Cell Therapy for T1D Beyond BLA: Gearing Up Toward Clinical Practice.

Type 1 diabetes (T1D) remains a significant global health challenge and patients with T1D need lifelong insulin therapy. Islet transplantation holds transformative potential by replacing autoimmune-mediated destruction of insulin-producing beta cells. This review examines the trajectory of islet transplantation for T1D, focusing on the process and benefits of obtaining biologics license application (BLA) approval for cell-based therapies.

IL-12-producing cytokine factories induce precursor exhausted T cells and elimination of primary and metastatic tumors.

Background: Curative responses to immunotherapy require the generation of robust systemic immunity with limited toxicity. Recruitment of T cell populations such as precursor exhausted T cells (Tpex) from lymphoid tissues to tumors is a hallmark of effective treatment. However, the ability to efficiently induce this recruitment is lacking in current immunotherapy approaches.

Postmodification with Polycations Enhances Key Properties of Alginate-Based Multicomponent Microcapsules.

Postmodification of alginate-based microspheres with polyelectrolytes (PEs) is commonly used in the cell encapsulation field to control microsphere stability and permeability. However, little is known about how different applied PEs shape the microsphere morphology and properties, particularly . Here, we addressed this question using model multicomponent alginate-based microcapsules postmodified with PEs of different charge and structure.

Phase-changing citrate macromolecule combats oxidative pancreatic islet damage, enables islet engraftment and function in the omentum.

Clinical outcomes for total-pancreatectomy followed by intraportal islet autotransplantation (TP-IAT) to treat chronic pancreatitis (CP) are suboptimal due to pancreas inflammation, oxidative stress during islet isolation, and harsh engraftment conditions in the liver's vasculature. We describe a thermoresponsive, antioxidant macromolecule poly(polyethylene glycol citrate---isopropylacrylamide) (PPCN) to protect islet redox status and function and to enable extrahepatic omentum islet engraftment. PPCN solution transitions from a liquid to a hydrogel at body temperature.

Screening hydrogels for antifibrotic properties by implanting cellularly barcoded alginates in mice and a non-human primate.

Screening implantable biomaterials for antifibrotic properties is constrained by the need for in vivo testing. Here we show that the throughput of in vivo screening can be increased by cellularly barcoding a chemically modified combinatorial library of hydrogel formulations. The method involves the implantation of a mixture of alginate formulations, each barcoded with human umbilical vein endothelial cells from different donors, and the association of the identity and performance of each formulation by genotyping single nucleotide polymorphisms of the cells via next-generation sequencing.

Heterogeneous toroidal spiral particles for islet encapsulation.

Transplantable cell encapsulation systems present a promising approach to deliver a therapeutic solution from hormone-producing cells for the treatment of endocrine diseases like type 1 diabetes. However, the development of a broadly effective and safe transplantation system has been challenging. While some current micro-sized capsules have been optimized for adequate nutrient and metabolic transport, they lack the robustness and retrievability for the clinical safety translation that macro-devices may offer.

Evaluation of encapsulating and microporous nondegradable hydrogel scaffold designs on islet engraftment in rodent models of diabetes.

Islet transplantation is a promising therapeutic option for type 1 diabetes mellitus, yet the current delivery into the hepatic portal vasculature is limited by poor engraftment. Biomaterials have been used as a means to promote engraftment and function at extrahepatic sites, with strategies being categorized as encapsulation or microporous scaffolds that can either isolate or integrate islets with the host tissue, respectively. Although these approaches are typically studied separately using distinct material platforms, herein, we developed nondegradable polyethylene glycol (PEG)-based hydrogels for islet encapsulation or as microporous scaffolds for islet seeding to compare the initial engraftment and function of islets in syngeneic diabetic mice.

Retrievable hydrogels for ovarian follicle transplantation and oocyte collection.

Cancer survivorship rates have drastically increased due to improved efficacy of oncologic treatments. Consequently, clinical concerns have shifted from solely focusing on survival to quality of life, with fertility preservation as an important consideration. Among fertility preservation strategies for female patients, ovarian tissue cryopreservation and subsequent reimplantation has been the only clinical option available to cancer survivors with cryopreserved tissue.

Dynamic transcription factor activity networks in response to independently altered mechanical and adhesive microenvironmental cues.

Multiple aspects of the local extracellular environment profoundly affect cell phenotype and function. Physical and chemical cues in the environment trigger intracellular signaling cascades that ultimately activate transcription factors (TFs) - powerful regulators of the cell phenotype. TRACER (TRanscriptional Activity CEll aRrays) was employed for large-scale, dynamic quantification of TF activity in human fibroblasts cultured on hydrogels with a controlled elastic modulus and integrin ligand density.

Mold-casted non-degradable, islet macro-encapsulating hydrogel devices for restoration of normoglycemia in diabetic mice.

Islet transplantation is a potential cure for diabetic patients, however this procedure is not widely adopted due to the high rate of graft failure. Islet encapsulation within hydrogels is employed to provide a three-dimensional microenvironment conducive to survival of transplanted islets to extend graft function. Herein, we present a novel macroencapsulation device, composed of PEG hydrogel, that combines encapsulation with lithography techniques to generate polydimethylsiloxane (PDMS) molds.

The enhancement of bone allograft incorporation by the local delivery of the sphingosine 1-phosphate receptor targeted drug FTY720.

Poor vascularization coupled with mechanical instability is the leading cause of post-operative complications and poor functional prognosis of massive bone allografts. To address this limitation, we designed a novel continuous polymer coating system to provide sustained localized delivery of pharmacological agent, FTY720, a selective agonist for sphingosine 1-phosphate receptors, within massive tibial defects. In vitro drug release studies validated 64% loading efficiency with complete release of compound following 14 days.