Turbulence Activates Platelet Biogenesis to Enable Clinical Scale Ex Vivo Production.
Abstrak
The ex vivo generation of platelets from human-induced pluripotent cells (hiPSCs) is expected to compensate donor-dependent transfusion systems. However, manufacturing the clinically required number of platelets remains unachieved due to the low platelet release from hiPSC-derived megakaryocytes (hiPSC-MKs). Here, we report turbulence as a physical regulator in thrombopoiesis in vivo and its application to turbulence-controllable bioreactors. The identification of turbulent energy as a determinant parameter allowed scale-up to 8 L for the generation of 100 billion-order platelets from hiPSC-MKs, which satisfies clinical requirements. Turbulent flow promoted the release from megakaryocytes of IGFBP2, MIF, and Nardilysin to facilitate platelet shedding. hiPSC-platelets showed properties of bona fide human platelets, including circulation and hemostasis capacities upon transfusion in two animal models. This study provides a concept in which a coordinated physico-chemical mechanism promotes platelet biogenesis and an innovative strategy for ex vivo platelet manufacturing.
Penulis (28)
Yukitaka Ito
Sou Nakamura
N. Sugimoto
Tomohiro Shigemori
Yoshikazu Kato
Mikiko Ohno
S. Sakuma
Keitaro Ito
H. Kumon
Hidenori Hirose
Haruki Okamoto
M. Nogawa
Mio Iwasaki
Shunsuke Kihara
K. Fujio
Takuya Matsumoto
N. Higashi
K. Hashimoto
A. Sawaguchi
Kenichi Harimoto
M. Nakagawa
Takuya Yamamoto
M. Handa
N. Watanabe
E. Nishi
F. Arai
S. Nishimura
K. Eto
Akses Cepat
- Tahun Terbit
- 2018
- Bahasa
- en
- Total Sitasi
- 245×
- Sumber Database
- Semantic Scholar
- DOI
- 10.1016/j.cell.2018.06.011
- Akses
- Open Access ✓