Bone · 2025
Bone morphogenetic protein-2-independent bone formation by human iPSC-derived megakaryocytes and platelets.
СтатьяНазвание и аннотация: Перевод в очереди
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Mizuki Norichika, Mukai Michiaki, Shiga Yasuhiro, Takayama Naoya, Nakamura Sou, Kosaka Kentaro, Chen Si Jing, Paul Sudip Kumar, Arai Takahito, Tashiro Susumu, Sato Masashi, Fukuyo Masaki, Rahmutulla Bahityar, Tajiri Ikuko, Inage Kazuhide, Suzuki-Narita Miyako, Eguchi Yawara, Orita Sumihisa, Kaneda Atsushi, Eto Koji, Ohtori Seiji
Аннотация
Bone regeneration (BR) is an ongoing challenge in biomedical research. While recombinant human bone morphogenetic protein-2 (rhBMP-2) is available for clinical use, its side effects remain a concern. Patient-derived platelet-rich plasma has been proposed as an alternative, but its heterogeneity poses a major hurdle to standardization. Here, we evaluated the effectiveness of induced pluripotent stem cell (iPSC)-derived megakaryocytes and platelets (iMPs) and recombinant human bone morphogenetic protein-2 (rhBMP-2) as potential BR therapy in a rat lumbar bone graft model. We implanted artificial bones with iMPs and/or rhBMP-2 and performed computed tomography and histological analysis to assess new bone formation. iMPs and rhBMP-2 showed comparable efficacy in vivo, but rhBMP-2 induced significant inflammation. In vitro, iMPs promoted human bone marrow mesenchymal stem cell (BM-MSC) proliferation and migration, while rhBMP-2 enhanced osteodifferentiation. RNA sequencing revealed cell cycle-related gene upregulation by iMPs. Altogether, these findings suggest iMPs, alone or in combination with rhBMP-2, as a promising BR therapy for enhancing clinical efficacy.