Bioengineering and vascularization strategies for islet organoids: advancing toward diabetes therapy

Yang, Jing; Yan, Yuxin; Yin, Xiya; Liu, Xiangqi; Reshetov, Igor V.; Karalkin, Pavel A.; Li, Qingfeng; Huang, Ru-Lin

doi:10.1016/j.metabol.2024.155786

Cited by 4 publications

(3 citation statements)

References 154 publications

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“…A better mechanistic understanding of adaptation may lead to more realistic algorithms for network generation. Such algorithms are becoming more and more relevant for setting up digital twins and in silico trials [37], while unraveling mechanisms of network adaptation is also of increasing relevance for developing perfused artificial organs [38].…”

Section: Discussionmentioning

confidence: 99%

Arterial arcades and collaterals regress under hemodynamics-based diameter adaptation: a computational and mathematical analysis

Rottschäfer,

Kuppers,

Chen

et al. 2024

Preprint

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Segments in the arterial network have a >1000-fold span of radii. This is believed to result from adaptation of each segment to the wall shear stress (WSS), with outward respectively inward remodeling if WSS is higher or lower than some reference value. While this seems a straightforward mechanism for arterial tree design, the arterial network is not a tree but contains numerous arcades, collaterals and other looping structures. In this theoretical study, we analyzed stability of looping structures in arterial networks under WSS control.Simulation models were based on very simple network topologies as well as on published human coronary and mouse cerebral arterial networks. Adaptation was implemented as a rate of change of structural radius of each segment that is proportional to the deviation from its reference WSS. A more generalized model was based on adaptation to a large range of other local hemodynamic stimuli, including velocity, flow and power dissipation.For over 12,000 tested parameter sets, the simulations invariably predicted loss of loops due to regression of one or more of the segments. In the small networks, this was the case for both the WSS and the generalized model, and for a large range of initial conditions and model parameters. Loss of loopiness also was predicted by models that included direction-dependent adaptation rates, heterogeneous reference WSS or adaptation rates among the adapting segments, and adaptation under dynamic conditions. Loss of loops was also found in the coronary and cerebral artery networks subjected to adaptation to WSS.In a mathematical analysis we proved that loss of loops is a direct consequence of Kirchhoff’s circuit law, which for each loop leads to a positive eigenvalue in the Jacobian matrix of partial derivatives in the adaptation model, and therefore to unstable equilibria in the presence of loops.Loss of loops is an inherent property of arterial networks that adapt to local hemodynamics. Additional mechanisms are therefore needed to explain their presence, including direct communication between connected segments.

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Section: Discussionmentioning

confidence: 99%

Arterial arcades and collaterals regress under hemodynamics-based diameter adaptation: a computational and mathematical analysis

Rottschäfer,

Kuppers,

Chen

et al. 2024

Preprint

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“…The defects in the overall function of islet organoids may also be associated with factors like the vascularization levels, the composition and arrangement of EC cells, and the heterogeneity of β-cells. Insufficient vascularization hampers β-cell maturation, severely compromising its function : hypoxic stress and nutrient deficiencies can lead to cell apoptosis and hypoplasia, while inhibited intercellular signaling between vascular and β-cells interferes with the normal regulation of metabolic waste removal and humoral response [ 125 ]. Most islet organoids consist of primarily β-cells, with α, β, δ, and auxiliary cells making up only a minor fraction.…”

Section: Challenges In Construction and Application Of Islet Organoidmentioning

confidence: 99%

“…In addition to insufficient vascularization and endothelial function defects [ 125 ], organoid culture scaffolds are prone to thrombosis, which would severely reduce the viability of transplanted organoids [ 151 ]. This may be due to poor anticoagulation and biomechanical properties of the scaffolds, as well as the exposure to scaffold collagen promoting coagulation after reperfusion.…”

Section: Challenges In Construction and Application Of Islet Organoidmentioning

confidence: 99%

Ameliorating and refining islet organoids to illuminate treatment and pathogenesis of diabetes mellitus

Li,

Xu,

Chen

et al. 2024

Stem Cell Res Ther

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Diabetes mellitus, a significant global public health challenge, severely impacts human health worldwide. The organoid, an innovative in vitro three-dimensional (3D) culture model, closely mimics tissues or organs in vivo. Insulin-secreting islet organoid, derived from stem cells induced in vitro with 3D structures, has emerged as a potential alternative for islet transplantation and as a possible disease model that mirrors the human body’s in vivo environment, eliminating species difference. This technology has gained considerable attention for its potential in diabetes treatment. Despite advances, the process of stem cell differentiation into islet organoid and its cultivation demonstrates deficiencies, prompting ongoing efforts to develop more efficient differentiation protocols and 3D biomimetic materials. At present, the constructed islet organoid exhibit limitations in their composition, structure, and functionality when compared to natural islets. Consequently, further research is imperative to achieve a multi-tissue system composition and improved insulin secretion functionality in islet organoid, while addressing transplantation-related safety concerns, such as tumorigenicity, immune rejection, infection, and thrombosis. This review delves into the methodologies and strategies for constructing the islet organoid, its application in diabetes treatment, and the pivotal scientific challenges within organoid research, offering fresh perspectives for a deeper understanding of diabetes pathogenesis and the development of therapeutic interventions.

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The efficiency of stem cell differentiation into functional beta cells for treating insulin-requiring diabetes: Recent advances and current challenges

Luo,

Yu,

Liu

2024

Endocrine

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Bioengineering and vascularization strategies for islet organoids: advancing toward diabetes therapy

Cited by 4 publications

References 154 publications

Arterial arcades and collaterals regress under hemodynamics-based diameter adaptation: a computational and mathematical analysis

Arterial arcades and collaterals regress under hemodynamics-based diameter adaptation: a computational and mathematical analysis

Ameliorating and refining islet organoids to illuminate treatment and pathogenesis of diabetes mellitus

The efficiency of stem cell differentiation into functional beta cells for treating insulin-requiring diabetes: Recent advances and current challenges

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