Selection for CD26

Background

Cell therapy of diabetes aims at restoring the physiological control of blood glucose by transplantation of functional pancreatic islet cells. A potentially unlimited source of cells for such transplantations would be islet cells derived from an

Methods

Functional Cell-Capture Screening (FCCS) was used to identify markers that preferentially capture the cells expressing both insulin and Nkx6.1, from hESC-derived ILC cells. In order to test whether selection for such markers could improve cell therapy in diabetic mouse models, we used ILC produced from a clinical-grade line of hESC by a refined differentiation protocol adapted to up-scalable bioreactors. Re-aggregated MACS sorted cells were encapsulated in microspheres made of alginate modified to reduce foreign body reaction. Implantation was done intraperitoneally in STZ-treated C57BL/6 immuno-competent mice.

Results

CD49A (integrin alpha1) was identified by FCCS as a marker for cells that express insulin (or C-peptide) as well as Nkx6.1 in ILC derived by hESC differentiation. The ILC fraction enriched in CD49A

Conclusions

Refining the composition of ILC differentiated from hPSC by negative selection to remove cells expressing CD26 and positive selection for CD49A expressing cells could enable more effective cell therapy of diabetes.

Informations de copyright

Copyright © 2021 Molakandov, Berti, Beck, Elhanani, Walker, Soen, Yavriyants, Zimerman, Volman, Toledo, Erukhimovich, Levy, Hasson, Itskovitz-Eldor, Chebath and Revel.

Déclaration de conflit d'intérêts

KM, DB, AB, KY, MZ, IT, AE, AL, AH, JI-E, and JC are researchers employed in the Biotechnology Company Kadimastem Ltd., Nes Ziona, Israel. MR is a major shareholder of Kadimastem. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.