Islet Encapsulation: A Long-Term Treatment for Type 1 Diabetes

Moeun, Brenden N.; Ling, Si Da; Gasparrini, Marco; Rutman, Alissa K.; Negi, Sarita; Paraskevas, Steven; Hoesli, Corinne A.

doi:10.1016/b978-0-12-801238-3.11135-3

Cited by 8 publications

(14 citation statements)

References 23 publications

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“…The growing list of approved cell therapy products (https://www.fda.gov/vaccines-blood-biologics/cellular-genetherapy-products/approved-cellular-and-gene-therapy-products) not only for people suffering from blood disorders and cancers, but also for cartilage, retinal and other tissue defects portends a new era in the treatment of degenerative disease. Groundbreaking clinical trials are testing the safety and efficacy of embryonic stem cell-derived products transplanted in various encapsulation devices to treat type 1 diabetes (Moeun et al, 2019).…”

Section: Manual Handling Of Cell Therapy Products Using Functionally Open Cell Culture Systemsmentioning

confidence: 99%

The importance and future of biochemical engineering

Whitehead

Banta

Bentley

et al. 2020

Biotech & Bioengineering

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Thematic areas Novel products and non-traditional organismsMuch of our view of biology and what is possible in biotechnology is shaped by what we learn in a small collection of well-characterized model cells like E. coli, S. cerevisiae, and CHO cells. Most educational resources are based on the discoveries made in these systems, and thus our view of life is often viewed in the context of these cells. Therefore, the fields of metabolic engineering and synthetic biology frequently turn to this short list of model cells as "chassis" for technology development. This has led to fantastic accomplishments, with undoubtedly great new advances on the horizon.By contrast, investigation of non-model organisms, development of genetic tools in nonmodel organisms, and development of non-model organisms for use as chassis has been more limited. There are many important reasons why we need to expand applied research activities with non-model cells and organisms (Figure 1).• Alternative cells provide new opportunities for metabolic engineering and synthetic biology. Non-model cells may serve as superior "chassis" organisms as they can thrive in extreme environments and are already evolved for optimized performance of various capabilities. Non-model cells can provide different capabilities like stress-tolerant phenotypes and enhanced catabolic breadth (described in a recent review (Thorwall, Schwartz, Chartron, & Wheeldon, 2020)). Thus, alternative chassis may prove to be more suitable for future applications,, including the use of cell-free systems (Silverman, Karim, & Jewett, 2019).• Non-model organisms are already involved in a wide variety of well-established and scaled bioprocesses like wastewater treatment, metal mining, nitrogen fixation, and food production. Further investigation into the organisms found in existing bioprocesses will lead to new understandings of critical mechanisms, metabolic capacities, microbial competition, and mechanisms for robustness of cell-cell communication networks.

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Section: Manual Handling Of Cell Therapy Products Using Functionally Open Cell Culture Systemsmentioning

confidence: 99%

The importance and future of biochemical engineering

Whitehead

Banta

Bentley

et al. 2020

Biotech & Bioengineering

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“…Transplanted cells need to be protected from the host immunological attack while maintaining sufficient metabolic exchange and secretion of their respective therapeutic agents 3 . The semi‐permeability and high water content of hydrogel facilitate the diffusion‐dependent exchange of nutrients and metabolic wastes between encapsulated cells and their surrounding environment while protecting these therapeutic cells from attack by host antibodies and immune cells 4,5 …”

Section: Introductionmentioning

confidence: 99%

Waffle‐inspired hydrogel‐based macrodevice for spatially controlled distribution of encapsulated therapeutic microtissues and pro‐angiogenic endothelial cells

Pham

Zuo

Chen

et al. 2023

Bioengineering & Transla Med

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Macro‐encapsulation systems for delivery of cellular therapeutics in diabetes treatment offer major advantages such as device retrievability and high cell packing density. However, microtissue aggregation and absence of vasculature have been implicated in the inadequate transfer of nutrients and oxygen to the transplanted cellular grafts. Herein, we develop a hydrogel‐based macrodevice to encapsulate therapeutic microtissues positioned in homogeneous spatial distribution to mitigate their aggregation while concurrently supporting an organized intra‐device network of vascular‐inductive cells. Termed Waffle‐inspired Interlocking Macro‐encapsulation (WIM) device, this platform comprises two modules with complementary topography features that fit together in a lock‐and‐key configuration. The waffle‐inspired grid‐like micropattern of the “lock” component effectively entraps insulin‐secreting microtissues in controlled locations while the interlocking design places them in a co‐planar spatial arrangement with close proximity to vascular‐inductive cells. The WIM device co‐laden with INS‐1E microtissues and human umbilical vascular endothelial cells (HUVECs) maintains desirable cellular viability in vitro with the encapsulated microtissues retaining their glucose‐responsive insulin secretion while embedded HUVECs express pro‐angiogenic markers. Furthermore, a subcutaneously implanted alginate‐coated WIM device encapsulating primary rat islets achieves blood glucose control for 2 weeks in chemically induced diabetic mice. Overall, this macrodevice design lays foundation for a cell delivery platform, which has the potential to facilitate nutrients and oxygen transport to therapeutic grafts and thereby might lead to improved disease management outcome.

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“…Lifelong immunosuppression is also associated with increased risks of infection or cancer (Ryan et al, 2004). As an alternative, numerous micro-or macroencapsulation methods have been proposed to safely deliver the therapeutic cells while protecting them against host immune attack (Scharp and Marchetti, 2014;Moeun et al, 2019). Microencapsulation devices each contain one or a few islets (Scharp and Marchetti, 2014), while macroencapsulation approaches aim to deliver an entire therapeutic cell dose in one or a few devices.…”

Section: Introductionmentioning

confidence: 99%

“…For example, Mridha et al (2020) have developed a prevascularized device for subcutaneous implantation that consists of polycaprolactone scaffolds housing alginate-microencapsulated islets. While this and other designs have shown promising blood glucose normalization results in rodents, effective scale-up for therapeutic use in humans has yet to be demonstrated (Song and Roy, 2016;Desai and Shea, 2017;Moeun et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

An in vitro Perfused Macroencapsulation Device to Study Hemocompatibility and Survival of Islet-Like Cell Clusters

Fernandez

Danielczak

Gauvin-Rossignol

et al. 2021

Front. Bioeng. Biotechnol.

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Transplantation of hydrogel-encapsulated pancreatic islets is a promising long-term treatment for type 1 diabetes that restores blood glucose regulation while providing graft immunoprotection. Most human-scale islet encapsulation devices that rely solely on diffusion fail to provide sufficient surface area to meet islet oxygen demands. Perfused macroencapsulation devices use blood flow to mitigate oxygen limitations but increase the complexity of blood-device interactions. Here we describe a human-scale in vitro perfusion system to study hemocompatibility and performance of islet-like cell clusters (ILCs) in alginate hydrogel. A cylindrical perfusion device was designed for multi-day culture without leakage, contamination, or flow occlusion. Rat blood perfusion was assessed for prothrombin time and international normalized ratio and demonstrated no significant change in clotting time. Ex vivo perfusion performed with rats showed patency of the device for over 100 min using Doppler ultrasound imaging. PET-CT imaging of the device successfully visualized metabolically active mouse insulinoma 6 ILCs. ILCs cultured for 7 days under static conditions exhibited abnormal morphology and increased activated caspase-3 staining when compared with the perfused device. These findings reinforce the need for convective transport in macroencapsulation strategies and offer a robust and versatile in vitro system to better inform preclinical design.

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Islet Encapsulation: A Long-Term Treatment for Type 1 Diabetes

Cited by 8 publications

References 23 publications

The importance and future of biochemical engineering

The importance and future of biochemical engineering

Waffle‐inspired hydrogel‐based macrodevice for spatially controlled distribution of encapsulated therapeutic microtissues and pro‐angiogenic endothelial cells

An in vitro Perfused Macroencapsulation Device to Study Hemocompatibility and Survival of Islet-Like Cell Clusters

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