Examples of Pediatric Tissues/Organs Used in Specific Disease Research Studies

Tissue/OrganInvestigational TechniqueDisease or Process InvestigatedMolecules and/or Parameters Investigated
BrainWestern blot,112,113 IHC,53,111114 IF, FISH,53 FACS,53,114 transmission electron microscopy,113 lipid content analysis, gene expression analysis,112 RT-PCR,112,114 cell culture,53,114 ICC, confocal microscopy, generation of lentiviral-based Gli binding site-RFP reporters and cell transfection,114 Proton density-weighted MRI scan,110 light and electron microscopy111• Adrenoleukodystrophy112• VLC fatty acid, cholesterol ester, cholesterol, sphingomyelin, cytokines (IL-1α, IL-2, IL-3, IL-6, TNF-α, and GM-CSF), chemokines (CCL2, -4, -7, -11, -16, -21, -22, CXCL1, CX3CL1, and SDF2) and iNOS112
• Diffuse intrinsic pontine gliomas114• Hh signaling pathway114
• Infantile neuronal ceroid lipofuscinosis113• PPT1, caspase-3, cleaved-PARP, caspase-9, ROS, and SOD-2113
• Infiltrative glioma and gliosis53• EGFR53
• Autism197199• Neuronal microexons,197 molecular networks,198 microRNAs199
• Acute myelogenous leukemia or medulloblastoma111• DCX, CD20, CD68, Ki67, CD3111
Heart/vesselsLight and electron microscopy,167,200 fatty acid analysis by gas chromatography,200 PCR,137 histopathologic examination, IHC, confocal microscopy,35 general histochemistry (H&E, Weigert’s fuchsin-resorcin)168• Infantile X-linked dilated cardiomyopathy200• Saturated fatty acids, mitochondria structure200
• Dilated cardiomyopathy and congenital heart disease137• Levels of HHV-6137
• Chagas disease35• Quilty effect, rejection, C myocarditis reactivation, fibrosis, hypertrophy, and ischemia; as well as lymphocytic cellular infiltration of myocarditis35
• Cardiovascular development167,168• Morphology and mechanical properties of the atrial intima167
• Normal histologic growth of ascending aorta, aortic isthmus, and descending aorta168
MuscleGeneral histochemistry (H&E, Gomori trichrome, detection of ragged-red fibers and nemaline rods, oil red detection of lipids, and periodic acid-Schiff detection of glycogen), electron microscopy, IHC37; Histologic examination42• Neuromuscular disorders (including muscular dystrophy, neurogenic atrophy, and congenital and metabolic disorders)37• Ultrastructural pathology of mitochondria, general and enzyme histochemistry and IHC of the muscle37
• Musculoskeletal lesions (bone and soft tissue) in children42• Test the accuracy and safety of image-guided PCNB for the detection of benign or malignant lesions42
LungMicrobiologic analysis, bacteria and fungi analysis103,104• Respiratory diseases103• Morphology/anatomy of the lungs; levels of aerobic and anaerobic microorganisms; and fungi103
• Sudden unexpected death in infancy104• Postmortem translocation (the migration of bacteria from mucosal surfaces into the body after death, which occurs as part of the normal putrefaction process) and the association with PMI104
SpleenCT scan,201 histologic evaluation (H&E)57,201• Splenic epidermoid cysts201• Examination of the wall of the cyst for ultimate diagnosis201
• Fetal malformations57• Comparison of needle autopsy specimens and complete conventional autopsy specimens57
Pancreas, pancreatic islets, bile ductDNA sequencing, chip assays, cell culture and transfections136• Type 2 diabetes and other islet disorders136• Epigenomic profile of unstimulated human pancreatic islets, including DNase I hypersensitive sites that mark regions of open chromatin, loci enriched for active histone H3 lysine methylation modifications (H3K4me1, H3K4me3, and H3K79me2), and binding sites for the insulator CTCF136
• Type 2 diabetes106• Multiple TCF7L2 splicing forms106
5′ RACE and analysis of splicing forms, RT-PCR106 IHC, western blot40• Pancreaticobiliary maljunction and bile duct dilatation40• P-MLC20 and MLCK pathway40
LiverGenotyping, QuantiGene Plex 2.0 assay (Affymetrix Ltd, High Wycombe, UK)119; Q-FISH telomere quantification method160• Hyperbilirubinemia and prediction of UGT1A1-mediated drug metabolism and toxicity119• Genetic polymorphisms on UGT1A1 transcription; enhanced transcription by CAR, PXR, GR, HNF1α, and HNF4α237
• Pediatric living donor160• Telomere length160
IntestineRT-PCR202• Oral drug absorption and hepatic drug excretion202• Hepatic and intestinal drug transporters MRP2, OATP1B1, OATP1B3, OATP2B1, and MDR1202
StomachHistologic evaluation (H&E, and Giemsa staining),13 C-UBT, RUT, fqPCR122• Gastritis122• Levels of Helicobacter pylori122
CorneaGraft failure62a• Endothelial disease62• Success rate of penetrating keratoplasty and corneal graft survival62b
Retina, posterior poleHPLC70; IHC71• Macular degeneration70• CoQ10 levels70
• Retinopathy and choroidopathy71• Choroidal endothelial Tbdn and choroid vascular Tbdn71
LensIHC, slit lamp biomicroscopy, tryptic digest tandem mass spectrometry protein sequencing, Aβ fluoro-ELISA and Aβ immunoblotting, light and electron microscopy, immunogold electron microscopy89• Down syndrome and Alzheimer’s disease89• Aβ accumulation, amyloid formation, and fiber cell cytoplasmic Aβ aggregates89
KidneyDoppler ultrasonography, histopathologic diagnosis203; IHC39; Histologic evaluation (H&E)57• Kidney disease203• Comparison of outpatient and inpatient renal biopsies: accuracy, safety, and risks of complications203
• Pediatric solid tumors39• HA117, P-gp39
• Fetal malformations57• Limitations of needle autopsies from a complete conventional autopsy57
BladderHistologic evaluation (H&E, and Masson’s trichrome staining), ultrasonography150• Bladder plate polyposis150• Examination of novel technique of SUPER and UAAC. Evaluation on polyp recurrence, bladder tumor, urinary continence, and social dryness150
Lymph nodesNode weight, ultrasound, pathologic examination204• Acquired immune defi ciency syndrome204• CD4+ T-cell2 count and HIV viral load, fecal calprotectin, and bowel ultrasound, with the latter evaluating bowel wall thickness and mesenteric lymph nodes204
Bone marrowPCR, PCR-RFLP, histologic evaluation (Giemsa staining), bone marrow culture205• Visceral leishmaniasis205• Leishmania DNA205
SkinHistologic evaluation (H&E), immunoperoxidase206• Primary cutaneous plasmacytosis206• Search for cell infiltration of dermis, clusters of B-lymphocytes CD20 reactive, and expression of κ light chains and λ light chains to diagnosis rare disease206
PlacentaPlacental weights, pathologic examination (thrombosis present, leukocytes infiltration, infarction)95• Stillbirth95• Placental abnormalities including thrombosis present, placental infarction, leukocyte infiltration, and chorioamnionitis95
MeDIP, human CpG island plus promoter microarray analysis, bisulfite sequencing PCR188• Preeclampsia188• Aberrant or altered patterns of DNA methylation and the distribution of CpG nucleotides in genes such as CAPN2, EPHX2, ADORA2B, SOX7, CXCL1, and CDX1188
Umbilical cord bloodGeneration of iPSCs, transfection, RT-PCR, IF flow cytometry73• Acquired immune defi ciency syndrome73• Anti-HIV genes including a CCR5 short hairpin RNA and human/rhesus chimeric TRIM5α gene; also, pluripotency markers OCT4, SOX2, NANOG, and SSEA473
HPLC and detection by an API 2000 (American Petroleum Institute [API], Washington, DC) electrospray triple quadrupole mass spectrometer, a gel permeation chromatography column for lipid content analysis189• Exposure to endocrine disruptors during pregnancy and infancy189• Levels of non-POPs (including MEHP, OP, and 4-NP), and PBDEs189
Fetal tissues: Kidney, Heart, Liver, Muscle, Brain, Skin, PancreasLocked nucleic acid probe-Southern, CpG methylation analysis85• Congenital myotonic dystrophy type 185• Expanded CTG repeat and methylation at the CTCF-binding sites85
• Polycystic kidney disease86• Structural proteins vinculin, α-actinin, and β1-integrin; focal adhesion proteins including FAK, c-Src, paxillin, and p130cas; and fibrocystin-186
Cell adhesion assays, migration assays, western blots, IHC86c; MRI,172,173 ultrasound172• Prenatal ventriculomegaly172• Images to compare postmortem examination, both by traditional neuropathologic examination and postmortem MRI, with antenatal MRI for diagnosis172
• Major pathologic lesions associated with death173• Images to compare minimally invasive autopsy (a postmortem investigation with no incisions or dissection, with MRI and postmortem blood sampling via needle puncture) with conventional autopsy for detection of cause of death173
  • ADORA2B, adenosine A2B receptor; CAPN2, calpain-2 catalytic subunit 2; CAR, androstane receptor; CCL, chemokine (C-C motif) ligand; CD3, cluster of differentiation 3; CD4, cluster of differentiation 4; CD20, cluster of differentiation 20; CD68, cluster of differentiation 68; CoQ10, coenzyme Q10; CpG, C–phosphate–G (cytosine nucleotide sites); 13C-UBT, 13C-urea breath test; c-Src, Proto-oncogene tyrosine-protein kinase Src; CTCF, CCCTC-binding factor; CXCL1, the chemokine (C-X-C motif) ligand 1; DCX, doublecortin; EGFR, epidermal growth factor receptor; EPHX2, epoxide hydrolase 2; FACS, fluorescence-activated cell sorting; FAK, focal adhesion kinase; FISH, fluorescence in situ hybridization; fqPCR, fluorescent quantitative PCR; Gli-RFP reporter, Gli luciferase reporter; GM-CSF, granulocyte-macrophage colony-stimulating factor; GR, glucocorticoid receptor; ICC, immunocytochemistry; IF, immunofluorescence; IHC, immunohistochemistry; IL, interleukin; iNOS, inducible nitric oxide synthase; HA117, a novel multidrug resistance gene; H&E, hematoxylin and eosin; Hh, Hedgehog; HHV-6, human herpesvirus 6; HIV-1, HIV type 1; HNF1α, hepatocyte nuclear factor 1α; HNF4α, hepatocyte nuclear factor 4α; HPLC, high-performance liquid chromatography; iPSCs, induced pluripotent stem cells; Ki67, antigen identified by monoclonal antibody; MDR1, multidrug resistance 1; MeDIP, methylated DNA immunoprecipitation; MEHP, mono-2-ethylhexylphthalate; MLCK, myosin light-chain kinase; MRP2, multidrug resistance protein 2; NANOG, homeobox protein NANOG; non-POPs, non–persistent organic pollutants; 4-NP, 4-nonylphenol; OATP1B1, organic anion transporting polypeptide 1B1; OATP1B3, organic anion transporting polypeptide 1B3; OATP2B1, organic anion transporting polypeptide 2B1; OCT4, octamer-binding transcription factor 4; OP, octylphenol; p130Cas, Crk-associated substrate; PARP, poly (ADP-ribose) polymerase; PBDEs, polybrominated diphenyl ethers; PCNB, percutaneous core needle biopsy; P-gp, permeability glycoprotein; P-MLC20, phosphorylated myosin regulatory light chain; PPT1, palmitoyl protein thioesterase-1; PXR, pregnane X receptor; Q-FISH, quantitative fluorescence in situ hybridization; ROS, reactive oxygen species; SDF2, stromal cell–derived factor 2; SOD-2, superoxide dismutase-2; SOX2, sex determining region Y-box 2; SOX7, SRY-related HMG-box 7; SSEA4, stage-specific embryonic antigen-4; SUPER, sub-urothelial polyp enucleation resection; RT-PCR, reverse transcription PCR; RUT, rapid urease test; Tbdn, Tubedown; TCF7L2, transcription factor 7-like 2; TNF, tumor necrosis factor; UAAC, urothelial auto-augmentation cystoplasty; UGT1A1, UDP-glucuronosyltransferase 1A1; VLC, very long chain fatty acids.

  • a Defined as regraft or, in the absence of regraft, a cloudy cornea in which there was loss of central graft clarity sufficient to compromise vision for a minimum of 3 consecutive months.

  • b CD4+ T cells refer to cells that express the surface protein CD4.

  • c For kidney tissue only.