Regenerative Therapy (Jun 2024)

Osteogenic effects and safety of human induced pluripotent stem cell-derived megakaryocytes and platelets produced on a clinical scale

  • Takahito Arai,
  • Yasuhiro Shiga,
  • Michiaki Mukai,
  • Naoya Takayama,
  • Susumu Tashiro,
  • Ikuko Tajiri,
  • Kentaro Kosaka,
  • Masashi Sato,
  • Sou Nakamura,
  • Haruki Okamoto,
  • Seiji Kimura,
  • Kazuhide Inage,
  • Miyako Suzuki-Narita,
  • Yawara Eguchi,
  • Sumihisa Orita,
  • Koji Eto,
  • Seiji Ohtori

Journal volume & issue
Vol. 26
pp. 850 – 858

Abstract

Read online

Introduction: Platelet-rich plasma obtained by centrifuging peripheral blood can promote osteogenesis owing to its abundant growth factors but has drawbacks, including rapid growth factor loss and inconsistent effects depending on donor factors. To overcome these issues, we were the first in the world to use freeze-dried human induced pluripotent stem cell-derived megakaryocytes and platelets (S-FD-iMPs) and found that they have osteogenesis-promoting effects. Since turbulence was found to activate platelet biogenesis and iPS cell-derived platelets can now be produced on a clinical scale by a device called VerMES, this study examined the osteogenesis-promoting effect and safety of clinical-scale FD-iMP (V-FD-iMPs) for future human clinical application. Method: We administered either S-FD-iMPs, V-FD-iMPs, or saline along with artificial bone to the lumbar spine of 8-week-old male Sprague–Dawley rats (n = 4 each) and evaluated bone formation by computed tomography (CT) and pathology. Next, we administered V-FD-iMPs or saline along with artificial bone to the lumber spines of 5-week-old male New Zealand White rabbits (n = 4 each) and evaluated the bone formation by CT and pathology. Rats (n = 10) and rabbits (n = 6) that received artificial bone and V-FD-iMPs in the lumbar spine were also observed for 6 months for adverse events, including infection, tumor formation, and death. Results: Both V-FD-iMPs and S-FD-iMPs significantly enhanced osteogenesis in the lumber spines of rats in comparison with the controls 8 weeks postoperatively, with no significant differences between them. Furthermore, V-FD-iMPs vigorously promoted osteogenesis in the lumber spines of rabbits 8 weeks postoperatively. In rats and rabbits, V-FD-iMPs showed no adverse effects, including infection, tumor formation, and death, over 6 months. Conclusion: These results suggest that V-FD-iMPs promote safe osteogenesis.

Keywords