who have suffered from diseases previously considered incurable. Stem cell therapy is central to this revolutionary progress and has already made huge advances in recent years. Stem cells have the potential to regenerate tissues, repair organs, and even modulate immune responses, making them a key to delivering innovative treatments for a broad spectrum of medical conditions. This editorial describes recent progress in stem cell therapy as well as its promise as a regenerative medicine[1]. Stem Cells have unique Properties. Stem cells have unique properties that make them of great value in therapeutic applications. This allows them to self-renew and differentiate into specialized cell types with immense possibilities of being used in treating degenerative diseases, tissue injuries, and even genetic disorders. Each type is classified broadly into embryonic stem cells (ESCs), adult stem cells (ASCs), and induced pluripotent stem cells (iPSCs) with particular advantages. For example, ESCs are pluripotent and can differentiate into almost any cell type, while the more accessible and less ethically controversial MSCs like the ASCs[2]. Pioneered most recently by Shinya Yamanaka, recent breakthroughs in iPSC technology have further revolutionized the field. IpsCs overcome many of the limitations of ESCs by reprogramming somatic cells into a pluripotent state. It has accelerated the development of patient-specific therapies – personalized regenerative solutions[3]. Stem Cell Therapy Success Stories Stem cell therapies have already had tremendous success in treating multiple different medical conditions. Therapies have also been shown to be effective in treating Parkinson’s disease, spinal cord injuries, and stroke in neurological disorders. Damaged neurons have been replaced with transplanted stem cells and lost functions have been restored[4]. While recent clinical trials using MSCs and iPSCs for stroke recovery have revealed improved motor function as well as reduced inflammation, they represent a great leap forward in this field. Repairing damaged heart tissue that results from myocardial infarction has been explored using cardiomyocyte transplantation from ESCs and iPSCs. In preclinical and clinical studies, these therapies not only support tissue regeneration but also enhance cardiac function and survival outcomes[5]. The differentiation of ESCs and iPSCs into insulin-secreting β cells for use in the treatment of type- 1 diabetes represents another major milestone in stem cell therapy. But β cells transplanted into the bloodstream can regulate blood glucose levels, and at last, this represents a realistic prospect of a cure[6, 7]. Unfortunately, hematopoietic stem cell transplantation (HSCT) remains the gold standard for treating blood-related disorders, such as leukemia, aplastic anemia, and immune deficiencies. HSCT has been further made safer and more effective by advances in gene editing technologies such as CRISPR-Cas9, which now allow for targeted genetic therapies. MSCs are being widely investigated in the orthopedic field for their potential to regenerate cartilage, bone, and muscle tissue. Stem cell therapy has shown a lot of promise in osteoarthritis, fractures, and tendon injuries, where the therapies help to speed up healing and reduce pain[8]. Challenges of Stem Cell Therapy Sure, the promise of stem cell therapy is undeniable, but a host of challenges must be overcome first to make it a mainstream clinical tool. Despite all of this, safety concerns remain paramount: tumorigenesis, immune rejection, and unintended differentiation. Equally important is standardization and regulation, which will help develop consistent protocols for stem cell isolation, culture, and transplantation with reproducible outcomes from clinical trials. In addition, stem cell therapies are very expensive, which limits access, especially in low and middle-income countries. However, ESCs have continued to raise ethical concerns, particularly in the area of ESCs, and therefore alternative sources such as iPSCs and adult stem cells are needed[9]. Future Directions Overcoming these challenges is a future challenge for bioengineering, nanotechnology, and gene editing. For example, 3D bio-printed tissues and organoids bring together stem cell technology and tissue engineering to provide functional tissues for transplantation. These innovations could change the way we deal with organ failure and more advanced medical conditions[10]. Conclusion Stem cell therapy enters into a new era of progressive continuous progress. With the continued expansion of clinical trials and increasing technology, stem cell therapies have the potential to transform the treatment landscape for many diseases and injuries. Still, there is plenty of work to be done, but the convergence of interdisciplinary innovations presents a strong foundation for hope. With the participation of scientists, clinicians, policymakers, and industry stakeholders, stem cell research can be translated into safe, effective, and accessible therapies benefiting millions of patients with the possibility to recover and improve their quality of life. Regenerative medicine has a promising future and stem cells are at the center of that progress. Through innovation and addressing current challenges, we can unleash the full power of stem cell therapies to provide transformative solutions to patients around the world.

Stem cells therapy for diabetes: from past to future

Diabetes is one of the most leading cause of death worldwide. Around 40 million diabetics are reported in India. Stem cell therapy is a branch of medicine that involves introducing stem cells into a diseased tissue which triggers the body’s ability to heal itself. Stem cell therapy is a latest technique which can be used to treat diabetes mellitus. In India the success rate of stem cell therapy in diabetes mellitus is approximately 70 - 80 %. As this stem cells may be harvested from the bone marrow, umbilical cord and matured adult. In the present review we are discussing about the use of stem cell therapy in type 2 diabetes and how it works. Type 2 diabetes mellitus results from combination of insulin resistance and dysfunction of insulin producing beta cells which cannot be reversed by existing therapeutic strategies, transplantation of stem cells which are differentiating into insulin producing cells is one of the most promising strategy for treating type 2 diabetes.

When Inner Ear Stem Cell Therapy Becomes a Reality

To the Editor: The molecular mechanisms and the control of smooth muscle cell (SMC) differentiation have been extensively investigated because of its therapeutic potential.1 To date, different cell types have been used to study SMC differentiation, including a variety of mouse embryonic stem cells,2 adult stem cells,3,4 and others.5 Because several fundamental differences exist between mouse and human embryonic development,6 lack of a good model system to study human SMC differentiation has hampered the progress of translating SMC knowledge to novel clinical therapies. Human embryonic stem (hES) cells provide a valuable source of cells for studying human cell differentiation and developing therapeutic potentials in regenerative medicine. Since the initial report describing the derivation of hES cells,7 a variety of studies have established in vitro differentiation strategies to several lineages. Recently, it has been demonstrated that vascular progenitors derived from hES cells could be differentiated into endothelial cells and SMCs by endothelial …

ground: Type 1 diabetes is the result of an autoimmune attack against the insulin-producing beta cells of the pancreas. Current treatment for patients with type 1 diabetes typically involves a rigorous and invasive regimen of testing blood glucose levels many times a day along with injections of recombinant insulin. Many recent researches have shown that stem cell therapy can be the best choice for treatment of this disease. The aims of this research were investigating regeneration of pancreatic beta cells of type 1 diabetic rabbits after stem cell transplantation. Materials and Methods: 32 rabbits weighting an average of (2.5 - 3 kg) were used in this experimental study, and divided into 2 groups as follows; group A ( contains 16 controlled diabetic rabbits received insulin as a treatment ) and group B ( contains 16 diabetic rabbits received autologous mesenchymal stem cells as a treatment).The induction of diabetes was achieved by a single dose of intravenous injection of the Alloxan, which was administered to the rabbits via the marginal ear vein, mesenchymal stem cells were differentiated into insulin - producing cells and reimplanted into the rabbits of group B with daily monitoring of blood glucose level and body weight. Results: The insulin - producing cells regulated the hyperglycemia resulted from diabetic rabbits , 7 to 9 days after reimplantation the blood glucose level were decreased from about( 400 mg/dl into 180 mg/dl). Conclusions: Islet-like functional cells can be differentiate d from bone-marrow mesenchymal stem cells (MSCs), which may be a new procedure for clinical diabetes stem -cell therapy, these cells controlled blood glucose level in diabetic rabbits as the effect of insulin. MSCs play an important role in diabetes therapy by islet differentiation and

The UK stem cell bank: Creating safe stem cell lines and public support?

Human stromal (mesenchymal) stem cells (hMSC) represent a group of non-hematopoietic stem cells present in the bone marrow stroma and the stroma of other organs including subcutaneous adipose tissue, placenta, and muscles. They exhibit the characteristics of somatic stem cells of self-renewal and multi-lineage differentiation into mesoderm-type of cells, e.g., to osteoblasts, adipocytes, chondrocytes and possibly other cell types including hepatocytes and astrocytes. Due to their ease of culture and multipotentiality, hMSC are increasingly employed as a source for cells suitable for a number of clinical applications, e.g., non-healing bone fractures and defects and also non-skeletal degenerative diseases like heart failure. Currently, the numbers of clinical trials that employ MSC are increasing. However, several biological and biotechnological challenges need to be overcome to benefit from the full potential of hMSC. In this current review, we present some of the most important and recent advances in understanding of the biology of hMSC and their current and potential use in therapy.