Oxygenation and function of endocrine bioartificial pancreatic tissue constructs under flow for preclinical optimization
Islet transplantation and more recently stem cell-derived islets were shown to successfully re-establish glycemic control in people with type 1 diabetes under immunosuppression. These results were achieved through intraportal infusion which leads to early graft losses and limits the capacity to cont...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2025-01-01
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| Series: | Journal of Tissue Engineering |
| Online Access: | https://doi.org/10.1177/20417314241284826 |
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| author | Brenden N Moeun Florent Lemaire Alexandra M Smink Hamid Ebrahimi Orimi Richard L Leask Paul de Vos Corinne A Hoesli |
| author_facet | Brenden N Moeun Florent Lemaire Alexandra M Smink Hamid Ebrahimi Orimi Richard L Leask Paul de Vos Corinne A Hoesli |
| author_sort | Brenden N Moeun |
| collection | DOAJ |
| description | Islet transplantation and more recently stem cell-derived islets were shown to successfully re-establish glycemic control in people with type 1 diabetes under immunosuppression. These results were achieved through intraportal infusion which leads to early graft losses and limits the capacity to contain and retrieve implanted cells in case of adverse events. Extra-hepatic sites and encapsulation devices have been developed to address these challenges and potentially create an immunoprotective or immune-privileged environment. Many strategies have achieved reversal of hyperglycemia in diabetic rodents. So far, the results have been less promising when transitioning to humans and larger animal models due to challenges in oxygenation and insulin delivery. We propose a versatile in vitro perfusion system to culture and experimentally study the function of centimeter-scale tissues and devices for insulin-secreting cell delivery. The system accommodates various tissue geometries, experimental readouts, and oxygenation tensions reflective of potential transplantation sites. We highlight the system’s applications by using case studies to explore three prominent bioartificial endocrine pancreas (BAP) configurations: (I) with internal flow, (II) with internal flow and microvascularized, and (III) without internal flow. Oxygen concentration profiles modeled computationally were analogous to viability gradients observed experimentally through live/dead endpoint measurements and in case I, time-lapse fluorescence imaging was used to monitor the viability of GFP-expressing cells in real time. Intervascular BAPs were cultured under flow for up to 3 days and BAPs without internal flow for up to 7 days, showing glucose-responsive insulin secretion quantified through at-line non-disruptive sampling. This system can complement other preclinical platforms to de-risk and optimize BAPs and other artificial tissue designs prior to clinical studies. |
| format | Article |
| id | doaj-art-fb5ed01f3a3e4a4d92fc45c0827562df |
| institution | Kabale University |
| issn | 2041-7314 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Journal of Tissue Engineering |
| spelling | doaj-art-fb5ed01f3a3e4a4d92fc45c0827562df2025-01-23T15:03:45ZengSAGE PublishingJournal of Tissue Engineering2041-73142025-01-011610.1177/20417314241284826Oxygenation and function of endocrine bioartificial pancreatic tissue constructs under flow for preclinical optimizationBrenden N Moeun0Florent Lemaire1Alexandra M Smink2Hamid Ebrahimi Orimi3Richard L Leask4Paul de Vos5Corinne A Hoesli6Department of Chemical Engineering, McGill University, Montreal, QC, CanadaDepartment of Chemical Engineering, McGill University, Montreal, QC, CanadaDepartment of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartment of Chemical Engineering, McGill University, Montreal, QC, CanadaDepartment of Biological and Biomedical Engineering, McGill University, Montreal, QC, CanadaDepartment of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsDepartment of Biological and Biomedical Engineering, McGill University, Montreal, QC, CanadaIslet transplantation and more recently stem cell-derived islets were shown to successfully re-establish glycemic control in people with type 1 diabetes under immunosuppression. These results were achieved through intraportal infusion which leads to early graft losses and limits the capacity to contain and retrieve implanted cells in case of adverse events. Extra-hepatic sites and encapsulation devices have been developed to address these challenges and potentially create an immunoprotective or immune-privileged environment. Many strategies have achieved reversal of hyperglycemia in diabetic rodents. So far, the results have been less promising when transitioning to humans and larger animal models due to challenges in oxygenation and insulin delivery. We propose a versatile in vitro perfusion system to culture and experimentally study the function of centimeter-scale tissues and devices for insulin-secreting cell delivery. The system accommodates various tissue geometries, experimental readouts, and oxygenation tensions reflective of potential transplantation sites. We highlight the system’s applications by using case studies to explore three prominent bioartificial endocrine pancreas (BAP) configurations: (I) with internal flow, (II) with internal flow and microvascularized, and (III) without internal flow. Oxygen concentration profiles modeled computationally were analogous to viability gradients observed experimentally through live/dead endpoint measurements and in case I, time-lapse fluorescence imaging was used to monitor the viability of GFP-expressing cells in real time. Intervascular BAPs were cultured under flow for up to 3 days and BAPs without internal flow for up to 7 days, showing glucose-responsive insulin secretion quantified through at-line non-disruptive sampling. This system can complement other preclinical platforms to de-risk and optimize BAPs and other artificial tissue designs prior to clinical studies.https://doi.org/10.1177/20417314241284826 |
| spellingShingle | Brenden N Moeun Florent Lemaire Alexandra M Smink Hamid Ebrahimi Orimi Richard L Leask Paul de Vos Corinne A Hoesli Oxygenation and function of endocrine bioartificial pancreatic tissue constructs under flow for preclinical optimization Journal of Tissue Engineering |
| title | Oxygenation and function of endocrine bioartificial pancreatic tissue constructs under flow for preclinical optimization |
| title_full | Oxygenation and function of endocrine bioartificial pancreatic tissue constructs under flow for preclinical optimization |
| title_fullStr | Oxygenation and function of endocrine bioartificial pancreatic tissue constructs under flow for preclinical optimization |
| title_full_unstemmed | Oxygenation and function of endocrine bioartificial pancreatic tissue constructs under flow for preclinical optimization |
| title_short | Oxygenation and function of endocrine bioartificial pancreatic tissue constructs under flow for preclinical optimization |
| title_sort | oxygenation and function of endocrine bioartificial pancreatic tissue constructs under flow for preclinical optimization |
| url | https://doi.org/10.1177/20417314241284826 |
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