{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T08:04:49Z","timestamp":1774771489832,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["CC2027toDB."],"award-info":[{"award-number":["CC2027toDB."]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["CC2027toDB"],"award-info":[{"award-number":["CC2027toDB"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HemaSphere"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Myeloproliferative Neoplasms (MPN) are malignancies of hematopoietic stem and progenitor cells (HSPCs) that lead to the overproduction of mature blood cells. These disorders include Essential Thrombocythemia (ET), Polycythemia Vera (PV), and Primary Myelofibrosis (PMF), primarily driven by somatic mutations such as\n                    <jats:italic>JAK2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>V617F<\/jats:italic>\n                    <\/jats:sup>\n                    . Research indicates that mesenchymal stromal cells (MSCs) support fibrosis in PMF, though their role in ET and PV remains less clear. Furthermore, in vivo studies of ET\/PV HSPCs remain a challenge due to low engraftment levels in xenograft models. We employed a 3D scaffold model to create an MPN humanized xenograft mouse model, enabling in vivo functional studies of primary MPN progenitor cells and the supportive role of human MSCs. Using this model, we first demonstrated robust hematopoietic support of healthy (HD) HSPCs by PV and ET MSCs. We then investigated the role of MSCs in sustaining\n                    <jats:italic>JAK2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>V617F<\/jats:italic>\n                    <\/jats:sup>\n                    mutant cells by using a CRISPR\u2010Cas9 editing model, along with primary PV and ET HSPCs. Our results showed consistent engraftment of CRISPR\u2010edited\n                    <jats:italic>JAK2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>V617F<\/jats:italic>\n                    <\/jats:sup>\n                    mutant HSPCs and PV and ET patient\u2010derived HSPCs in scaffolds seeded with HD, PV, and ET stroma, providing the first in vivo evidence that PV and ET MSCs can sustain both healthy and MPN\u2010associated hematopoiesis. Furthermore, HD MSCs were also capable of sustaining PV and ET HSPCs in vivo. Overall, we present the first humanized MPN xenograft model that offers valuable insights into how human BM MSCs interact with\n                    <jats:italic>JAK2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>V617F<\/jats:italic>\n                    <\/jats:sup>\n                    mutant clones.\n                  <\/jats:p>","DOI":"10.1002\/hem3.70185","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T08:50:51Z","timestamp":1755852651000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mesenchymal stromal cells from\n                    <i>JAK2<\/i>\n                    <sup>\n                      <i>V617F<\/i>\n                    <\/sup>\n                    myeloproliferative neoplasms support healthy and malignant hematopoiesis in a humanized scaffold model in vivo"],"prefix":"10.1002","volume":"9","author":[{"given":"Alessandra","family":"Ferrelli","sequence":"first","affiliation":[{"name":"Haematopoietic Stem Cell Laboratory The Francis Crick Institute London UK"},{"name":"School of Cancer and Pharmaceutical Sciences King's College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syed","family":"Mian","sequence":"additional","affiliation":[{"name":"Haematopoietic Stem Cell Laboratory The Francis Crick Institute London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marion","family":"Piganeau","sequence":"additional","affiliation":[{"name":"Haematopoietic Stem Cell Laboratory The Francis Crick Institute London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hector","family":"Huerga Encabo","sequence":"additional","affiliation":[{"name":"Haematopoietic Stem Cell Laboratory The Francis Crick Institute London 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