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Analysis of structural components of decellularized scaffolds in renal fibrosis.

ABSTRACT: Chronic kidney disease has been recognized as a major public health problem worldwide and renal fibrosis is a common pathological process occurring in chronic renal failure. It is very promising to find the strategies to slow or even prevent the progression of fibrosis. This study focused on whether renal fibrosis decellularized scaffolds has the potential to be a model of cellular mechanisms of tissue fibrosis or donors for tissue engineering. In order to evaluate the feasibility of decellularized scaffolds derived from pathological kidneys, histology, proteomics and ELISA will be used to analysis the changes in the structure and main components of fibrotic tissue. The fibrosis model in this paper was induced by adenine-fed and the results showed that the structure of fibrotic scaffold was changed and some protein were up-regulated or down-regulated, but the cytokines associated with renal regeneration after injury were remained. In cell experiments, endothelial progenitor cells proliferated well, which proved that the fibrotic scaffolds have non-cytotoxic. All these conclusions indicate that the renal fibrosis decellularized scaffolds model has the ability to study fibrosis mechanism and the potential to be engineering donors as well as normal scaffolds.

SUBMITTER: Zhang R

PROVIDER: S-EPMC7815494 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Analysis of structural components of decellularized scaffolds in renal fibrosis.

Zhang Rui R Jiang Junqun J Yu Yaling Y Wang Fangfang F Gao Niuniu N Zhou Yingjie Y Wan Xinlong X Wang Zhibin Z Wei Peng P Mei Jin J

Bioactive materials 20210116 7

Chronic kidney disease has been recognized as a major public health problem worldwide and renal fibrosis is a common pathological process occurring in chronic renal failure. It is very promising to find the strategies to slow or even prevent the progression of fibrosis. This study focused on whether renal fibrosis decellularized scaffolds has the potential to be a model of cellular mechanisms of tissue fibrosis or donors for tissue engineering. In order to evaluate the feasibility of decellulari ...[more]

PMID: 33511316

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Project description:Whole tooth regeneration approaches currently are limited by our inability to bioengineer full-sized, living replacement teeth. Recently, decellularized organ scaffolds have shown promise for applications in regenerative medicine by providing a natural extracellular matrix environment that promotes cell attachment and tissue-specific differentiation leading to full-sized organ regeneration. We hypothesize that decellularized tooth buds (dTBs) created from unerupted porcine tooth buds (TBs) can be used to guide reseeded dental cell differentiation to form whole bioengineered teeth, thereby providing a potential off-the-shelf scaffold for whole tooth regeneration. Porcine TBs were harvested from discarded 6-mo-old pig jaws, and decellularized by successive sodium dodecyl sulfate/Triton-X cycles. Four types of replicate implants were used in this study: 1) acellular dTBs; 2) recellularized dTBs seeded with porcine dental epithelial cells, human dental pulp cells, and human umbilical vein endothelial cells (recell-dTBs); 3) dTBs seeded with bone morphogenetic protein (BMP)-2 (dTB-BMPs); and 4) freshly isolated nondecellularized natural TBs (nTBs). Replicate samples were implanted into the mandibles of host Yucatan mini-pigs and grown for 3 or 6 mo. Harvested mandibles with implanted TB constructs were fixed in formalin, decalcified, embedded in paraffin, sectioned, and analyzed via histological methods. Micro-computed tomography (CT) analysis was performed on harvested 6-mo samples prior to decalcification. All harvested constructs exhibited a high degree of cellularity. Significant production of organized dentin and enamel-like tissues was observed in dTB-recell and nTB implants, but not in dTB or dTB-BMP implants. Micro-CT analyses of 6-mo implants showed the formation of organized, bioengineered teeth of comparable size to natural teeth. To our knowledge, these results are the first to describe the potential use of dTBs for functional whole tooth regeneration.

Project description:The authors have previously shown that acellular (AC) trachea-lung scaffolds can (1) be produced from natural rat lungs, (2) retain critical components of the extracellular matrix (ECM) such as collagen-1 and elastin, and (3) be used to produce lung tissue after recellularization with murine embryonic stem cells. The aim of this study was to produce large (porcine or human) AC lung scaffolds to determine the feasibility of producing scaffolds with potential clinical applicability. We report here the first attempt to produce AC pig or human trachea-lung scaffold. Using a combination of freezing and sodium dodecyl sulfate washes, pig trachea-lungs and human trachea-lungs were decellularized. Once decellularization was complete we evaluated the structural integrity of the AC lung scaffolds using bronchoscopy, multiphoton microscopy (MPM), assessment of the ECM utilizing immunocytochemistry and evaluation of mechanics through the use of pulmonary function tests (PFTs). Immunocytochemistry indicated that there was loss of collagen type IV and laminin in the AC lung scaffold, but retention of collagen-1, elastin, and fibronectin in some regions. MPM scoring was also used to examine the AC lung scaffold ECM structure and to evaluate the amount of collagen I in normal and AC lung. MPM was used to examine the physical arrangement of collagen-1 and elastin in the pleura, distal lung, lung borders, and trachea or bronchi. MPM and bronchoscopy of trachea and lung tissues showed that no cells or cell debris remained in the AC scaffolds. PFT measurements of the trachea-lungs showed no relevant differences in peak pressure, dynamic or static compliance, and a nonrestricted flow pattern in AC compared to normal lungs. Although there were changes in content of collagen I and elastin this did not affect the mechanics of lung function as evidenced by normal PFT values. When repopulated with a variety of stem or adult cells including human adult primary alveolar epithelial type II cells both pig and human AC scaffolds supported cell attachment and cell viability. Examination of scaffolds produced using a variety of detergents indicated that detergent choice influenced human immune response in terms of T cell activation and chemokine production.

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Analysis of structural components of decellularized scaffolds in renal fibrosis.

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Analysis of structural components of decellularized scaffolds in renal fibrosis.

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