Transplantation of Encapsulated Pancreatic Islets as a Treatment for Patients with Type 1 Diabetes Mellitus

Qi, Meirigeng

doi:10.1155/2014/429710

Cited by 56 publications

(37 citation statements)

References 140 publications

(135 reference statements)

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“…Innate immune reaction occurs immediately after exposure and is typically initiated by cellular mediators such as macrophages, neutrophils, and natural killer cells [37]. To further study if the PEG hydrogel alone (no islets) was attracting some of the host immune cells, frozen hydrogel sections were immunostained with Alexa fluor 647 anti-mouse F4/80 antibody for murine macrophages (red) and DAPI (blue) for nuclear staining.…”

Section: Resultsmentioning

confidence: 99%

Injectable polyethylene glycol hydrogel for islet encapsulation: an in vitro and in vivo characterization

Knobeloch

Abadi

Bruns

et al. 2017

Biomed. Phys. Eng. Express

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An injection of hydrogel-encapsulated islets that controls blood glucose levels over long term would provide a much needed alternative treatment for type 1 diabetes mellitus (T1DM). To this end, we tested the feasibility of using an injectable polyethylene glycol (PEG) hydrogel as a scaffold for islet encapsulation. Encapsulated islets cultured in vitro for 6 days showed excellent cell viability and released insulin with higher basal and stimulated insulin secretion than control islets. Host responses to PEG hydrogels were studied by injecting PEG hydrogels (no treatment and vehicle controls used) into the peritoneal cavities of B6D2F1 mice and monitoring alterations in body weight, food and water intake, and blood glucose levels. After 2 weeks, peritoneal cavity cells were harvested, followed by hydrogel retrieval, and extraction of spleens. Body weights, food and water intake, and blood glucose levels were unaltered in mice injected with hydrogels compared to no treatment and vehicle-injected control mice. Frozen sections of a hydrogel showed the presence of tissues and small number of immune cells surrounding the hydrogel but no cell infiltration into the hydrogel bulk. Spleen sizes were not significantly different under the experimental conditions. Peritoneal cavity cells were slightly higher in mice injected with hydrogels compared to control mice but no statistical difference between vehicle- and hydrogel-injected mice was noted. As an in vivo feasibility study, streptozotocin-induced diabetic mice were injected with vehicle or hydrogels containing 50 islets each into two sites, the peritoneal cavity and a subcutaneous site on the back. Transient control of blood glucose levels were observed in mice injected with hydrogels containing islets. In summary, we developed an injectable PEG hydrogel that supported islet function and survival in vitro and in vivo and elicited only a mild host response. Our work illustrates the feasibility of using injectable PEG hydrogels for islet encapsulation.

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Section: Resultsmentioning

confidence: 99%

Injectable polyethylene glycol hydrogel for islet encapsulation: an in vitro and in vivo characterization

Knobeloch

Abadi

Bruns

et al. 2017

Biomed. Phys. Eng. Express

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“…Alginate hydrogels have been widely used for in vitro follicle culture (Brito et al, 2014; Camboni et al, 2013; Hornick et al, 2012; Kniazeva et al, 2015; Kreeger et al, 2006; Laronda et al, 2014; West et al, 2007; Xiao et al, 2015a; Xiao et al, 2015b; Xu et al, 2009), as well as for cell transplantation, such as islets as a therapy for type 1 diabetes (Köllmer et al, 2015; Ludwig et al, 2013; Qi, 2014; Scharp and Marchetti, 2013) and also ovarian follicles (David et al, 2017; Vanacker et al, 2014). Islets are encapsulated within the hydrogel for isolation from the host over several months, yet the islets are able to survive, sense blood glucose levels, and secrete insulin that can distribute systemically to normalize blood glucose levels.…”

Section: Discussionmentioning

confidence: 99%

Retrievable hydrogels for ovarian follicle transplantation and oocyte collection

Rios

Kniazeva

Lee

et al. 2018

Biotech & Bioengineering

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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. However, follicle atresia after transplantation and risk of reintroducing malignant cells have prevented this procedure from becoming widely adopted in clinics. Herein, we investigated the encapsulation of ovarian follicles in alginate hydrogels that isolate the graft from the host, yet allows for maturation after transplantation at a heterotopic (i.e., subcutaneous) site, a process we termed in vivo follicle maturation. Survival of multiple follicle populations was confirmed via histology, with the notable development of the antral follicles. Collected oocytes (63%) exhibited polar body extrusion and were fertilized by intracytoplasmic sperm injection and standard in vitro fertilization procedures. Successfully fertilized oocytes developed to the pronucleus (14%), two-cell (36%), and four-cell (7%) stages. Furthermore, ovarian follicles cotransplanted with metastatic breast cancer cells within the hydrogels allowed for retrieval of the follicles, and no mice developed tumors after removal of the implant, confirming that the hydrogel prevented seeding of disease within the host. Collectively, these findings demonstrate a viable option for safe use of potentially cancer-laden ovarian donor tissue for in vivo follicle maturation within a retrievable hydrogel and subsequent oocyte collection. Ultimately, this technology may provide novel options to preserve fertility for young female patients with cancer.

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“…Devices, such as Theracyte, have been implanted to promote vascularization of the device, with islets loaded through a port at later times (Kumagai‐Braesch et al, ; Qi, ). Similarly, the Sernova pouch is pre‐vascularized prior to delivery of islets through channels that are opened in the device (Qi, ). Herein, we demonstrated that PDMS casting can be employed to create devices with regularly spaced channels.…”

Section: Discussionmentioning

confidence: 99%

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

Rios

Zhang

Luo

et al. 2016

Biotech & Bioengineering

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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. PEG solutions are mixed with islets, which are then cast into PDMS molds for subsequent crosslinking. The molds can also be employed to provide complex architectures, such as microchannels that may allow vascular ingrowth through pre-defined regions of the hydrogel. PDMS molds allowed for the formation of stable gels with encapsulation of islets, and in complex architectures. Hydrogel devices with a thickness of 600 μm containing 500 islets promoted normoglycemia within 12 days following transplantation into the epididymal fat pad, which was sustained over the two-month period of study until removal of the device. The inclusion of microchannels, which had a similar minimum distance between islets and the hydrogel surface, similarly promoted normoglycemia. A glucose challenge test indicated hydrogel devices achieved normoglycemia 90 min post-dextrose injections, similar to control mice with native pancreata. Histochemical staining revealed that transplanted islets, identified as insulin positive, were viable and isolated from host tissue at 8 weeks post-transplantation, yet devices with microchannels had tissue and vascular ingrowth within the channels. Taken together, these results demonstrate a system for creating non-degradable hydrogels with complex geometries for encapsulating islets capable of restoring normoglycemia, which may expand islet transplantation as a treatment option for diabetic patients. Biotechnol. Bioeng. 2016;113: 2485-2495. © 2016 Wiley Periodicals, Inc.

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Transplantation of Encapsulated Pancreatic Islets as a Treatment for Patients with Type 1 Diabetes Mellitus

Cited by 56 publications

References 140 publications

Injectable polyethylene glycol hydrogel for islet encapsulation: an in vitro and in vivo characterization

Injectable polyethylene glycol hydrogel for islet encapsulation: an in vitro and in vivo characterization

Retrievable hydrogels for ovarian follicle transplantation and oocyte collection

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

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