{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T10:45:36Z","timestamp":1788864336290,"version":"build-2803163510"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"28","license":[{"start":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:00:00Z","timestamp":1687910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP22bm1004002"],"award-info":[{"award-number":["JP22bm1004002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP21K16337"],"award-info":[{"award-number":["JP21K16337"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP20H03638"],"award-info":[{"award-number":["JP20H03638"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,7,11]]},"abstract":"<jats:p>\n                    Patients with permanent hypoparathyroidism require lifelong replacement therapy to avoid life-threatening complications, The benefits of conventional treatment are limited, however. Transplanting a functional parathyroid gland (PTG) would yield better results. Parathyroid gland cells generated from pluripotent stem cells in vitro to date cannot mimic the physiological responses to extracellular calcium that are essential for calcium homeostasis. We thus hypothesized that blastocyst complementation (BC) could be a better strategy for generating functional PTG cells and compensating loss of parathyroid function. We here describe generation of fully functional PTGs from mouse embryonic stem cells (mESCs) with single-step BC. Using CRISPR-Cas9 knockout of\n                    <jats:italic>Glial cells missing2<\/jats:italic>\n                    (\n                    <jats:italic>Gcm2<\/jats:italic>\n                    ), we efficiently produced aparathyroid embryos for BC. In these embryos, mESCs differentiated into endocrinologically mature PTGs that rescued\n                    <jats:italic>Gcm2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice from neonatal death. The mESC-derived PTGs responded to extracellular calcium, restoring calcium homeostasis on transplantation into mice surgically rendered hypoparathyroid. We also successfully generated functional interspecies PTGs in\n                    <jats:italic>Gcm2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    rat neonates, an accomplishment with potential for future human PTG therapy using xenogeneic animal BC. Our results demonstrate that BC can produce functional endocrine organs and constitute a concept in treatment of hypoparathyroidism.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2216564120","type":"journal-article","created":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T13:34:21Z","timestamp":1687959261000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":19,"title":["Functional calcium-responsive parathyroid glands generated using single-step blastocyst complementation"],"prefix":"10.1073","volume":"120","author":[{"given":"Mayuko","family":"Kano","sequence":"first","affiliation":[{"name":"Stem Cell Therapy Laboratory, Advanced Research Institute, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo 113-8510, Japan"},{"name":"Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan"},{"name":"Metabolism and Endocrinology, Department of Medicine, St. Marianna University School of Medicine, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7276-4753","authenticated-orcid":false,"given":"Naoaki","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Stem Cell Therapy Laboratory, Advanced Research Institute, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo 113-8510, Japan"},{"name":"Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyuki","family":"Sato","sequence":"additional","affiliation":[{"name":"Stem Cell Therapy Laboratory, Advanced Research Institute, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo 113-8510, Japan"},{"name":"Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaharu","family":"Kimura","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cell Therapy, Institute of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rei","family":"Hirochika","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cell Therapy, Institute of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0877-0735","authenticated-orcid":false,"given":"Yasumasa","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, Faculty of Health Science, Suzuka University of Medical Science, Suzuka, Mie 510-0293, 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Medical College, Tokorozawa, Saitama 359-8513, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Kasai","sequence":"additional","affiliation":[{"name":"Stem Cell Therapy Laboratory, Advanced Research Institute, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo 113-8510, Japan"},{"name":"Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Stem Cell Therapy Laboratory, Advanced Research Institute, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo 113-8510, Japan"},{"name":"Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan"},{"name":"Laboratory of Regenerative Medicine, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo 192-0392, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1924-7639","authenticated-orcid":false,"given":"Hidetaka","family":"Suga","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Masaki","sequence":"additional","affiliation":[{"name":"Stem Cell Therapy Laboratory, Advanced Research Institute, Tokyo Medical 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