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Comparative Decellularization and Recellularization of Wild-Type and Alpha 1,3 Galactosyltransferase Knockout Pig Lungs : A Model for Ex Vivo Xenogeneic Lung Bioengineering and Transplantation
Background: A novel potential approach for lung transplantation could be to utilize xenogeneic decellularized pig lung scaffolds that are recellularized with human lung cells. However, pig tissues express several immunogenic proteins, notably galactosylated cell surface glycoproteins resulting from alpha 1,3 galactosyltransferase (α-gal) activity, that could conceivably prevent effective use. Use
A Computational Model of Cellular Engraftment on Lung Scaffolds
The possibility that stem cells might be used to regenerate tissue is now being investigated for a variety of organs, but these investigations are still essentially exploratory and have few predictive tools available to guide experimentation. We propose, in this study, that the field of lung tissue regeneration might be better served by predictive tools that treat stem cells as agents that obey ce
Heat transfer in laminar flows of extended modified power law fluids in rectangular ducts
This paper reports the results of a numerical study of the Nusselt number for the H1 and T boundary conditions in laminar, fully-developed flows of pseudoplastic and dilatant fluids in rectangular ducts. Equations for the apparent viscosity that span the entire shear rate range were utilized and the Nusselt numbers were calculated as a function of a shear rate parameter that determines the flow re
A microwave-assisted solution combustion synthesis to produce europium-doped calcium phosphate nanowhiskers for bioimaging applications
Biocompatible nanoparticles possessing fluorescent properties offer attractive possibilities for multifunctional bioimaging and/or drug and gene delivery applications. Many of the limitations with current imaging systems center on the properties of the optical probes in relation to equipment technical capabilities. Here we introduce a novel high aspect ratio and highly crystalline europium-doped c
WISP1 mediates IL-6-dependent proliferation in primary human lung fibroblasts
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease. IPF is characterized by epithelial cell injury and reprogramming, increases in (myo)fibroblasts, and altered deposition of extracellular matrix. The Wnt1-inducible signaling protein 1 (WISP1) is involved in impaired epithelial-mesenchymal crosstalk in pulmonary fibrosis. Here, we aimed to further investigate
Residual Detergent Detection Method for Nondestructive Cytocompatibility Evaluation of Decellularized Whole Lung Scaffolds
The development of reliable tissue engineering methods using decellularized cadaveric or donor lungs could potentially provide a new source of lung tissue. The vast majority of current lung decellularization protocols are detergent based and incompletely removed residual detergents may have a deleterious impact on subsequent scaffold recellularization. Detergent removal and quality control measure
Freshly thawed and continuously cultured human bone marrow-derived mesenchymal stromal cells comparably ameliorate allergic airways inflammation in immunocompetent mice
Recent data suggest that freshly thawed previously frozen mesenchymal stromal cells (MSCs) may not have the same effectiveness or breadth of anti-inflammatory activities as do continuously cultured MSCs. This has significant implications for clinical use, in which many infusion schemes use frozen cells thawed at the bedside for administration. The available data, however, predominantly evaluate in
Preclinical validation and imaging of Wnt-induced repair in human 3D lung tissue cultures
Chronic obstructive pulmonary disease (COPD) is characterised by a progressive loss of lung tissue. Inducing repair processes within the adult diseased lung is of major interest and Wnt/β- catenin signalling represents a promising target for lung repair. However, the translation of novel therapeutic targets from model systems into clinical use remains a major challenge. We generated murine and pat
An official American Thoracic Society workshop report : Stem cells and cell therapies in lung biology and diseases
The University of Vermont College of Medicine and the Vermont Lung Center, in collaboration with the NHLBI, Alpha-1 Foundation, American Thoracic Society, European Respiratory Society, International Society for Cell Therapy, and the Pulmonary Fibrosis Foundation, convened a workshop, "Stem Cells and Cell Therapies in Lung Biology and Lung Diseases, " held July 29 to August 1, 2013 at the Universit
Systemic administration of human bone marrow-derived mesenchymal stromal cell extracellular vesicles ameliorates Aspergillus hyphal extract-induced allergic airway inflammation in immunocompetent mice
An increasing number of studies demonstrate that administration of either conditioned media (CM) or extracellular vesicles (EVs) released by mesenchymal stromal cells (MSCs) derived from bone marrow and other sources are as effective as the MSCs themselves in mitigating inflammation and injury. The goal of the current study was to determine whether xenogeneic administration of CM or EVs from human
Three-dimensional scaffolds of acellular human and porcine lungs for high throughput studies of lung disease and regeneration
Acellular scaffolds from complex whole organs such as lung are being increasingly studied for ex vivo organ generation and for in vitro studies of cell-extracellular matrix interactions. We have established effective methods for efficient de and recellularization of large animal and human lungs including techniques which allow multiple small segments (~1-3 cm3) to be excised that retain 3-dimensio
Comparative decellularization and recellularization of normal versus emphysematous human lungs
Acellular whole human lung scaffolds represent a unique opportunity for ex vivo tissue engineering. However, it remains unclear whether lungs from individuals with chronic lung diseases such as chronic obstructive pulmonary disease (COPD) can be appropriately decellularized and recellularized. To assess this, cadaveric human lungs from normal (non-smoking) patients and from patients with COPD (smo
The effects of storage and sterilization on de-cellularized and re-cellularized whole lung
Despite growing interest on the potential use of de-cellularized whole lungs as 3-dimensional scaffolds for ex vivo lung tissue generation, optimal processing including sterilization and storage conditions, are not well defined. Further, it is unclear whether lungs need to be obtained immediately or may be usable even if harvested several days post-mortem, a situation mimicking potential procureme
The effect of age and emphysematous and fibrotic injury on the re-cellularization of de-cellularized lungs
Use of de-cellularized cadaveric lungs as 3-dimensional scaffolds for ex vivo lung tissue generation offers a new potential therapeutic approach for clinical lung transplantation. However, it is likely that some of the available cadaveric human lungs may be from older donors or from donors with previously existing structural lung diseases such as emphysema or pulmonary fibrosis. It is not known wh
Design and synthesis of an artificial pulmonary pleura for high throughput studies in acellular human lungs
Whole organ decellularization of complex organs, such as lungs, presents a unique opportunity for use of acellular scaffolds for ex vivo tissue engineering or for studying cell-extracellular matrix interactions ex vivo. A growing body of literature investigating decellularizing and recellularizing rodent lungs has provided important proof of concept models and rodent lungs are readily available fo
Can stem cells be used to generate new lungs? Ex vivo lung bioengineering with decellularized whole lung scaffolds
For patients with end-stage lung diseases, lung transplantation is the only available therapeutic option. However, the number of suitable donor lungs is insufficient and lung transplants are complicated by significant graft failure and complications of immunosuppressive regimens. An alternative to classic organ replacement is desperately needed. Engineering of bioartificial organs using either nat
Microwave-assisted solution combustion synthesis of high aspect ratio calcium phosphate nanoparticles
Calcium phosphates (CaPs) are major chemical constituents of mammalian bone. Their osteoconductivity in vitro and in vivo has encouraged their use in biomaterial applications such as implant materials and drug delivery. High aspect ratio nanoparticles are attractive for many biomedical applications; however, precise control of the phase and morphology is challenging. The impact of fuel-to-oxidant
Progress and outlook of inorganic nanoparticles for delivery of nucleic acid sequences related to orthopedic pathologies : A review
The anticipated growth in the aging population will drastically increase medical needs of society; of which, one of the largest components will undoubtedly be from orthopedic-related pathologies. There are several proposed solutions being investigated to cost-effectively prepare for the future-pharmaceuticals, implant devices, cell and gene therapies, or some combination thereof. Gene therapy is o
Cytocompatibility evaluation of microwave sintered biphasic calcium phosphate scaffolds synthesized using pH control
Compounds belonging to the calcium phosphate (CaP) system are known to be major constituents of bone and are bioactive to different extents in vitro and in vivo. Their chemical similarity makes them prime candidates for implants and bone tissue engineering scaffolds. CaP nanoparticles of amorphous hydroxyapatite (aHA) and dicalcium phosphate dihydrate (DCPD) were synthesized using chemical precipi
