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PubMed1993

Thymoma--morphologic subclassification correlates with invasiveness and immunohistologic features: a study of 122 cases.

We applied the classification system of Marino and Müller-Hermelink (Virchows Arch A Pathol Anat Histopathol 407:119-149, 1985) and Kirchner and Müller-Hermelink (Prog Surg Pathol 10: 167-189, 1989) to 122 thymic epithelial tumors to evaluate the utility of this classification and to determine its correlation with invasiveness, follicular lymphoid hyperplasia, myasthenia gravis, and immunophenotype. The majority of cases could be classified according to this scheme: eight cases (7%) were medullary thymoma, 34 cases (28%) were mixed thymoma, 20 cases (16%) were predominantly cortical (organoid) thymoma, 22 cases (18%) were cortical thymoma, 32 cases (26%) were well-differentiated carcinoma (WDC), two cases (2%) were high-grade carcinoma, and four cases (3%) were unclassifiable. We report a detailed histologic analysis of these subtypes, with criteria for diagnosis. We propose that the term "organoid thymoma" be replaced by "predominantly cortical thymoma." We also observed a previously unrecognized subtype of WDC with spindle-shaped epithelial cells, which must be distinguished from medullary thymoma. There was a strong correlation between histologic subtype and invasion (P < .0001). All medullary and mixed thymomas were either completely encapsulated (64%) or had only invasion through the capsule (36%). Organoid and cortical thymomas showed an intermediate degree of invasiveness, with 36% invasive into mediastinal fat and 14% into adjacent structures. All the cases of WDC were invasive either through the capsule (19%) or into adjacent structures (81%); five cases (16%) also showed distant spread in the form of pleural seeding (four cases) or lymph node metastasis (one case). Microscopic evaluation disclosed invasion in a substantial number of cases (28.5%) thought by the surgeon to be encapsulated. The presence of follicular lymphoid hyperplasia, either within the tumor, in the residual normal thymus, or in both, was a significant predictor of myasthenia gravis (P < .0015); there was an increased association of myasthenia gravis and thymomas with cortical type epithelium (organoid thymoma, cortical thymoma, and WDC). There was no correlation between epithelial cell morphology and antigen expression; however, the immunophenotype of the associated lymphocytes corresponded closely to the morphologic classification of the thymomas. The Müller-Hermelink morphologic classification can be applied to most cases of thymoma and strongly predicts invasive behavior. The correlation of lymphocyte immunophenotype with the morphologic classification of the epithelial cells suggests that it is biologically accurate.

Adolescent↗
PubMed2026

Tissue-derived extracellular matrix hydrogels instruct epigenetic adaptation in metastatic colonization.

The extracellular matrix (ECM) plays a central role in regulating tumor progression and metastatic colonization by providing biochemical and mechanical signals that shape cancer cell fate. However, most organoid culture systems rely on basement membrane extracts that fail to reproduce the tissue-specific extracellular environments encountered during metastasis. Here, we develop tissue-derived decellularized matrix hydrogels to reconstruct organ-specific microenvironments and investigate epigenetic adaptation to ECM cues during metastatic colonization. Patient-derived colorectal cancer organoids cultured in colon-derived matrices exhibited enhanced maintenance of stem-like phenotypes and colon-specific chromatin accessibility landscapes compared with cultures grown in basement membrane extracts, demonstrating improved physiological relevance for primary tumor modeling. When exposed to matrices derived from secondary organs, the organoids showed distinct growth phenotypes accompanied by rapid, tissue-dependent chromatin accessibility remodeling, indicating that ECM composition alone can reshape regulatory programs governing metastatic adaptation. Notably, liver-derived matrices selectively activated hepatocyte nuclear factor 4 alpha (HNF4A)-associated transcriptional networks and created a context-specific dependence on c-MET signaling for survival. Functional perturbation of HNF4A or c-MET signaling confirmed that both are required for organoid formation specifically within the liver matrix environment. Together, these findings establish tissue-derived matrix hydrogels as instructive bioactive materials that actively regulate cancer cell epigenetic states and reveal microenvironment-specific therapeutic vulnerabilities during early metastatic colonization.

Journal Article↗
PubMed1999

Xenotransplantation of fetal porcine hepatocytes in rats using a tissue engineering approach.

Hepatocytes can be successfully transplanted into highly vascular sites such as the spleen, liver, and lungs. Subcutaneous sites lack adequate vascularization to nutritionally support transplanted hepatocytes. We recently reported that matrix-immobilized angiogenic growth factors, e.g., endothelial cell growth factor (ECGF), can induce a high degree of neovascularization. Using this technique, we explored the possibility of transplanting isolated fetal porcine hepatocytes to create liver tissue organoids at a specific subcutaneous site. We evaluated chitosan as a scaffold biomaterial because of its structural similarity to glycosaminoglycans; glycosaminoglycans play a critical role in cell attachment, differentiation, and morphogenesis. Freshly isolated fetal porcine hepatocytes (FPH) (viability greater than 97%) were cultured on modified chitosan scaffolds and transplanted into rat groin fat pads with or without ECGF-induced neovascularization. Cell density and attachment kinetics on chitosan were examined by scanning electron microscopy (SEM) and quantified using a flavianic acid binding assay. Hepatocyte viability and liver organoid formation were examined immunohistochemically. FPH transplanted without prior neovascularization died within 1 day post-transplantation. When transplanted after ECGF-induced neovascularization, FPH thrived for at least 2 weeks and formed liver tissue like structures. Immunohistochemical analysis revealed the presence of hepatocyte-specific cytokeratin staining as well as the presence of alpha-fetoprotein. Light microscopy and SEM revealed that FPH did not change their morphology after attachment to the chitosan surfaces. Thus, chitosan-based biomaterial surfaces have good hepatocyte attachment properties. However, extensive neovascularization is essential for hepatocyte survival and organoid formation. In the future, chitosan-based biomaterials may be useful as scaffolds for creating liver tissue organoids.

Animals↗
PubMed2005

A novel organotypic culture model for normal human endometrium: regulation of epithelial cell proliferation by estradiol and medroxyprogesterone acetate.

BACKGROUND: A novel organotypic culture system was established for modelling the hormonal responses of the normal human endometrium in vitro. METHODS: Endometrial epithelial cells were cultured as glandular organoids within reconstituted extracellular matrix (Matrigel) in tissue culture inserts and stromal cells on plastic below the epithelial compartment. The effects of estradiol (E2) and E2 together with medroxyprogesterone acetate (MPA) on cell proliferation and the expression of estrogen receptor alpha (ERalpha) and progesterone receptor (PR) were studied in 10 epithelial-stromal co-cultures and in three parallel monocultures of epithelial organoids. RESULTS: In co-cultures, E2 was shown to increase the percentage of Ki67-positive cells by approximately 2-fold relative to untreated controls. In the presence of MPA, a significant decrease in cell proliferation was detected. Similar results were obtained when the corresponding percentages of Ki67-positive organoids were calculated instead of individual cells. In the absence of stromal fibroblasts, Ki67 epithelial labelling remained below the control value after both hormonal treatments. Epithelial organoids retained their capacity to express estrogen and progesterone receptors in culture. E2 was shown to markedly increase and MPA to down-regulate the expression of PR. The expression of ERalpha was only slightly affected by either hormonal treatment. CONCLUSIONS: The present organotypic model provides a novel in vitro system in which to study the effects of steroids in the normal human endometrium both in terms of cell proliferation and gene expression. The culture system holds promise as a useful method to screen novel steroid compounds and may help to circumvent problems related to the use of animal models.

Antineoplastic Agents, Hormonal↗
PubMed1995

Correlation of surfactant phosphatidylcholine synthesis and 11 beta-hydroxysteroid dehydrogenase in the fetal lung.

Glucocorticosteroids (GCS) are prerequisite for the induction of surfactant synthesis in the fetal lung. The 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) regulates the intracellular concentration of biologically active GCS. In this study we demonstrate the correlation of 11 beta-HSD activity and the GCS-induced surfactant phosphatidylcholine synthesis in organoid cultures of fetal rat lung. In the first series of experiments, [3H]corticosterone (CORT) or [3H]11-dehydrocorticosterone (11-DHC) were added to lung organoid cultures to test 11 beta-HSD activity. We found a low oxidative and a high reductive conversion indicating that in intact cells the equilibrium tends to biologically active GCS. However, in homogenized organoid cultures oxidative outweighed reductive activity. Secondly, the phosphatidylcholine synthesis of organoid cultures was enhanced by preincubation with GCS. CORT, as well as the hormonally inactive 11-DHC, increased the incorporation of [14C]choline into phosphatidylcholine. The effect of the latter was completely inhibited by glycyrrhetinic acid (inhibitor of 11 beta-HSD) indicating that it is caused by a previous conversion of 11-DHC into CORT via 11 beta-HSD. Thirdly, preincubation with GCS also altered 11 beta-HSD activity: dexamethasone or CORT both decreased the oxidative and increased the reductive activity in intact cells, indicating that glucocorticoids increase the rate of their own activation by positive feedback.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1984

Effect of estradiol on nonmalignant human mammary cells in primary culture.

We have studied effects of estradiol on primary cultures of nonmalignant human mammary tissue collected surgically from fibroadenomas or during reduction mammoplasties. After enzymatic digestion, "organoids" made of epithelial cells organized in ductal or alveolar structure were grown in primary cultures (up to 12 days) on different substrata (glass, plastic, collagen-coated plastic, and floating collagen membranes). Transmission and scanning electron microscopy showed that these organoids were responsive to physiological concentrations of estradiol. Condensed chromatin of epithelial cells became dispersed following estrogen treatment. The plasma membrane of epithelial cells at the surface of the organoids was dramatically modified by estradiol, which increased the number and the length of the microvilli, as observed previously in the MCF7 breast cancer cell line (Vic et al., Cancer Res., 42: 667-673, 1982). This effect was not observed with the same concentrations of progesterone, dexamethasone, dihydrotestosterone, or 1 microM tamoxifen or in fibroblasts of the same tissue, demonstrating that epithelial mammary cells are specifically responsive to estradiol. By contrast, no effect of estradiol could be evidenced on the [35S]methionine-labeled proteins released into the medium by the organoids. The estrogen-regulated protein of Mr 52,000 was not found in the medium after purification by concanavalin A-sepharose or immunoprecipitation with specific antibodies to the Mr 52,000 protein from MCF7 cells. We conclude that nonmalignant mammary cells are responsive to estrogens in primary culture.

Adenofibroma↗
PubMed1980

[Ultrastructure of skeletal muscle tissue of microwave damaged chick embryos].

The effect of ultrahigh-frequency energy of electromagnetic field of low intensity on certain morphometric indices of intracellular organoids and on cellular ultrastructure were studied in the developing skeletal muscular tissue of chick embryos. In the skeletal muscles of irradiated embryos a limited cellular destruction, structural disorders in myonic organoids were revealed. Reactive-recovery processes manifested themselves in hyperplasy and hypertrophy of organoids, in activation of protein synthesis, in increasing amount of myosatellites. At early stages after irradiation peripheral mitochondria are subjected to greater changes. After hatching, central mitochondria in myons suffer more. Quantitative changes in myonic organoids and degree of their destruction seem to depend on.a peculiar differentiation of the muscular tissue, blood supply and innervation of the muscle as an organ.

Age Factors↗
PubMedDate not supplied

[The differentiation of tumor cells of the human large intestine during the acquisition of multiple drug resistance].

By selection in the medium containing increasing actinomycin D concentrations two sublines with acquired multidrug resistance (MDR) caused by P-glycoprotein (P170) overproduction were isolated. The obtained cell lines as well as parent cells grow in vitro as morphologically organized aggregates, so-called organoids. Comparative electron microscopic study of sensitive and drug resistant organoids has shown that the development of MDR was accompanied by the enhancement of the tumour cell differentiation: the percentage of differentiated cells, the extent of their maturity, and the quantity of lumens were higher in MDR organoids than in parent cell line. The size of glandular structures in resistant organoids was also enlarged. Possible mechanisms of observed phenomenon are discussed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

PMC42, a novel model for the differentiated human breast.

Cultured human breast carcinoma cell lines are important models for investigating the pathogenesis of breast cancer. Their use, however, is limited because of loss of expression of breast-specific markers and the development of a dedifferentiated phenotype after continuous culture. PMC42 is a unique human breast carcinoma line, previously shown to express secretory and myoepithelial markers. We have induced PMC42 cells to form hollow organoids in culture, similar to in vivo breast structures, using a combination of hormones including estrogen, progesterone, dexamethasone, insulin, and prolactin in combination with a permeable extracellular matrix. The organoids comprised polarized cells located around a central lumen. Expression of beta-casein was demonstrated in cells within organoids using reverse transcriptase-polymerase chain reaction, Western blot analysis, and confocal immunofluorescence. In this in vitro system, milk-specific gene expression was induced through hormone and matrix interactions which may be similar to those operating in vivo. PMC42 is a novel model for investigations into the molecular mechanisms of carcinogenesis and differentiation in the human breast.

Blotting, Western↗
PubMed2026

Metabolic atlas of early human cortex reveals glycolytic remodeling and pentose phosphate pathway control of cell fate transitions.

Cortical development involves rapid progenitor expansion and cell diversification supported by tightly regulated metabolic programs, yet these programs remain largely uncharacterized in human development. Here, we generated a metabolic atlas of the early human cortex using primary tissue and stem cell-derived cortical organoids. We observed dynamic changes in core metabolic functions, including an unexpected increase in glycolysis and pentose phosphate pathway (PPP) activity during late neurogenesis. Manipulation of glucose availability in cortical organoids altered cell-type composition, increasing outer radial glia (oRG) and inhibitory neuron populations. Pharmacological and genetic inhibition of PPP enzymes recapitulated these cell fate changes. Ribose was sufficient to rescue radial glia (RG) gene expression changes, revert organoid cell-type composition, and restore levels of ATP and hypotaurine. These data identify a critical role for the PPP in modulating RG cell fate specification and generate a resource for future exploration of additional metabolic pathways in human cortical development.

cell fate↗
PubMed2025

Liquid Biopsy-Multiomics Link Adhesion Pathway Dysregulation to Kidney Injury Severity.

INTRODUCTION: Severe acute kidney injury (AKI) is strongly associated with the risk of developing chronic kidney disease; however, little is known about the cell type-specific mechanisms driving kidney injury severity. METHODS: In this multicenter observational study, we used clinically obtained liquid biopsy proteomics and machine learning (ML) to predict severe outcomes in patients with COVID-associated and non-COVID AKI. Further, we orthogonally combined 169 urine proteomics with 437 plasma proteomics samples and 40 urine sediment single-cell transcriptomics samples to identify complementary dysregulated mechanisms. RESULTS: Using a 10-fold cross-validated random forest algorithm, we identified a set of urinary proteins that demonstrate predictive power for both discovery and validation set with AUC of 87% and 76%, respectively. These predictive proteomics features obtained demonstrate that cell adhesion and autophagy-associated pathways are uniquely impacted in severe AKI. Differentially abundant proteins (DAPSs) associated with these pathways are highly expressed in cells of the juxtamedullary nephron, endothelial cells (ECs), and podocytes, indicating that these kidney cell types could be potential targets. Single-cell transcriptomic analysis in the in vitro model of kidney organoids infected with SARS-CoV-2 reveal dysregulation of extracellular matrix (ECM) organization in multiple nephron segments, recapitulating the clinically observed fibrotic response across multiomics datasets. Ligand-receptor interaction analysis of the podocyte and tubule organoid clusters shows significant reduction and loss of interaction between integrins and basement membrane receptors in the infected kidney organoids. CONCLUSION: Collectively, these data suggest that ECM degradation and adhesion-associated mechanisms could be the main driver of severe kidney injury.

AKI↗
PubMed2025

Single-cell analysis of dup15q syndrome reveals developmental and postnatal molecular changes in autism.

Duplication 15q (dup15q) syndrome is a leading genetic cause of autism spectrum disorder, offering a key model for studying autism-related mechanisms. Using single-cell and single-nucleus RNA sequencing of cortical organoids from dup15q patient-derived iPSCs and post-mortem brain samples, we identify increased glycolysis, disrupted layer-specific marker expression, and aberrant morphology in deep-layer neurons during fetal-stage organoid development. In adolescent-adult postmortem brains, upper-layer neurons exhibit heightened transcriptional burden related to synaptic signaling, a pattern shared with idiopathic autism. Using spatial transcriptomics, we confirm these cell-type-specific disruptions in brain tissue. By gene co-expression network analysis, we reveal disease-associated modules that are well preserved between postmortem and organoid samples, suggesting metabolic dysregulation that may lead to altered neuron projection, synaptic dysfunction, and neuron hyperexcitability in dup15q syndrome.

Humans↗
PubMedDate not supplied

Initial assessment of a tissue engineered stomach derived from syngeneic donors in a rat model.

The objective of this study is to assess the feasibility of creating a tissue engineered stomach using isolated stomach epithelium organoid unit from syngeneic adult donors and a biodegradable polymer scaffold in a rat model. Despite recent advances in reconstruction techniques, total gastrectomy is still accompanied by various complications. As an alternative treatment, a tissue engineered stomach that replaces the mechanical and metabolic functions of a normal stomach is proposed. Stomach epithelium organoid units were isolated from syngeneic adult rats and seeded onto biodegradable polymers. These constructs were implanted into the omenta of recipient adult rats. All constructs were harvested for histologic and immunohistochemical examination at designated time points. Cyst-like structures were formed that showed the development of vascularized tissue with a neomucosa. Immunohistochemical staining for alpha-actin smooth muscle, gastric mucin, and proton pump indicated the presence of a smooth muscle layer and gastric epithelium, as well as the existence of parietal cells of the stomach mucosa, respectively. Epithelium derived stomach organoid units seeded on biodegradable polymers were transplanted in donor rats and have been shown to vascularize, survive, and regenerate into complex tissue resembling a native stomach. These initial results are encouraging, and studies are currently underway to further assess this approach.

Absorbable Implants↗
PubMed2025

EGFR activation in cholangiocytes promotes extrahepatic bile duct regeneration after injury.

BACKGROUND: The EGF receptor family of 4 tyrosine kinases, EGFR and ERBB2-4, and their ligands regulate the development and homeostasis of digestive organs including the hepatobiliary system. It promotes intrahepatic cholangiocyte proliferation, bile duct development, and cholangiocarcinoma aggressiveness. The EGF signaling network's contribution to extrahepatic bile duct (EHBD), which is a distinct hepatobiliary entity, regeneration is poorly defined. This work aimed to determine the fundamental role of the EGF signaling network in the biliary proliferative response to EHBD obstruction. METHODS: We used mouse bile duct ligation to model obstructive EHBD injury, and human and mouse EHBD organoids for in vitro studies. We tested activating and inhibitory paradigms with recombinant EGF family ligands and receptor antagonists. Transcriptomic and immunohistochemistry analyses informed EGF signaling changes and cellular localization at homeostasis and after obstruction. RESULTS: At homeostasis, the EHBD expressed EGFR ligands Tgfa, Btc, Hbegf, and Nrg4 in cholangiocytes, and Egf and Nrg2 in stromal cells. Erbb2 and Erbb3 were predominant receptors expressed in cholangiocytes, and Egfr in stromal cells at baseline. Post-injury, biliary hyperproliferation was associated with increased abundance of Tgfa, Btc, Hbegf, and Areg ligands and Egfr receptor in cholangiocytes with resulting EGFR activation. EGFR ligands induced biliary organoid growth, and inhibition of EGFR, not ERBB2, dampened organoid proliferation. EGFR inhibition in mice led to a decrease in the biliary proliferative response after EHBD obstruction. CONCLUSIONS: The obstruction-induced biliary proliferation is EGFR-mediated, suggesting context-specific and receptor-specific EGF signaling network contribution to EHBD regeneration after injury.

Animals↗
PubMed2023

Unraveling Neuronal Identities Using SIMS: A Deep Learning Label Transfer Tool for Single-Cell RNA Sequencing Analysis.

Large single-cell RNA datasets have contributed to unprecedented biological insight. Often, these take the form of cell atlases and serve as a reference for automating cell labeling of newly sequenced samples. Yet, classification algorithms have lacked the capacity to accurately annotate cells, particularly in complex datasets. Here we present SIMS (Scalable, Interpretable Machine Learning for Single-Cell), an end-to-end data-efficient machine learning pipeline for discrete classification of single-cell data that can be applied to new datasets with minimal coding. We benchmarked SIMS against common single-cell label transfer tools and demonstrated that it performs as well or better than state of the art algorithms. We then use SIMS to classify cells in one of the most complex tissues: the brain. We show that SIMS classifies cells of the adult cerebral cortex and hippocampus at a remarkably high accuracy. This accuracy is maintained in trans-sample label transfers of the adult human cerebral cortex. We then apply SIMS to classify cells in the developing brain and demonstrate a high level of accuracy at predicting neuronal subtypes, even in periods of fate refinement, shedding light on genetic changes affecting specific cell types across development. Finally, we apply SIMS to single cell datasets of cortical organoids to predict cell identities and unveil genetic variations between cell lines. SIMS identifies cell-line differences and misannotated cell lineages in human cortical organoids derived from different pluripotent stem cell lines. When cell types are obscured by stress signals, label transfer from primary tissue improves the accuracy of cortical organoid annotations, serving as a reliable ground truth. Altogether, we show that SIMS is a versatile and robust tool for cell-type classification from single-cell datasets.

Brain organoids↗
PubMed2026

The molecular similarity landscape of preclinical cancer models to patient tumors.

Selecting appropriate preclinical models is fundamental for translational oncology, yet a large-scale, multi-omic quantitative comparison of their similarity to primary human tumors is lacking. To address this, we integrated transcriptomic, proteomic, and genomic profiles from over 10,000 primary tumors from The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC), alongside 4,000 preclinical models. Using a robust computational framework, we revealed a clear hierarchy of transcriptomic and proteomic similarity to patient tumors: with patient-dervied xenografts (PDXs) having greater transcriptomic and proteomic similarity to patient tumors (>) compared with patient-derived organoids (PDOs), which are equal in hierarchy to that of PDX-dervied organoids (PDXOs) > cell lines. We also quantified high molecular conservation (Pearson correlation coefficient = 0.96) across paired in vitro to in vivo platform (organoids to PDX) transitions. Furthermore, genomic analysis demonstrated that whole-exome sequencing (WES) outperforms RNA-seq in detecting DNA variants, and it identified a clonal complexity hierarchy (cell lines > PDXOs > PDXs > PDOs) reflecting the effect of passaging history on intratumor heterogeneity. Ultimately, this study delivers a comprehensive quantitative benchmark, establishing a population-level hierarchy of molecular similarity between preclinical models and primary tumors and providing a data-driven reference for model selection. These findings offer a data-driven framework for selecting models that balance biological representativeness with experimental practicality.

Humans↗
PubMed1992

A functional model of adult human prostate epithelium. The role of androgens and stroma in architectural organisation and the maintenance of differentiated secretory function.

A functional model of adult human prostate epithelium is described. This model shows that stromal cells, but not an androgenic stimuli, are required for architectural organisation of prostate epithelium. Within an organised structure, androgenic stimulation is required for the establishment of secretory epithelial cell morphology and associated function. In the absence of stromal cells but in the presence of androgens architectural organisation and secretory function are lost. Epithelial parenchymal units (organoids) from human prostate tissue were isolated, cultured within a three-dimensional collagen matrix, and xenografted subcutaneously into athymic mouse hosts. The grafted gels were rapidly invaded by host fibroblasts. Epithelial organisation initially disappeared but was re-established concurrently with the stromal cell invasion. In intact male hosts, cuboidal and columnar cells that expressed human prostate-specific secretory markers were found. In castrated male and in female hosts epithelial structures were lined with flattened epithelium with no secretory function. This phenomenon could be reversibly replicated by treating intact male hosts with the anti-androgen Flutamide. Gels containing organoids grafted within 0.45 microns Millipore chambers were not invaded by stromal cells and rapidly lost all epithelial organisation and secretory function. When organoids cocultured with human foreskin fibroblasts were grafted within chambers, structural organisation of the epithelium was supported. These results indicate that both heterologous human fibroblasts and mouse stromal cells are capable of permissively supporting adult human prostate epithelial function.

Aged↗
PubMed2006

A pilot study investigating a novel subcutaneously implanted pre-cellularised scaffold for tissue engineering of intestinal mucosa.

Tissue engineering of the small intestine offers an alternative to long-term intravenous nutrition and transplantation in patients with intestinal failure. Initial work, although encouraging, is limited by the volume of neonatal tissue required to produce a small neomucosal cyst. Our novel approach is to implant tubular poly-lactide-co-glycolide (PGLA) foam scaffolds subcutaneously. The aim of this study was to investigate whether these scaffolds would support growth of intestinal neomucosa. PGLA scaffolds were implanted subcutaneously into 8 Lewis rats; after 5 weeks, 'organoid units' were injected into the lumens. Tissue was assessed histologically after harvesting and quantitative immunohistochemistry was performed using antibodies against vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGF-R2), fibroblast growth factor basic (bFGF) and fibroblast growth factor receptor 2 (FGF-R2). At 4 weeks post organoid unit implantation, clearly recognisable mucosa and submucosa was present on the luminal surface of the scaffold. Densities of VEGF and VEGF-R2 positive cells increased with time post organoid unit implantation. This pilot study demonstrates that it is possible to tissue engineer small intestinal neomucosa using subcutaneously implanted PLGA scaffolds. The yield of the process compares favourably to the published literature. Further work is required to optimise the technique.

Animals↗