Curated Papers > Recent high-impact research on "organoids" (IF≥30, last 5 years)

Towards a better understanding of diabetes mellitus using organoid models.

Literature Information

DOI	10.1038/s41574-022-00797-x
PMID	36670309
Journal	Nature reviews. Endocrinology
Impact Factor	40.0
JCR Quartile	Q1
Publication Year	2023
Times Cited	35
Keywords	diabetes mellitus models, organoids, pancreatic physiology
Literature Type	Journal Article, Review
ISSN	1759-5029
Pages	232-248
Issue	19(4)
Authors	Belin Selcen Beydag-Tasöz, Siham Yennek, Anne Grapin-Botton

TL;DR

This research highlights the emerging role of organoid models in studying diabetes mellitus, emphasizing their ability to replicate human pancreatic cell development and the response of target organs to pancreatic hormones. By integrating organoid technology with bioengineering, the study aims to enhance understanding of diabetes as a multi-organ disease and improve existing models for more effective research and therapeutic strategies.

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diabetes mellitus models · organoids · pancreatic physiology

Abstract

Our understanding of diabetes mellitus has benefited from a combination of clinical investigations and work in model organisms and cell lines. Organoid models for a wide range of tissues are emerging as an additional tool enabling the study of diabetes mellitus. The applications for organoid models include studying human pancreatic cell development, pancreatic physiology, the response of target organs to pancreatic hormones and how glucose toxicity can affect tissues such as the blood vessels, retina, kidney and nerves. Organoids can be derived from human tissue cells or pluripotent stem cells and enable the production of human cell assemblies mimicking human organs. Many organ mimics relevant to diabetes mellitus are already available, but only a few relevant studies have been performed. We discuss the models that have been developed for the pancreas, liver, kidney, nerves and vasculature, how they complement other models, and their limitations. In addition, as diabetes mellitus is a multi-organ disease, we highlight how a merger between the organoid and bioengineering fields will provide integrative models.

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Primary Questions Addressed

1. What specific advantages do organoid models offer over traditional cell lines in studying the pathophysiology of diabetes mellitus?
2. How do organoid models derived from pluripotent stem cells compare to those derived from adult human tissues in terms of mimicking pancreatic function?
3. In what ways can organoid models contribute to the understanding of the systemic effects of diabetes on organs such as the retina and kidneys?
4. What are the current limitations of organoid models in diabetes research, and how might future advancements in bioengineering address these challenges?
5. How can integrating organoid technology with other modeling approaches enhance our understanding of multi-organ interactions in diabetes mellitus?

Key Findings

Research Background and Objectives

Diabetes mellitus is a complex metabolic disorder that affects multiple organs. Traditional research has relied on clinical investigations and model organisms, but recent advancements in organoid technology offer new avenues for studying diabetes. The objective of this research is to explore the potential of organoid models derived from human tissues and pluripotent stem cells to investigate pancreatic cell development, organ responses to pancreatic hormones, and the effects of glucose toxicity on various tissues.

Main Methods/Materials/Experimental Design

The study focuses on the development and application of organoid models for different organs related to diabetes. These organoids are created from human tissue cells or pluripotent stem cells, providing a three-dimensional structure that closely mimics human organ function. The following flowchart illustrates the technical approach taken in this research:

Key Results and Findings

• Organoid Availability: Several organoid models relevant to diabetes, including those for the pancreas, liver, kidney, nerves, and vasculature, have been developed.
• Functional Mimicry: These organoids effectively replicate the physiological functions of human organs, allowing for detailed study of organ interactions in the context of diabetes.
• Limited Studies: Despite the availability of organoid models, only a limited number of studies have utilized these models to explore diabetes-related phenomena.

Main Conclusions/Significance/Innovation

The integration of organoid technology with bioengineering presents a significant advancement in diabetes research. This approach allows for:

• Multi-Organ Modeling: The ability to study diabetes as a multi-organ disease, facilitating a better understanding of the disease's systemic effects.
• Enhanced Research Capabilities: Organoids provide a platform for investigating complex interactions between pancreatic hormones and target organs, improving insights into diabetes pathology.
• Future Applications: The merger of organoid and bioengineering fields holds promise for developing more comprehensive models that can lead to innovative therapeutic strategies.

Research Limitations and Future Directions

• Limited Research Utilization: The potential of organoid models has not been fully realized, with many available models remaining underutilized in diabetes research.
• Need for Standardization: There is a need for standardized protocols in organoid development to ensure reproducibility and comparability across studies.
• Future Directions: Future research should focus on expanding the range of organoid models, enhancing their functional fidelity, and integrating them into multi-organ systems to better simulate the complexities of diabetes mellitus.

Aspect	Details
Research Background	Diabetes mellitus affects multiple organs; organoids offer new insights.
Main Methods	Organoids from human tissues/pluripotent stem cells; multi-organ focus.
Key Findings	Several organoid models exist, but limited studies conducted.
Conclusions	Organoids enable multi-organ modeling; potential for novel therapies.
Limitations	Underutilization and need for standardization; future expansion needed.

References

1. Treatment of type 2 diabetes: challenges, hopes, and anticipated successes. - Michael A Nauck;Jakob Wefers;Juris J Meier - The lancet. Diabetes & endocrinology (2021)
2. The hope and the hype of organoid research. - Meritxell Huch;Juergen A Knoblich;Matthias P Lutolf;Alfonso Martinez-Arias - Development (Cambridge, England) (2017)
3. Building consensus on definition and nomenclature of hepatic, pancreatic, and biliary organoids. - Ary Marsee;Floris J M Roos;Monique M A Verstegen; ;Helmuth Gehart;Eelco de Koning;Frédéric Lemaigre;Stuart J Forbes;Weng Chuan Peng;Meritxell Huch;Takanori Takebe;Ludovic Vallier;Hans Clevers;Luc J W van der Laan;Bart Spee - Cell stem cell (2021)
4. Diabetes through a 3D lens: organoid models. - Anastasia Tsakmaki;Patricia Fonseca Pedro;Gavin A Bewick - Diabetologia (2020)
5. Spontaneous reassociation of dispersed adult rat pancreatic islet cells into aggregates with three-dimensional architecture typical of native islets. - P A Halban;S L Powers;K L George;S Bonner-Weir - Diabetes (1987)
6. Controlled aggregation of primary human pancreatic islet cells leads to glucose-responsive pseudoislets comparable to native islets. - Janneke Hilderink;Siebe Spijker;Françoise Carlotti;Lydia Lange;Marten Engelse;Clemens van Blitterswijk;Eelco de Koning;Marcel Karperien;Aart van Apeldoorn - Journal of cellular and molecular medicine (2015)
7. Advances Toward Engineering Functionally Mature Human Pluripotent Stem Cell-Derived β Cells. - Leonardo Velazco-Cruz;Madeleine M Goedegebuure;Jeffrey R Millman - Frontiers in bioengineering and biotechnology (2020)
8. Strategies for durable β cell replacement in type 1 diabetes. - Todd M Brusko;Holger A Russ;Cherie L Stabler - Science (New York, N.Y.) (2021)
9. hPSC-derived organoids: models of human development and disease. - Tristan Frum;Jason R Spence - Journal of molecular medicine (Berlin, Germany) (2021)
10. Understanding the Long-Lasting Effects of Fetal Nutrient Restriction versus Exposure to an Obesogenic Diet on Islet-Cell Mass and Function. - Stephanie E O'Hara;Kelly M Gembus;Lisa M Nicholas - Metabolites (2021)

Literatures Citing This Work

1. Rodent models to study type 1 and type 2 diabetes induced human diabetic nephropathy. - Amit Talukdar;Mandira Basumatary - Molecular biology reports (2023)
2. The role of organoids in cancer research. - Zhen Fang;Peijuan Li;Fengying Du;Liang Shang;Leping Li - Experimental hematology & oncology (2023)
3. Understanding the Role of the Gut Microbiome in Diabetes and Therapeutics Targeting Leaky Gut: A Systematic Review. - Aishwarya Sadagopan;Anas Mahmoud;Maha Begg;Mawada Tarhuni;Monique Fotso;Natalie A Gonzalez;Raghavendra R Sanivarapu;Usama Osman;Abishek Latha Kumar;Lubna Mohammed - Cureus (2023)
4. Targeted Gene Silencing by Using GapmeRs in Differentiating Human-Induced Pluripotent Stem Cells (hiPSC) Toward Pancreatic Progenitors. - Lucas Unger;Luiza Ghila;Simona Chera - Methods in molecular biology (Clifton, N.J.) (2024)
5. Current advancement in the preclinical models used for the assessment of diabetic neuropathy. - Tanishk Saini;Papiya Mitra Mazumder - Naunyn-Schmiedeberg's archives of pharmacology (2024)
6. Pump-Less, Recirculating Organ-on-Chip (rOoC) Platform to Model the Metabolic Crosstalk between Islets and Liver. - Aleksandra Aizenshtadt;Chencheng Wang;Shadab Abadpour;Pedro Duarte Menezes;Ingrid Wilhelmsen;Andrea Dalmao-Fernandez;Justyna Stokowiec;Alexey Golovin;Mads Johnsen;Thomas M D Combriat;Hanne Røberg-Larsen;Nikolaj Gadegaard;Hanne Scholz;Mathias Busek;Stefan J K Krauss - Advanced healthcare materials (2024)
7. Revolutionizing biomedical research: The imperative need for heart-kidney-connected organoids. - Sun-Sook Song;Hun-Jun Park;Yong Kyun Kim;Sun-Woong Kang - APL bioengineering (2024)
8. On the limits of 16S rRNA gene-based metagenome prediction and functional profiling. - Monica Steffi Matchado;Malte Rühlemann;Sandra Reitmeier;Tim Kacprowski;Fabian Frost;Dirk Haller;Jan Baumbach;Markus List - Microbial genomics (2024)
9. Advances in secondary prevention mechanisms of macrovascular complications in type 2 diabetes mellitus patients: a comprehensive review. - Huifang Guan;Jiaxing Tian;Ying Wang;Ping Niu;Yuxin Zhang;Yanjiao Zhang;Xinyi Fang;Runyu Miao;Ruiyang Yin;Xiaolin Tong - European journal of medical research (2024)
10. Advanced 3D imaging and organoid bioprinting for biomedical research and therapeutic applications. - Sushila Maharjan;Chenshuo Ma;Bibhor Singh;Heemin Kang;Gorka Orive;Junjie Yao;Yu Shrike Zhang - Advanced drug delivery reviews (2024)

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