Pancreatic islets seeded in a novel bioscaffold forms an organoid to rescue insulin production and reverse hyperglycemia in models of type 1 diabetes
Open accessAbstract
Therapeutic approaches to combat type 1 diabetes (T1D) include donor pancreas transplantation, exogenous insulin administration and immunosuppressive therapies. However, these clinical applications are limited due to insufficient tissue compatible donors, side effects of exogenous insulin administration and/or increased onset of opportunistic infections attributable to induced global immunosuppression. An alternative approach to alleviate disease states is to utilize insulin-producing pancreatic islets seeded in a bioscaffold for implantation into diabetic recipients. The present studies now report that a newly developed cationic polymer biomaterial serves as an efficient bioscaffold for delivery of donor syngeneic pancreatic islet cells to reverse hyperglycemia in murine streptozotocin induced- or non-obese diabetic mouse models of T1D. Intraperitoneal implantation of pancreatic islets seeded within the copolymer bioscaffold supports long-term cell viability, response to extracellular signaling cues and ability to produce soluble factors into the microenvironment. Elevated insulin levels were measured in recipient diabetic mice upon implantation of the islet-seeded biomaterial coupled with reduced blood glucose levels, collectively resulting in increased survival and stabilization of metabolic indices. Importantly, the implanted islet-seeded biomaterial assembled into a solid organoid substructure that reorganized the extracellular matrix compartment and recruited endothelial progenitors for neovascularization. This allowed survival of the graft long-term in vivo and access to the blood for monitoring glucose levels. These results highlight the novelty, simplicity and effectiveness of this biomaterial for tissue regeneration and in vivo restoration of organ functions.
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Human pancreas organoids can be generated from ALDHhigh stem cells and have the potential to produce insulin, but in vivo evidence for engraftment is not yet available.
“Human pancreas organoids can be generated from ALDHhigh stem cells and have the potential to produce insulin146 without in vivo evidence yet to confirm engraftment.”
From Organoids (2022) · cites this paper as [146]
The Discussion (page unavailable) reports insulin production by pancreatic islets seeded in a biomaterial, supporting the general point that the organoid-like construct can produce insulin. The Methods identify the islets as mouse-derived, not human ALDHhigh stem cells. The Abstract also reports long-term graft survival in vivo, though that finding does not establish engraftment of the human stem-cell organoids described in the claim. (LLM, conf=0.85)
Experimental — accuracy not yet measuredOrganoids of murine intestines, livers, and pancreas were successfully transplanted into mice, and the transplanted organoids could restore organ dysfunction.
“Organoids of murine intestines31, livers35,125,126 and pancreas69,146 were successfully transplanted into mice, and the transplanted organoids could restore organ dysfunction.”
From Organoids (2022) · cites this paper as [146]
For the pancreatic portion of the sentence, the Introduction reports that donor mouse islets seeded in a bioscaffold were implanted into diabetic mice, and the Results report restored insulin levels and reduced hyperglycemia. The qualification is that the pancreas-like organoid assembled after implantation; the paper does not report transplanting a preformed organoid. The intestine and liver examples have separate citations and are not assessed here. (LLM, conf=0.86)
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- Authors
- Elizondo, D. M., Brandy, N. Z. D., da Silva, R. L. L., de Moura, T. R., Ali, J., Yang, D., & Lipscomb, M. W.
- Affiliations
- Howard University (US)
- Florida A&M University - Florida State University College of Engineering (US)
- Corresponding author
- Lipscomb, Michael W.
- Venue
- Scientific Reports
- Published
- 2020-03-09
- Volume
- 10
- Issue
- 1
- Pages
- 4362-4362
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC7062832
- OpenAlex
- W3010313464
- Cited by
- 16
- References
- 41
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 4
- FWCI
- 2.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (1428768)
- U.S. Department of Defense (W911NF1410123)
- National Institutes of Health
- National Institute of General Medical Sciences (SC1GM127207)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- type 1 diabetes, pancreatic islets, islet transplantation, bioscaffolds, insulin production, hyperglycemia reversal, streptozotocin-induced diabetes, NOD mice, neovascularization, endothelial progenitor cells, extracellular matrix, graft survival, tissue regeneration
- MeSH terms
- Animals, Blood Glucose, Cell Survival, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 1, Graft Survival, Hyperglycemia, Insulin, Islets of Langerhans, Organoids, Islets of Langerhans Transplantation, Tissue Culture Techniques, Mice, Tissue Scaffolds
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