{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T13:47:52Z","timestamp":1785764872039,"version":"3.56.0"},"reference-count":38,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Although the thymus and parathyroid glands originate from the third pharyngeal pouch, their postnatal relationship has been predominantly interpreted in embryological terms, with limited structural evidence supporting a functional interaction. The aim of this study was to explore whether multimodal observations support a previously underrecognized structural relationship between the thymus and parathyroid glands. For this purpose, microCT-based three-dimensional reconstruction was used to assess their spatial and branching high-attenuation structures, and the findings were correlated with histomorphometric analysis, immunohistochemical evaluation of vascular and extracellular matrix markers, scanning electron microscopy (SEM), and available clinical data. MicroCT analysis revealed distinct three-dimensional architectural patterns in thymic and parathyroid tissues. Histomorphometric and immunohistochemical findings revealed stromal organization and molecular expression patterns compatible with tissue remodeling. SEM provided additional microarchitectural detail, supporting the presence of structural continuity. Notably, the integration of three-dimensional imaging with histological and ultrastructural data revealed a previously underrecognized level of organization at the parathyroid\u2013thymus interface. The overall findings indicate a more complex organized anatomical and microvascular relationship rather than a simple juxtaposition of two distinct structures. Taken together, these multimodal findings support the hypothesis of a previously underexplored structural relationship between the thymus and parathyroid glands. However, the proposed microarchitectural framework should be considered exploratory and requires validation using dedicated vascular imaging and morphometric techniques. The observed micro-tissue-specific architecture suggests that an organized structure may facilitate inter-structural communication, potentially resembling a port system-like arrangement. Further studies are required to clarify its physiological relevance.<\/jats:p>","DOI":"10.3390\/ijms27156926","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T12:57:56Z","timestamp":1785761876000},"page":"6926","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Multimodal Morphological and Immunohistochemical Analysis of the Human Thymus\u2013Parathyroid Relationship"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4760-0200","authenticated-orcid":false,"given":"Maria-Paula","family":"Comanescu","sequence":"first","affiliation":[{"name":"Department of Surgery I, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, University Street No. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delia","family":"H\u00eenganu","sequence":"additional","affiliation":[{"name":"Department of Morpho-Functional Sciences I, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, University Street No. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius Valeriu","family":"H\u00eenganu","sequence":"additional","affiliation":[{"name":"Department of Morpho-Functional Sciences I, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, University Street No. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otilia","family":"Boi\u0219teanu","sequence":"additional","affiliation":[{"name":"Department of Surgery I, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, University Street No. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3994-6579","authenticated-orcid":false,"given":"Ludmila","family":"Lozneanu","sequence":"additional","affiliation":[{"name":"Department of Morpho-Functional Sciences I, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, University Street No. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6872-8616","authenticated-orcid":false,"given":"Fabian Cezar","family":"Lupu","sequence":"additional","affiliation":[{"name":"Department of Mechanical, Mechatronics and Robotics Engineering, Mechanical Engineering Faculty, \u201cGheorghe Asachi\u201d Technical University of Iasi, 700050 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiberiu","family":"Lunguleac","sequence":"additional","affiliation":[{"name":"Department of Surgery I, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, University Street No. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Salahoru","sequence":"additional","affiliation":[{"name":"Department of Surgery I, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, University Street No. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana","family":"Grigorovici","sequence":"additional","affiliation":[{"name":"PhD Program in Medicine, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, University Street No. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandru","family":"Grigorovici","sequence":"additional","affiliation":[{"name":"Department of Surgery I, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, University Street No. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1053\/j.semdp.2021.06.003","article-title":"The thymus: Embryology, anatomy and histology","volume":"39","author":"Perez","year":"2022","journal-title":"Semin. Diagn. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Salahoru, P., Grigorescu, C., Hinganu, M.V., Lunguleac, T., Halip, A.I., and Hinganu, D. (2024). Thymus Surgery Prospectives and Perspectives in Myasthenia Gravis. J. Pers. Med., 14.","DOI":"10.3390\/jpm14030241"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1038\/s43587-024-00801-1","article-title":"Paracrine FGF21 regulates thymic epithelial cell homeostasis","volume":"5","author":"Wedemeyer","year":"2025","journal-title":"Nat. Aging"},{"key":"ref_4","first-page":"203","article-title":"Thymic involution and immune aging","volume":"23","author":"Lynch","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e2250202","DOI":"10.1002\/eji.202250202","article-title":"T-cell selection in the thymus: New routes toward the identification of the self-peptide ligandome presented by thymic epithelial cells","volume":"53","author":"Sousa","year":"2023","journal-title":"Eur. J. Immunol."},{"key":"ref_6","first-page":"247","article-title":"Thymic stromal cell heterogeneity","volume":"22","author":"Cosway","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_7","first-page":"45","article-title":"Thymus organogenesis and function","volume":"23","author":"Rodewald","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"ref_8","first-page":"133","article-title":"Thymus organization and selection","volume":"21","author":"Anderson","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Wang, H., and Z\u00fa\u00f1iga-Pfl\u00fccker, J.C. (2022). Thymic microenvironment: Interactions between innate immune cells and developing thymocytes. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.885280"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1007\/s11357-022-00720-2","article-title":"The aging of the immune system and its implications for transplantation","volume":"45","author":"McGovern","year":"2023","journal-title":"GeroScience"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Comanescu, M.P., Boi\u0219teanu, O., H\u00eenganu, D., H\u00eenganu, M.V., Grigorovici, R., and Grigorovici, A. (2025). Perspectives on the parathyroid\u2013thymus interconnection. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26136000"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Comanescu, M.P., Boi\u0219teanu, O., H\u00eenganu, D., Lozneanu, L., Lupu, F.C., Grigorovici, R., Grigorovici, A., Lunguleac, T., and H\u00eenganu, M.V. (2025). Cross-expression of thymic and parathyroid hormone receptors. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262311561"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"H\u00eenganu, M.V., Cucu, R.P., Costan, V.V., Lozneanu, L., Tamas, C., Calistru, A.E., Hristian, L., and H\u00eenganu, D. (2024). Aging of Superficial Musculoaponeurotic System of the Face-Novel Biomarkers and Micro-CT Relevance of Facial Anti-Gravity Support. Diagnostics, 14.","DOI":"10.3390\/diagnostics14111126"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Stucker, S., De Angelis, J., and Kusumbe, A.P. (2021). Heterogeneity and dynamics of vasculature in the endocrine system. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.624928"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4833","DOI":"10.1016\/j.cell.2024.07.012","article-title":"A systems view of the vascular endothelium in health and disease","volume":"187","author":"Augustin","year":"2024","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1910811","DOI":"10.1002\/adfm.201910811","article-title":"From arteries to capillaries: Approaches to engineering human vasculature","volume":"30","author":"Fleischer","year":"2020","journal-title":"Adv. Funct. Mater."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/nrm2639","article-title":"Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system","volume":"10","author":"Augustin","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"426","DOI":"10.7150\/thno.34126","article-title":"Type H blood vessels in bone modeling and remodeling","volume":"10","author":"Peng","year":"2020","journal-title":"Theranostics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"110887","DOI":"10.1016\/j.exger.2020.110887","article-title":"T cells, aging and senescence","volume":"134","author":"Pangrazzi","year":"2020","journal-title":"Exp. Gerontol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Shichkin, V.P., Felli, M.P., Screpanti, I., and Antica, M. (2022). Editorial: Thymus function and aging: A focus on thymic epithelial cells. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1003490"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.cytogfr.2025.08.001","article-title":"Neuro-endocrine-immune regulation of metabolic homeostasis","volume":"85","author":"Xie","year":"2025","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.3382\/ps.0731049","article-title":"Neuroendocrine-immune interactions","volume":"73","author":"Marsh","year":"1994","journal-title":"Poult. Sci."},{"key":"ref_23","unstructured":"Khan, M., Jose, A., and Sharma, S. (2026, June 03). Physiology, parathyroid hormone, StatPearls, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK499940\/."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"685","DOI":"10.37358\/RC.19.2.6985","article-title":"Particularities of using contrast agents in diagnosis of stroke","volume":"70","author":"Cuciureanu","year":"2019","journal-title":"Rev. Chim."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4","DOI":"10.21037\/gs-2025-aw-516","article-title":"Beyond bones and stones: The relationship between hyperparathyroidism and diabetes","volume":"15","author":"Caretti","year":"2026","journal-title":"Gland Surg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1038\/nrendo.2015.139","article-title":"PTH receptor-1 signalling\u2014Mechanistic insights and therapeutic prospects","volume":"11","author":"Cheloha","year":"2015","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"031914","DOI":"10.1117\/1.NPh.9.3.031914","article-title":"Immune\u2013vascular mural cell interactions","volume":"9","author":"Barkaway","year":"2022","journal-title":"Neurophotonics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2174\/1877609401305010001","article-title":"An update on the structure of the parathyroid gland","volume":"5","author":"Chen","year":"2013","journal-title":"Open Anat. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"100282","DOI":"10.1016\/j.jvssci.2025.100282","article-title":"Changes in vascular identity during vascular remodeling","volume":"6","author":"Aoyagi","year":"2025","journal-title":"JVS Vasc. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e51413","DOI":"10.7554\/eLife.51413","article-title":"Endothelial heterogeneity across distinct vascular beds during homeostasis and inflammation","volume":"9","author":"Jambusaria","year":"2020","journal-title":"eLife"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Gifre-Renom, L., Daems, M., Luttun, A., and Jones, E.A.V. (2022). Organ-specific endothelial cell differentiation and impact of microenvironmental cues on endothelial heterogeneity. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031477"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e68578","DOI":"10.7554\/eLife.68578","article-title":"Structural insights into the activation of human calcium-sensing receptor","volume":"10","author":"Chen","year":"2021","journal-title":"eLife"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1002\/jbmr.4682","article-title":"Management of primary hyperparathyroidism","volume":"37","author":"Bilezikian","year":"2022","journal-title":"J. Bone Miner. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1146\/annurev-cellbio-112122-023316","article-title":"Thymic mimetic cells: Ontogeny as immunology","volume":"40","author":"Michelson","year":"2024","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Le, N.T. (2023). Metabolic regulation of endothelial senescence. Front. Cardiovasc. Med., 10.","DOI":"10.3389\/fcvm.2023.1232681"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/nature17040","article-title":"Angiocrine functions of organ-specific endothelial cells","volume":"529","author":"Rafii","year":"2016","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/nrm2183","article-title":"Molecular regulation of angiogenesis and lymphangiogenesis","volume":"8","author":"Adams","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1146\/annurev.cellbio.21.012704.131525","article-title":"Stem cell niche: Structure and function","volume":"21","author":"Li","year":"2005","journal-title":"Annu. Rev. Cell Dev. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6926\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T13:07:05Z","timestamp":1785762425000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6926"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,1]]},"references-count":38,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27156926"],"URL":"https:\/\/doi.org\/10.3390\/ijms27156926","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,1]]}}}