{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T10:33:00Z","timestamp":1794047580134,"version":"4.8.0"},"reference-count":0,"publisher":"Ferrata Storti Foundation (Haematologica)","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["haematol"],"abstract":"<jats:p>Inherited platelet disorders (IPD) comprise a clinically and genetically heterogeneous group of conditions affecting platelet number, function, or both. Although next-generation sequencing has accelerated gene discovery, it has also produced a growing number of variants of uncertain significance, creating a pressing need for experimental systems that can establish causal genotype\u2013phenotype relationships. Because megakaryocytes are scarce in the bone marrow and murine models incompletely recapitulate human platelet biology, human cell-based models are indispensable for studying megakaryopoiesis and platelet formation. Here we review the evolution of such models and their application to IPD research. Leukemia-derived megakaryocytic cell lines provided the first genetically tractable models but incompletely reproduce physiological thrombopoiesis. Megakaryocytes derived from primary hematopoietic stem cells remain the gold standard for patient-specific disease modeling, offering high biological relevance but requiring donor material and being subject to significant inter-donor variability. Induced pluripotent stem cells provide a renewable source of megakaryocytes for disease modeling, although efficient platelet production and functional characterization remain challenging. In contrast, the immortalized megakaryocyte cell line offers a scalable and genetically tractable platform that faithfully recapitulates megakaryocyte maturation, supports platelet production, and enables selected platelet function assays. We further discuss emerging three-dimensional and organoid systems that begin to capture the complexity of the bone-marrow niche. Across these platforms we discuss applications in disease mechanism discovery, functional validation of novel variants, and preclinical evaluation of therapies. No single model is universally optimal; rather, model choice should be guided by the biological question, with validation against primary patient material remaining essential.<\/jats:p>","DOI":"10.3324\/haematol.2026.301744","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:24:22Z","timestamp":1792653862000},"source":"Crossref","is-referenced-by-count":0,"title":["Human cell models for inherited platelet disorders: strengths, limitations and emerging technologies"],"prefix":"10.3324","author":[{"given":"Kato","family":"Ramaekers","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Freson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1856","published-online":{"date-parts":[[2026,10,22]]},"container-title":["Haematologica"],"original-title":[],"link":[{"URL":"https:\/\/haematologica.org\/article\/download\/14500\/81033","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/haematologica.org\/article\/download\/14500\/81033","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T10:15:51Z","timestamp":1794046551000},"score":1,"resource":{"primary":{"URL":"https:\/\/haematologica.org\/article\/view\/14500"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,22]]},"references-count":0,"URL":"https:\/\/doi.org\/10.3324\/haematol.2026.301744","relation":{},"ISSN":["1592-8721","0390-6078"],"issn-type":[{"value":"1592-8721","type":"electronic"},{"value":"0390-6078","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10,22]]}}}