Kidney development and function: ECM cannot be ignored

Fatemeh, Abdollahzadeh; Rad, Niloofar Khoshdel; Moghadasali, Reza

doi:10.1016/j.diff.2022.02.001

Cited by 5 publications

(3 citation statements)

References 152 publications

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“…37 Collagen gels, due to the focal kinase pathway (FAK), played a fundamental role in epithelial morphogenesis 40 through conduction of mechanical stimuli. [40][41][42] Therefore, we cultured and expanded ELCs on collagen (Figure 1B). In this study, we also used Matrigel ECM for MLCs expansion (Figure 3B).…”

Section: Discussionmentioning

confidence: 99%

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Enhancing maturity in 3D kidney micro‐tissues through clonogenic cell combinations and endothelial integration

Abdollahzadeh,

Khoshdel‐Rad,

Bahrehbar

et al. 2024

J Cellular Molecular Medi

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As an advance laboratory model, three‐dimensional (3D) organoid culture has recently been recruited to study development, physiology and abnormality of kidney tissue. Micro‐tissues derived from primary renal cells are composed of 3D epithelial structures representing the main characteristics of original tissue. In this research, we presented a simple method to isolate mouse renal clonogenic mesenchymal (MLCs) and epithelial‐like cells (ELCs). Then we have done a full characterization of MLCs using flow cytometry for surface markers which showed that more than 93% of cells expressed these markers (Cd44, Cd73 and Cd105). Epithelial and stem/progenitor cell markers characterization also performed for ELC cells and upregulating of these markers observed while mesenchymal markers expression levels were not significantly increased in ELCs. Each of these cells were cultured either alone (ME) or in combination with human umbilical vein endothelial cells (HUVECs) (MEH; with an approximate ratio of 10:5:2) to generate more mature kidney structures. Analysis of 3D MEH renal micro‐tissues (MEHRMs) indicated a significant increase in renal‐specific gene expression including Aqp1 (proximal tubule), Cdh1 (distal tubule), Umod (loop of Henle), Wt1, Podxl and Nphs1 (podocyte markers), compared to those groups without endothelial cells, suggesting greater maturity of the former tissue. Furthermore, ex ovo transplantation showed greater maturation in the constructed 3D kidney.

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Section: Discussionmentioning

confidence: 99%

“…Additionally, several ECM has been shown to support and associate with epithelial and stem cell behaviours 37 . Collagen gels, due to the focal kinase pathway (FAK), played a fundamental role in epithelial morphogenesis 40 through conduction of mechanical stimuli 40–42 . Therefore, we cultured and expanded ELCs on collagen (Figure 1B).…”

Section: Discussionmentioning

confidence: 99%

Enhancing maturity in 3D kidney micro‐tissues through clonogenic cell combinations and endothelial integration

Abdollahzadeh,

Khoshdel‐Rad,

Bahrehbar

et al. 2024

J Cellular Molecular Medi

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“…Kidney ECM is composed of elastin, glycoprotein, proteoglycan, and collagen network-forging interstitial and basal matrices [ 157 ]. Chronic kidney disease patients have been observed to have calcification of ECM in soft tissues [ 158 ].…”

Section: Extracellular Matrix Dynamics During Aging and Longevitymentioning

confidence: 99%

Extracellular Matrix Dynamics as an Emerging yet Understudied Hallmark of Aging and Longevity

2023

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The biomechanical properties of extracellular matrices (ECM) and their consequences for cellular homeostasis have recently emerged as a driver of aging. Here we review the age-dependent deterioration of ECM in the context of our current understanding of the aging processes. We discuss the reciprocal interactions of longevity interventions with ECM remodeling. And the relevance of ECM dynamics captured by the matrisome and the matreotypes associated with health, disease, and longevity. Furthermore, we highlight that many established longevity compounds promote ECM homeostasis. A large body of evidence for the ECM to qualify as a hallmark of aging is emerging, and the data in invertebrates is promising. However, direct experimental proof that activating ECM homeostasis is sufficient to slow aging in mammals is lacking. We conclude that further research is required and anticipate that a conceptual framework for ECM biomechanics and homeostasis will provide new strategies to promote health during aging.

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3D Humanized Bioprinted Tubulointerstitium Model to Emulate Renal Fibrosis In Vitro

Addario,

Fernández‐Pérez,

Formica

et al. 2024

Adv Healthcare Materials

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Chronic kidney disease (CKD) leads to a gradual loss of kidney function, with fibrosis as pathological endpoint, which is characterized by extracellular matrix (ECM) deposition and remodeling. Traditionally, in vivo models are used to study interstitial fibrosis, through histological characterization of biopsy tissue. However, ethical considerations and the 3Rs (replacement, reduction, and refinement) regulations emphasizes the need for humanized 3D in vitro models. This study introduces a bioprinted in vitro model which combines primary human cells and decellularized and partially digested extracellular matrix (ddECM). A protocol was established to decellularize kidney pig tissue and the ddECM was used to encapsulate human renal cells. To investigate fibrosis progression, cells were treated with transforming growth factor beta 1 (TGF‐β1), and the mechanical properties of the ddECM hydrogel were modulated using vitamin B2 crosslinking. The bioprinting perfusable model replicates the renal tubulointerstitium. Results show an increased Young's modulus over time, together with the increase of ECM components and cell dedifferentiation toward myofibroblasts. Multiple fibrotic genes resulted upregulated, and the model closely resembled fibrotic human tissue in terms of collagen deposition. This 3D bioprinted model offers a more physiologically relevant platform for studying kidney fibrosis, potentially improving disease progression research and high‐throughput drug screening.

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Kidney development and function: ECM cannot be ignored

Cited by 5 publications

References 152 publications

Enhancing maturity in 3D kidney micro‐tissues through clonogenic cell combinations and endothelial integration

Enhancing maturity in 3D kidney micro‐tissues through clonogenic cell combinations and endothelial integration

Extracellular Matrix Dynamics as an Emerging yet Understudied Hallmark of Aging and Longevity

3D Humanized Bioprinted Tubulointerstitium Model to Emulate Renal Fibrosis In Vitro

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