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Turbulence Activates Platelet Biogenesis to Enable Clinical Scale Ex Vivo Production
Open accessAbstract
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.
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Cites
HDAC6 is a microtubule-associated deacetylase
Hubbert, C., Guardiola, A., Shao, R., Kawaguchi, Y., Ito, A., Nixon, A., Yoshida, M., Wang, X.-F., & Yao, T.-P. (2002) · Nature · doi:10.1038/417455a · Cited by 2,403 · cited 3×
“On the other hand, our data suggest intracellular NRDC directly binds to tubulins (a4A-tubulin or b1-tubulin) (Figure 6C) and perhaps plays a role in tubulin conformation and remodeling by coordinating with HDAC6 (Figures 6E and 6F) (Hubbert et al., 2002; Miyake et al., 2016).”
Interpretation of Shotgun Proteomic Data
Nesvizhskii, A. I., & Aebersold, R. (2005) · Molecular & Cellular Proteomics · doi:10.1074/mcp.r500012-mcp200 · Cited by 1,025
Structural insights into HDAC6 tubulin deacetylation and its selective inhibition
Miyake, Y., Keusch, J. J., Wang, L., Saito, M., Hess, D., Wang, X., Melancon, B. J., Helquist, P., Gut, H., & Matthias, P. (2016) · Nature Chemical Biology · doi:10.1038/nchembio.2140 · Cited by 315
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“Extracellular IGFBP2 andMIF promote the release of extracellular matrix (ECM) for cell clustering to support proplatelet elongation.”
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Metadata
- Authors
- Ito, Y., Nakamura, S., Sugimoto, N., Shigemori, T., Kato, Y., Ohno, M., Sakuma, S., Ito, K., Kumon, H., Hirose, H., Okamoto, H., Nogawa, M., Iwasaki, M., Kihara, S., Fujio, K., Matsumoto, T., Higashi, N., Hashimoto, K., Sawaguchi, A., Harimoto, K.-I., Nakagawa, M., Yamamoto, T., Handa, M., Watanabe, N., Nishi, E., Arai, F., Nishimura, S., & Eto, K.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 174
- Issue
- 3
- Pages
- 636-648.e18
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2883086294
- Cited by
- 296
- References
- 4
- FWCI
- 23.25
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Ito, Y., Nakamura, S., Sugimoto, N., Shigemori, T., Kato, Y., Ohno, M., Sakuma, S., Ito, K., Kumon, H., Hirose, H., Okamoto, H., Nogawa, M., Iwasaki, M., Kihara, S., Fujio, K., Matsumoto, T., Higashi, N., Hashimoto, K., Sawaguchi, A., . . . Eto, K. (2018). Turbulence Activates Platelet Biogenesis to Enable Clinical Scale Ex Vivo Production. Cell. https://doi.org/10.1016/j.cell.2018.06.011
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
