Encapsulation Of Therapeutic Cells Research Articles

Transplantable cell-encapsulation device using a semipermeable ethylene-vinyl alcohol copolymer membrane in a mouse diabetic model

Cell-based therapy is an attractive approach, and encapsulation of therapeutic cells is a promising strategy because it prevents immune responses and allows transplanted cells to be retrieved in case of dysfunction. Bioartificial pancreas, in which insulin-secreting cells are encapsulated in a semipermeable membrane bag, is a new class of medical device for treating type-I diabetes. In this study, we developed a macroencapsulation device in which the pancreatic beta cell line MIN6 was encapsulated in a semipermeable bag made of an ethylene-vinyl alcohol copolymer membrane. Invitro evaluation of ATP and insulin levels revealed that MIN6 cells grown in Matrigelwithin the device secreted insulin in response to glucose levels. Transplantation of the device lowered blood glucose levels for 30 days in diabetic mice. Histological observation revealed that MIN6 cells formed spheroids in Matrigel, and no host cells were detected within the device. Blood levels of inflammatory cytokines in the transplanted mice were similar to those in non-transplanted mice, and antibody levels in the device were lower than those in the intraperitoneal fluid. These results suggest that the semipermeable ethylene-vinyl alcohol copolymer membrane developed in this study is useful for cell encapsulation in cell-based therapies, including beta-cell macroencapsulation for type-1 diabetes.

Bio-instructive hydrogel expands the paracrine potency of mesenchymal stem cells

The therapeutic efficacy of clinically applied mesenchymal stromal cells (MSCs) is limited due to their injection into harsh in vivo environments, resulting in the significant loss of their secretory function upon transplantation. A potential strategy for preserving their full therapeutic potential is encapsulation of MSCs in a specialized protective microenvironment, for example hydrogels. However, commonly used injectable hydrogels for cell delivery fail to provide the bio-instructive cues needed to sustain and stimulate cellular therapeutic functions. Here we introduce a customizable collagen I-hyaluronic acid (COL-HA)-based hydrogel platform for the encapsulation of MSCs. Cells encapsulated within COL-HA showed a significant expansion of their secretory profile compared to MSCs cultured in standard (2D) cell culture dishes or encapsulated in other hydrogels. Functionalization of the COL-HA backbone with thiol-modified glycoproteins such as laminin led to further changes in the paracrine profile of MSCs. In depth profiling of more than 250 proteins revealed an expanded secretion profile of proangiogenic, neuroprotective and immunomodulatory paracrine factors in COL-HA-encapsulated MSCs with a predicted augmented pro-angiogenic potential. This was confirmed by increased capillary network formation of endothelial cells stimulated by conditioned media from COL-HA-encapsulated MSCs. Our findings suggest that encapsulation of therapeutic cells in a protective COL-HA hydrogel layer provides the necessary bio-instructive cues to maintain and direct their therapeutic potential. Our customizable hydrogel combines bioactivity and clinically applicable properties such as injectability, on-demand polymerization and tissue-specific elasticity, all features that will support and improve the ability to successfully deliver functional MSCs into patients.

Surface‐Triggered In Situ Gelation for Tunable Conformal Hydrogel Coating of Therapeutic Cells and Biomedical Devices

AbstractHydrogel coatings have been proposed as a promising strategy to improve the biocompatibility of therapeutic cells and biomedical devices. However, developed coating methods are only applicable for simple geometries, typical sizes, and limited substrates. In addition, its applications in therapeutic cell encapsulation are hampered by inadequate construction of the hydrogel capsules such as off‐center encapsulation, immense volume, and lack of control over the thickness of capsules. Here, a method called surface‐triggered in situ gelation (STIG) for universal hydrogel coating of multiscale objects ranging from single cells to mini‐organs to biomedical devices with arbitrary shapes and heterogeneous components is reported. By covering cells or devices with calcium carbonate particles, progressive propagation of alginate hydrogel from their surface under the stimulation of GDL is achieved. The thickness of the hydrogel layers can be easily controlled from several micrometers to hundreds of micrometers by adjusting the gelation time and the release rate of calcium ions. Importantly, STIG facilitates accurate, complete, and individual cell encapsulation, which potentially overcomes the pitfalls of conventional strategies. It is further proven that the low‐cost and facile method can potentially lead to advances in different fields by rendering precisely controlled microscale alginate layers on a wide variety of biomedical substrates.