Emerging strategies for beta cell transplantation to treat diabetes

Paez‐Mayorga, Jesus; Lukin, Izeia; Emerich, Dwaine F.; Vos, Paul De; Orive, Gorka; Grattoni, Alessandro

doi:10.1016/j.tips.2021.11.007

Cited by 21 publications

(12 citation statements)

References 71 publications

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“…However, we must acknowledge that in the current design, immune-isolating function is weak due to the semiopen feature of HATS. However, such a structure may be favorable in vascularization of the device with the direct supply of oxygen and nutrients, which is now understood to be necessary for long-term engraftment. , Besides, a hot issue in cell therapy recently has been the local immunosuppression, and HATS combining with such technology may produce a translatable approach for cell encapsulation. − In summary, HATS represents the new generation of encapsulation platforms integrating control over both cell arrangement and mass transfer into a two-dimensional membrane system combining plastic with hydrogel. We believe that our approach could pave the way for the improved management of endocrine disorders.…”

Section: Discussionmentioning

confidence: 99%

Hydrogel-Bondable Asymmetric Planar Membranes with Hierarchical Pore Structures for Cell Scaffolding and Encapsulation

Wang

Luo

et al. 2023

ACS Biomater. Sci. Eng.

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Biomaterials for cell replacement therapy could facilitate the delivery, function, and retrieval of transplanted therapeutic cells. However, the limited capacity to accommodate a sufficient quantity of cells in biomedical devices has hindered the success of clinical application, resulting from the suboptimal spatial organization of cells and insufficient permeation of nutrients in the materials. Herein, through the immersion-precipitation phase transfer (IPPT) process from polyether sulfone (PES), we develop planar asymmetric membranes with a hierarchical pore architecture spanning from nanopores (∼20 nm) in the dense skin and open-ended microchannel arrays with gradient pore size increasing vertically from microns to ∼100 μm. The nanoporous skin would be an ultrathin diffusion barrier, while the microchannels could support high-density cell loading by acting as separate chambers allowing uniform distribution of cells in the scaffold. Alginate hydrogel could permeate into the channels and form a sealing layer after gelation, which could slow down the invasion of host immune cells into the scaffold. The hybrid thin-sheet encapsulation system (∼400 μm thick) could protect allogeneic cells over half-year after intraperitoneal (IP) implantation in immune-competent mice. Such structural membranes and plastic–hydrogel hybrids of thin dimensions could find important applications in cell delivery therapy.

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Section: Discussionmentioning

confidence: 99%

Hydrogel-Bondable Asymmetric Planar Membranes with Hierarchical Pore Structures for Cell Scaffolding and Encapsulation

Wang

Luo

et al. 2023

ACS Biomater. Sci. Eng.

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“…2). The FBR to materials implanted subQ has been harnessed to create pre-vascularized sites for islet transplantation 4,33 . We posit that, in a similar fashion, NICHE biointegration harnessed the FBR to drive vascularization into the cell reservoir, which was further potentiated by the tissue remodeling properties of MSCs 19,34 .…”

Section: Discussionmentioning

confidence: 99%

“…Pancreatic islet encapsulation promises to overcome the need for toxic systemic immunosuppression regimens 4 . Most encapsulation strategies rely on physical immunoisolation; where islets are enveloped in semipermeable materials that permit oxygen, nutrient, and metabolite exchange, yet limit immune cell infiltration 5,6 .…”

mentioning

confidence: 99%

Implantable niche with local immunosuppression for islet allotransplantation achieves type 1 diabetes reversal in rats

et al. 2022

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Pancreatic islet transplantation efficacy for type 1 diabetes (T1D) management is limited by hypoxia-related graft attrition and need for systemic immunosuppression. To overcome these challenges, we developed the Neovascularized Implantable Cell Homing and Encapsulation (NICHE) device, which integrates direct vascularization for facile mass transfer and localized immunosuppressant delivery for islet rejection prophylaxis. Here, we investigated NICHE efficacy for allogeneic islet transplantation and long-term diabetes reversal in an immunocompetent, male rat model. We demonstrated that allogeneic islets transplanted within pre-vascularized NICHE were engrafted, revascularized, and functional, reverting diabetes in rats for over 150 days. Notably, we confirmed that localized immunosuppression prevented islet rejection without inducing toxicity or systemic immunosuppression. Moreover, for translatability efforts, we showed NICHE biocompatibility and feasibility of deployment as well as short-term allogeneic islet engraftment in an MHC-mismatched nonhuman primate model. In sum, the NICHE holds promise as a viable approach for safe and effective islet transplantation and long-term T1D management.

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“…Finally, two other products, MailPan ® and Seraxis, use insulin-producing cells of different origins embedded in an immune-protective membrane. In conclusion, several efforts have been made to find an alternative source of islets, as indicated by numerous developed products and ongoing clinical trials ( 224 , 225 ).…”

Section: Insulin-producing Cells: Finding An Alternative Source To Do...mentioning

confidence: 99%

Bioengineering the Vascularized Endocrine Pancreas: A Fine-Tuned Interplay Between Vascularization, Extracellular-Matrix-Based Scaffold Architecture, and Insulin-Producing Cells

Pignatelli¹,

Campo

Neroni

et al. 2022

Transpl Int

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Intrahepatic islet transplantation is a promising β-cell replacement strategy for the treatment of type 1 diabetes. Instant blood-mediated inflammatory reactions, acute inflammatory storm, and graft revascularization delay limit islet engraftment in the peri-transplant phase, hampering the success rate of the procedure. Growing evidence has demonstrated that islet engraftment efficiency may take advantage of several bioengineering approaches aimed to recreate both vascular and endocrine compartments either ex vivo or in vivo. To this end, endocrine pancreas bioengineering is an emerging field in β-cell replacement, which might provide endocrine cells with all the building blocks (vascularization, ECM composition, or micro/macro-architecture) useful for their successful engraftment and function in vivo. Studies on reshaping either the endocrine cellular composition or the islet microenvironment have been largely performed, focusing on a single building block element, without, however, grasping that their synergistic effect is indispensable for correct endocrine function. Herein, the review focuses on the minimum building blocks that an ideal vascularized endocrine scaffold should have to resemble the endocrine niche architecture, composition, and function to foster functional connections between the vascular and endocrine compartments. Additionally, this review highlights the possibility of designing bioengineered scaffolds integrating alternative endocrine sources to overcome donor organ shortages and the possibility of combining novel immune-preserving strategies for long-term graft function.

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Emerging strategies for beta cell transplantation to treat diabetes

Cited by 21 publications

References 71 publications

Hydrogel-Bondable Asymmetric Planar Membranes with Hierarchical Pore Structures for Cell Scaffolding and Encapsulation

Hydrogel-Bondable Asymmetric Planar Membranes with Hierarchical Pore Structures for Cell Scaffolding and Encapsulation

Implantable niche with local immunosuppression for islet allotransplantation achieves type 1 diabetes reversal in rats

Bioengineering the Vascularized Endocrine Pancreas: A Fine-Tuned Interplay Between Vascularization, Extracellular-Matrix-Based Scaffold Architecture, and Insulin-Producing Cells

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