Thiol-ene cross-linked alginate hydrogel encapsulation modulates the extracellular matrix of kidney organoids by reducing abnormal type 1a1 collagen deposition
bioRxiv (Cold Spring Harbor Laboratory)
Abstract
ABSTRACT Differentiated kidney organoids from induced pluripotent stem cells hold promise as a treatment for patients with kidney diseases. Before these organoids can be translated to the clinic, shortcomings regarding their cellular, extracellular compositions and developmental plateau needs to be overcome. We performed a proteomic analysis on kidney organoids cultured for a prolonged culture time and we found a specific change in the extracellular matrix composition with increased expression of types 1a1, 2 and 6a1 collagen. Such an excessive accumulation of specific collagen types is a hallmark of renal fibrosis that causes a life-threatening pathological condition by compromising key functions of the human kidney. Here we hypothesized the need for a three-dimensional environment to grow the kidney organoids, which could better mimic the in vivo surroundings of the developing kidney than standard culture on a transwell filter. Encapsulating organoids for four days in a soft, thiol-ene cross-linked alginate hydrogel resulted in decreased type 1a1 collagen expression. Furthermore, the encapsulation did not result in any changes of organoid structural morphology. Using a biomaterial to modulate collagen expression allows for a prolonged kidney organoid culture in vitro and a reduction of abnormal type 1a1 collagen expression bringing kidney organoids closer to clinical application. HIGHLIGHTS Prolonging kidney organoid culture results in a developmental plateau instead of improved in vitro maturation. Proteomic analyses point to an increased expression of specific collagen subtypes associated with renal fibrosis. Encapsulating kidney organoids using a soft thiol-ene cross-linked alginate hydrogel reduces collagen type 1a1 and αSMA deposition.
Authors 10
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Affiliation as printed
MERLN Institute for Technology-Inspired Regenerative Medicine, Department of Cell Biology–Inspired Tissue Engineering, Maastricht University, Maastricht, the Netherlands
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Affiliation as printed
MERLN Institute for Technology-Inspired Regenerative Medicine, Department of Cell Biology–Inspired Tissue Engineering, Maastricht University, Maastricht, the Netherlands
MERLN Institute for Technology-Inspired Regenerative Medicine, Department of Complex Tissue Regeneration, Maastricht University, Maastricht, the Netherlands
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Affiliation as printed
MERLN Institute for Technology-Inspired Regenerative Medicine, Department of Cell Biology–Inspired Tissue Engineering, Maastricht University, Maastricht, the Netherlands
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Affiliation as printed
MERLN Institute for Technology-Inspired Regenerative Medicine, Department of Complex Tissue Regeneration, Maastricht University, Maastricht, the Netherlands
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Affiliation as printed
MERLN Institute for Technology-Inspired Regenerative Medicine, Department of Cell Biology–Inspired Tissue Engineering, Maastricht University, Maastricht, the Netherlands
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Loes E. Wiersma Aachen Department of Internal Medicine - Nephrology Einthoven Laboratory of Vascular and Regenerative Medicine
Leiden University Medical Center
Affiliation as printed
Department of Internal Medicine - Nephrology, Leiden University Medical Center, Leiden, the Netherlands
Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, the Netherlands
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Cathelijne W. van den Berg Aachen Department of Internal Medicine - Nephrology Einthoven Laboratory of Vascular and Regenerative Medicine
Leiden University Medical Center
Affiliation as printed
Department of Internal Medicine - Nephrology, Leiden University Medical Center, Leiden, the Netherlands
Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, the Netherlands
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Ton J. Rabelink Aachen Department of Internal Medicine - Nephrology Einthoven Laboratory of Vascular and Regenerative Medicine
Leiden University Medical Center
Affiliation as printed
Department of Internal Medicine - Nephrology, Leiden University Medical Center, Leiden, the Netherlands
Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, the Netherlands
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Matthew Brandon Baker corresponding
Affiliation as printed
MERLN Institute for Technology-Inspired Regenerative Medicine, Department of Complex Tissue Regeneration, Maastricht University, Maastricht, the Netherlands
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Vanessa L.S. LaPointe corresponding
Affiliation as printed
MERLN Institute for Technology-Inspired Regenerative Medicine, Department of Cell Biology–Inspired Tissue Engineering, Maastricht University, Maastricht, the Netherlands
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