ECM modulated early kidney development in embryonic organ culture

Sebinger, David Daniel Raphael; Ofenbauer, Andreas; Gruber, Petra; Malik, S; Werner, Carsten

doi:10.1016/j.biomaterials.2013.05.031

Cited by 26 publications

(21 citation statements)

References 65 publications

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“…Native and decellularized kidneys were stained for type IV collagen, the most abundant component of the kidney ECM, or laminin, an important component of the basement membrane that supports tubule formation and kidney development (24). Though some loss of collagen IV was expected, and identified across all strategies given the tight balance between cell removal and matrix preservation, Triton/SDS resulted in the smallest loss of collagen IV staining, noted predominantly within the glomeruli (Figure 6 A–D) and along the kidney capsule (not shown) with less surrounding renal tubules.…”

Section: Resultsmentioning

confidence: 99%

Optimization and Critical Evaluation of Decellularization Strategies to Develop Renal Extracellular Matrix Scaffolds as Biological Templates for Organ Engineering and Transplantation

Caralt

Uzarski²,

Iacob³

et al. 2015

American Journal of Transplantation

193

188

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The ability to generate patient-specific cells through induced pluripotent stem cell (iPSC) technology has encouraged development of three-dimensional extracellular matrix (ECM) scaffolds as bioactive substrates for cell differentiation with the long-range goal of bioengineering organs for transplantation. Perfusion decellularization uses the vasculature to remove resident cells, leaving an intact ECM template wherein new cells grow; however, a rigorous evaluative framework assessing ECM structural and biochemical quality is lacking. To address this, we developed histologic scoring systems to quantify fundamental characteristics of decellularized rodent kidneys: ECM structure (tubules, vessels, glomeruli) and cell removal. We also assessed growth factor retention—indicating matrix biofunctionality. These scoring systems evaluated three strategies developed to decellularize kidneys (1% Triton X-100, 1% Triton X-100/0.1% sodium dodecyl sulfate (SDS), and 0.02% Trypsin-0.05% EGTA/1% Triton X-100). Triton and Triton/SDS preserved renal microarchitecture and retained matrix-bound bFGF and VEGF. Trypsin caused structural deterioration and growth factor loss. Triton/SDS-decellularized scaffolds maintained three hours of leak-free blood flow in a rodent transplantation model and supported repopulation with human iPSC-derived endothelial cells and tubular epithelial cells ex vivo. Taken together, we identify an optimal Triton/SDS-based decellularization strategy that produces a biomatrix that may ultimately serve as a rodent model for kidney bioengineering.

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Section: Resultsmentioning

confidence: 99%

Optimization and Critical Evaluation of Decellularization Strategies to Develop Renal Extracellular Matrix Scaffolds as Biological Templates for Organ Engineering and Transplantation

Caralt

Uzarski²,

Iacob³

et al. 2015

American Journal of Transplantation

193

188

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“…Nephrogenesis is impaired in renal explants grown in dissolved collagen IV (Sebinger et al, 2013). Collagen IV is aberrantly expressed in Foxd1 −/− kidneys (Fig.…”

Section: P<96×10mentioning

confidence: 99%

FOXD1 promotes nephron progenitor differentiation by repressing decorin in the embryonic kidney

et al. 2014

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Forkhead transcription factors are essential for diverse processes in early embryonic development and organogenesis. Foxd1 is required during kidney development and its inactivation results in failure of nephron progenitor cell differentiation. Foxd1 is expressed in interstitial cells adjacent to nephron progenitor cells, suggesting an essential role for the progenitor cell niche in nephrogenesis. To better understand how cortical interstitial cells in general, and FOXD1 in particular, influence the progenitor cell niche, we examined the differentiation states of two progenitor cell subtypes in Foxd1 −/− tissue. We found that although nephron progenitor cells are retained in a primitive CITED1-expressing compartment, cortical interstitial cells prematurely differentiate. To identify pathways regulated by FOXD1, we screened for target genes by comparison of Foxd1 null and wild-type tissues. We found that the gene encoding the small leucine-rich proteoglycan decorin (DCN) is repressed by FOXD1 in cortical interstitial cells, and we show that compound genetic inactivation of Dcn partially rescues the failure of progenitor cell differentiation in the Foxd1 null. We demonstrate that DCN antagonizes BMP/SMAD signaling, which is required for the transition of CITED1-expressing nephron progenitor cells to a state that is primed for WNT-induced epithelial differentiation. On the basis of these studies, we propose a mechanism for progenitor cell retention in the Foxd1 null in which misexpressed DCN produced by prematurely differentiated interstitial cells accumulates in the extracellular matrix, inhibiting BMP7-mediated transition of nephron progenitor cells to a compartment in which they can respond to epithelial induction signals.

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“…Thus during mouse kidney development, the maximal amounts of HA are found concomitantly with the onset of the tubular branching process at day 11, and thereafter, HA abundance decreases until birth (5). In in vitro morphogenesis assays, addition of HA to the collagen matrix was reported to enhance tubule formation and branching by renal or mammary gland cells or organ cultures (11,38,48) These studies indicated that enrichment of the ECM with exogenously added HA (arguably mimicking in vivo HA deposition by stromal fibroblasts) can promote epithelial tubulogenesis. We considered it likely, however, that localized secretion of HA by the epithelial cells themselves might be more relevant to the process of branching tubulogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have supported a role for HA in the development of epithelial organs such as the prostate gland (19) and kidney (38,43,48). However, it has not been established whether endogenously produced HA is actually necessary for tubule formation.…”

mentioning

confidence: 99%

Spatially restricted hyaluronan production by Has2 drives epithelial tubulogenesis in vitro

Soulié

Chassot

Ernandez

et al. 2014

American Journal of Physiology-Cell Physiology

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Soulié P, Chassot A, Ernandez T, Montesano R, Féraille E. Spatially restricted hyaluronan production by Has2 drives epithelial tubulogenesis in vitro. Am J Physiol Cell Physiol 307: C745-C759, 2014. First published August 27, 2014; doi:10.1152/ajpcell.00047.2014.-Generation of branched tubes from an epithelial bud is a fundamental process in development. We hypothesized that induction of hyaluronan synthase (Has) and production of hyaluronan (HA) drives tubulogenesis in response to morphogenetic cytokines. Treatment of J3B1A mammary cells with transforming growth factor-␤1 or renal MDCK and mCCD-N21 cells with hepatocyte growth factor induced strong and specific expression of Has2. Immunostaining revealed that HA was preferentially produced at the tips of growing tubules. Inhibition of HA production, either by 4-methylumbelliferone (4-MU) or by Has2 mRNA silencing, abrogated tubule formation. HA production by J3B1A and mCCD-N21 cells was associated with sustained activation of ERK and S6 phosphorylation. However, silencing of either CD44 or RHAMM (receptor for HA-mediated motility), the major HA receptors, by RNA interference, did not alter tubulogenesis, suggesting that this process is not receptor-mediated. epithelial morphogenesis; hyaluronan; tubulogenesis; 3-D cell culture

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ECM modulated early kidney development in embryonic organ culture

Cited by 26 publications

References 65 publications

Optimization and Critical Evaluation of Decellularization Strategies to Develop Renal Extracellular Matrix Scaffolds as Biological Templates for Organ Engineering and Transplantation

Optimization and Critical Evaluation of Decellularization Strategies to Develop Renal Extracellular Matrix Scaffolds as Biological Templates for Organ Engineering and Transplantation

FOXD1 promotes nephron progenitor differentiation by repressing decorin in the embryonic kidney

Spatially restricted hyaluronan production by Has2 drives epithelial tubulogenesis in vitro

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