encapsulated beta cell therapy

Type 1 diabetes (T1D) occurs as a consequence of the autoimmune destruction of insulin-producing pancreatic beta (β) cells and commonly presents with insulin deficiency and unregulated glycemic control. Despite improvements in the medical management of T1D, life-threatening complications are still common. Beta-cell replication to replace lost cells may be achieved by using small-molecule mitogenic drugs, like harmine. However, the safe and effective delivery of such drugs to beta cells remains a challenge...

Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults and despite recent advances in treatment modalities, GBM remains incurable. Injectable hydrogel scaffolds are a versatile delivery system that can improve delivery of drug and cell therapeutics for GBM. In this report, we investigated an injectable nanocellulose/chitosan-based hydrogel scaffold for neural stem cell encapsulation and delivery. Hydrogels were prepared using thermogelling beta-glycerophosphate (BGP) and hydroxyethyl cellulose (HEC), chitosan (CS), and cellulose nanocrystals (CNCs)...

Therapeutic nucleic acids are an emerging class of therapy for treating various diseases through immunomodulation, protein replacement, gene editing, and genetic engineering; but, they require a vector for safe and effective delivery to the target cells. Most gene and cell therapies rely on ex vivo gene delivery, which is laborious, time-consuming, and costly; therefore, devising a systematic vector for effective and safe in vivo delivery of therapeutic nucleic acids is required to target the cells of interest precisely...

Type 1 diabetes is a disease resulting from autoimmune destruction of the insulin-producing beta cells in the pancreas. When type 1 diabetes develops into severe secondary complications, in particular end-stage nephropathy, or life-threatening severe hypoglycemia, the best therapeutic approach is pancreas transplantation, or more recently transplantation of the pancreatic islets of Langerhans. Islet transplantation is a cell therapy procedure, that is minimally invasive and has a low morbidity, but does not display the same rate of functional success as the more invasive pancreas transplantation because of suboptimal engraftment and survival...

Despite the efforts of the pharmaceutical and research sectors, Alzheimer's disease (AD) remains incurable, imposing the demand for new effective strategies. Vitamin B12 (VB12) has aroused interest due to its in vitro anti-amyloidogenic properties. However, the high molecular weight and hydrophilicity of VB12 are the main obstacles to its clinical application by hindering its passage through the blood-brain barrier (BBB). In recent years, drug delivery systems (DDSs) capable of transporting molecules across the BBB have gained attention for their effective brain delivery...

Human embryonic stem cells (hESCs) provide opportunities for cell replacement therapy of insulin-dependent diabetes. Therapeutic quantities of human stem cell-derived islets (SC-islets) can be produced by directed differentiation. However, preventing allo-rejection and recurring autoimmunity, without the use of encapsulation or systemic immunosuppressants, remains a challenge. An attractive approach is to transplant SC-islets, genetically modified to reduce the impact of immune rejection. To determine the underlying forces that drive immunogenicity of SC-islets in inflammatory environments, we performed single-cell RNA sequencing (scRNA-seq) and whole-genome CRISPR screen of SC-islets under immune interaction with allogeneic peripheral blood mononuclear cells (PBMCs)...

There is no cure yet available for Alzheimer's disease (AD). We recently optimized encapsulated cell biodelivery (ECB) devices releasing human mature nerve growth factor (hmNGF), termed ECB-NGF, to the basal forebrain of AD patients. The ECB-NGF delivery resulted in increased CSF cholinergic markers, improved glucose metabolism, and positive effects on cognition in AD patients. However, some ECB-NGF implants showed altered hmNGF release post-explantation. To optimize the ECB-NGF platform for future therapeutic purposes, we initiated in-vitro optimization studies by exposing ECB-NGF devices to physiological factors present within the AD brain...

The emergence of multidrug-resistant (MDR) bacterial pathogens in farm animals and their zoonotic spread is a concern to both animal agriculture and public health. Apart from antimicrobial resistance (AMR), bacterial pathogens from the genera of Salmonella and Staphylococcus take refuge inside host cells, thereby demanding intervention strategies that can eliminate intracellular MDR pathogens. In this study, seven clinical isolates of Salmonella and Staphylococcus from swine farms were characterized for antibiotic (n = 24) resistance, resistance mechanisms, and virulence characteristics...

Great advances in type 1 diabetes (T1D) and type 2 diabetes (T2D) treatment have been made to this day. However, modern diabetes therapy based on insulin injections and cadaveric islets transplantation has many disadvantages. That is why researchers are developing new methods to regenerate the pancreatic hormone-producing cells in vitro. The most promising approach is the generation of stem cell-derived beta cells that could provide an unlimited source of insulin-secreting cells. Recent studies provide methods to produce beta-like cell clusters that display glucose-stimulated insulin secretion-one of the key characteristics of the beta cell...

There is a current lack of fully efficient therapies for diabetes mellitus, a chronic disease where the metabolism of blood glucose is severely hindered by a deficit in insulin or cell resistance to this hormone. Therefore, it is crucial to develop new therapeutic strategies to treat this disease, including devices for the controlled delivery of insulin or encapsulation of insulin-producing cells. In this work, fucoidan (Fu) - a marine sulfated polysaccharide exhibiting relevant properties on reducing blood glucose and antioxidant and anti-inflammatory effects - was used for the development of versatile carriers envisaging diabetes advanced therapies...

BACKGROUND AND AIMS: Wilson's disease (WD) is an inherited disorder of copper metabolism with predominant hepatic manifestations. Left untreated, it can be fatal. Current therapies focus on treating copper overload rather than targeting the pathophysiology of copper-induced liver injuries. We sought to investigate whether liposome-encapsulated curcumin (LEC) could attenuate the underlying pathophysiology of WD in a mouse model of WD. APPROACH AND RESULTS: Subcutaneous administration in a WD mouse model with ATP7B knockout (Atp7b-/- ) resulted in robust delivery of LEC to the liver as determined by in-vitro and in-vivo imaging...

Bioengineered pancreatic β-islets have been widely advocated for the research and treatment of diabetes by offering both suitable cell culture models for the study of the pathology and the testing of new drugs and a therapy in those patients no longer responding to insulin administration and as an alternative to the shortage of donors for organ and islet transplantation. Unlike most of the studies published so far where pancreatic islets of pancreatic β-cells are encapsulated in hydrogels, this study demonstrate the formation of bioengineered pancreatic islets through cell anchoring to a gelatine-based biomaterial, PhenoDrive-Y, able to mimic the basement membrane of tissues...

Amyloid-beta (Aβ) aggregates deposition at extra neuronal sites induces neurotoxicity and major hallmarks of Alzheimer's disease (AD). To reduce the Aβ fibril toxicity, multi-functional polyamidoamine (PAMAM) dendrimer was conjugated with tocopheryl polyethylene glycol succinate-1000 (TPGS) which acts as a carrier matrix for the delivery of neuroprotective molecule piperine (PIP). This PIP-TPGS-PAMAM dendrimer was fabricated to mitigate the Aβ1-42 fibril toxicity on SHSY5Y cells. TPGS-PAMAM was fabricated through carbodiimide coupling reaction, and PIP was encapsulated in dendrimer through solvent injection method to prepare PIP-TPGS-PAMAM...

Antimicrobial resistance is one of the greatest global threats. Particularly, multidrug resistant extended-spectrum β-lactamase (ESBL)-producing pathogens confer resistance to many commonly used medically important antibiotics, especially beta-lactam antibiotics. Here, we developed an innovative combination approach to therapy for multidrug resistant pathogens by encapsulating cephalosporin antibiotics and β-lactamase inhibitors with chitosan nanoparticles (CNAIs). The four combinations of CNAIs including two cephalosporin antibiotics (cefotaxime and ceftiofur) with two β-lactamase inhibitors (tazobactam and clavulanate) were engineered as water-oil-water emulsions...

Encapsulation and transplantation of insulin-producing cells offer a promising curative treatment for type 1 diabetes (T1D) without immunosuppression. However, biomaterials used to encapsulate cells often elicit foreign body responses, leading to cellular overgrowth and deposition of fibrotic tissue, which in turn diminishes mass transfer to and from transplanted cells. Meanwhile, the encapsulation device must be safe, scalable, and ideally retrievable to meet clinical requirements. Here, a durable and safe nanofibrous device coated with a thin and uniform, fibrosis-mitigating, zwitterionically modified alginate hydrogel for encapsulation of islets and stem cell-derived beta (SC-β) cells is reported...

Radiation therapy (RT), including external beam radiotherapy (EBRT) and internal radioisotope therapy (RIT), has been an indispensable strategy for cancer therapy in clinical practice in recent years. Ionized atoms and free radicals emitted from the nucleus of radioisotopes can cleave a single strand of DNA, inducing the apoptosis of cancer cells. Thus far, nuclides used for RIT could be classified into three main types containing alpha (α), beta (β), and Auger particle emitters. In order to enhance the bioavailability and reduce the physiological toxicity of radioisotopes, various biomaterials have been utilized as multifunctional nanocarriers, including targeting molecules, macromolecular monoclonal antibodies, peptides, inorganic nanomaterials, and organic and polymeric nanomaterials...

Type 1 diabetes mellitus (T1DM) is an autoimmune disease caused by autoreactive T cells targeting the insulin-producing beta (β) cells. Despite advances in insulin therapy, T1DM still leads to high morbidity and mortality in patients. A key focus of T1DM research has been to identify strategies that re-establish self-tolerance and suppress ongoing autoimmunity. Here, we describe a strategy that utilizes pretargeting and glycochemistry to bioengineer β cells in situ to induce β-cell-specific tolerance. We hypothesized that β-cell-targeted Ac4 ManNAz-encapsulated nanoparticles deliver and establish β cells with high levels of surface reactive azide groups...

Alzheimer's disease (AD) treatment is constrained due to the inability of peripherally administered therapeutic molecules to cross the blood-brain barrier. Encapsulated cell biodelivery (ECB) devices, a tissue-targeted approach for local drug release, was previously optimized for human mature nerve growth factor (hmNGF) delivery in AD patients but was found to have reduced hmNGF release over time. To understand the reason behind reduced ECB efficacy, we exposed hmNGF-releasing cells (NGC0211) in vitro to human cerebrospinal fluid (CSF) obtained from Subjective Cognitive Impairment (SCI), Lewy Body Dementia (LBD), and AD patients...

This work aimed to study the antidiabetic effect of encapsulated fucoxanthin with porous starch (PS) in streptozotocin and nicotinamide-induced type 2 diabetic mice. Fucoxanthin was extracted and purified from Sargassum angustifolium and encapsulated in porous starch (PS). Diabetic mice groups were gavaged daily with fucoxanthin (400 mg/kg), either free or encapsulated into PS, and metformin (50 mg/kg) for three weeks. The results exhibited that the fucoxanthin and fucoxanthin-loaded PS markedly prevented the weight gain in treated groups ( p  < ...

Type 1 diabetic patients with severe hypoglycemia unawareness have benefitted from cellular therapies, such as pancreas or islet transplantation; however, donor shortage and the need for immunosuppression limits widespread clinical application. We previously developed an intravascular bioartificial pancreas (iBAP) using silicon nanopore membranes (SNM) for immunoprotection. To ensure ample nutrient delivery, the iBAP will need a cell scaffold with high hydraulic permeability to provide mechanical support and maintain islet viability and function...