Stem Cell Differentiation/Undifferentiation Stabilizing Reagent for High Quality Manufacturing

Botulinum non-toxic hemagglutinin(bHA) fragment controls E-cadherin cell-cell adhesion

Features

  • Maintains undifferentiation of iPS/ES cells in 2D/3D culture.
  • Removes differentiated iP/ES cells in 2D culture.
  • Stabilizes ectoderm/mesoderm/endoderm and downstream differentiations.
  • Demonstrated cardiomyocytes, pancreatic cells, lung cells, hepatocyte, RPE differentiations.

Background and Technology

Regenerative medicine led by academia utilizing iPSC/ESC technologies have been reported for many indications. Those are realized by semi-manual cell culturing by skilled technicians. However, for wide-spread use of regenerative medicine by iPSC/ESC derived cells, establishment of low cost, high quality and largescale cell production protocol is crucial.
A team of The University of Osaka, who has been tackling this issue, found that controlling cell junction force can ease the stress to the cells, maintain quality(undifferentiation), and guide differentiation by adding bHA at the biggening of standard differentiation protocols. bHA can be synthesized in E-coli expression system.

Patents

Filed by Osaka University:

WO2014/104207, WO2015/199243, WO2018/117110, WO2023/149565, WO2023/149566.

Publications

Suman Chandra Nath, Tomohiro Tokura, Mee-Hae Kim, and Masahiro Kino-oka: “Botulinum Hemagglutinin–Mediated in Situ Break–up of Human Induced Pluripotent Stem Cell Aggregates for High–Density Suspension Culture”, Biotechnol. Bioeng., Vol. 115, No. 4, pp. 910-920 (2018). (doi:10.1002/bit.26526)

Mee-Hae Kim, Naruchit Thanuthanakhun, and Masahiro Kino-oka: “Novel Strategy to Improve Hepatocyte Differentiation Stability through Synchronized Behavior-Driven Mechanical Memory of iPSCs”, Biotechnol. Bioeng., Vol.120, No.2, 593-607 (2023). (doi: 10.1002/bit.28285)

Mee-Hae Kim, Naruchit Thanuthanakhun, and Masahiro Kino-oka: “A Simple Tool for The Synchronous Differentiation of Human Induced Pluripotent Stem Cells into Pancreatic Progenitors”, Biotechnol. J., Vol.19, 2300364 (2024). (doi:10.1002/biot.202300364)

Riku Yamamoto, Ryo Sakakibara, Mee-Hae Kim, Yukako Fujinaga, and Masahiro Kino-oka: “Growth Prolongation of Human Induced Pluripotent Stem Cell Aggregate in Three-Dimensional Suspension Culture System by Addition of Botulinum Hemagglutinin”, J. Biosci. Bioeng., Vol.137, No.2, pp.141-148 (2024). (doi: 10.1016/j.jbiosc.2023.11.010)

Researcher

Professor, Masahiro Kino-oka, Department of Biotechnology, The University of Osaka

Expectations

  • We are seeking companies who license and commercialize this technology.
  • Cell therapy companies, CDMOs, reagent manufactures are welcome.
  • Samples can be provided under MTA.

 

Project.KJ-00179

 

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