Bone morphogenetic protein-2-independent bone formation by human iPSC-derived megakaryocytes and platelets
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.
Authors
- Michiaki Mukai (ORCID: https://orcid.org/0000-0002-4673-4734)
- Bahityar Rahmutulla (ORCID: https://orcid.org/0000-0002-4014-2789)
- Seiji Ohtori (ORCID: https://orcid.org/0000-0001-5738-6184)
- Sou Nakamura (ORCID: https://orcid.org/0000-0002-5601-9777)
- Ikuko Tajiri (ORCID: https://orcid.org/0000-0002-2627-091X)
- Miyako Suzuki‐Narita (ORCID: https://orcid.org/0000-0001-6427-3807)
- Masaki Fukuyo
- Koji Eto (ORCID: https://orcid.org/0000-0002-5863-7122)
- Sumihisa Orita (ORCID: https://orcid.org/0000-0003-2676-5469)
- Norichika Mizuki (ORCID: https://orcid.org/0000-0003-0207-4233)
- Si Jing Chen (ORCID: https://orcid.org/0000-0002-7857-1140)
- Susumu Tashiro (ORCID: https://orcid.org/0009-0006-8126-1289)
- Kazuhide Inage (ORCID: https://orcid.org/0000-0003-0540-4613)
- Kentaro Kosaka (ORCID: https://orcid.org/0009-0002-6858-9870)
- Sudip Kumar Paul (ORCID: https://orcid.org/0009-0000-3131-0042)
- Takahito Arai
- Yasuhiro Shiga (ORCID: https://orcid.org/0000-0003-4887-0008)
- Yawara Eguchi (ORCID: https://orcid.org/0000-0003-2247-5376)
- Atsushi Kaneda (ORCID: https://orcid.org/0000-0002-6980-5515)
- Masashi Sato (ORCID: https://orcid.org/0000-0001-5294-9232)
- Naoya Takayama (ORCID: https://orcid.org/0000-0001-6867-1677)
Institutions
- Chiba University (JP)
- Kyoto University (JP)
- Teikyo University Chiba Medical Center (JP)
Publication Details
- Journal
- Bone
- Published
- 2025-11-05
- DOI
- https://doi.org/10.1016/j.bone.2025.117703
- Primary Topic
- Periodontal Regeneration and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00