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RETRACTED: Engineered whole organs and complex tissues
Prof Stephen F Badylak, MD, Daniel J Weiss, MD, Prof Arthur Caplan, PhD, Prof Paolo Macchiarini, MD The Lancet Volume 379, Issue 9819, Pages (March 2012) DOI: /S (12) Copyright © 2012 Elsevier Ltd Terms and Conditions
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Figure 1 Organ and tissue bioengineering
The Lancet , DOI: ( /S (12) ) Copyright © 2012 Elsevier Ltd Terms and Conditions
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Figure 2 Key elements of an organ bioreactor
The Lancet , DOI: ( /S (12) ) Copyright © 2012 Elsevier Ltd Terms and Conditions
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Figure 3 Tissue-engineered tracheal transplantation
CT scan of a patent tubular natural human scaffold implanted after removal of the native trachea for malignant disease (A; scan at 1 month) and benign disease (B; three-dimensional reconstruction based on a CT scan at 2 years). Haematoxylin and eosin stain of native (C) and decellularised (E) trachea; after application of 25 detergent–enzymatic cycles, the tracheal matrices were almost completely decellularised and only a few nuclei were still present in the cartilaginous region (arrow shows preserved basement membrane zones). Movat pentachromic staining (connective tissue staining) of the native (D) and decellularised (F) trachea; yellow–orange staining shows collagen and reticulum fibres, green shows mucins, blue–green shows ground substance, and red shows muscle. (G) Endothelial progenitor cells isolated from mobilised peripheral blood and expanded in vitro were able to organise into a meshwork of capillary-like tubules (H), suggesting the boosting effect of the regenerative therapy. Haematoxylin and eosin stain of decellularised trachea 1 year after transplantation (I), showing healthy tracheal epithelium (J). (K) Laminin immunostaining outlining the presence of a continuous layer of basal membrane (arrow) and small blood vessels (asterisks). (L) Transmission electronic micrograph showing the presence of the basal membrane (arrow). The Lancet , DOI: ( /S (12) ) Copyright © 2012 Elsevier Ltd Terms and Conditions
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Figure 4 Tissue-engineered mouse lungs
(A) Haematoxylin and eosin stain of a representative decellularised whole mouse lung and lung slices shows preservation of healthy architecture (magnification ×100). (B) Transmission electron micrograph images of alveolar septa in a representative decellularised whole mouse lung (magnification ×3000). (C–F) Intratracheally inoculated MSCs cultured to 1 month grow in parenchymal and airway regions of decellularised whole mouse lungs; representative photomicrographs (magnification ×100 in [C], ×400 in [D], ×400 in [E], and ×400 in [F]) show MSCs (arrows) in parenchymal lung regions and in airways. The asterisk in (C) shows the region magnified in (D). Vascular perfusion of a decellularised whole rat lung (G); after cannulation of the main pulmonary artery and the left atrium, 1·5% Evans blue dye was injected through the pulmonary artery. Rapid exiting from the left atrium was noted with simultaneous diffusion of dye throughout the lung parenchyma. Representative photomicrographs (magnification ×200) obtained 1 day after cell inoculation into decellularised whole mouse lungs (H–J); different cells localise to different regions of remaining extracellular matrix proteins. Specific fibronectin immunofluorescence is shown in red with 4′-6-diamidino-2-phenylindole (DAPI) nuclear staining in blue. MSCs inoculated into decellularised mouse lungs first localise to regions enriched in fibronectin (H). C10 mouse lung epithelial cells do not localise to regions enriched in fibronectin (I). Blocking the α5 integrin on MSCs with a neutralising antibody before cell inoculation results in MSCs localising in areas not enriched with fibronectin (J). MSC=mesenchymal stromal cell. The Lancet , DOI: ( /S (12) ) Copyright © 2012 Elsevier Ltd Terms and Conditions
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