Human induced pluripotent stem cells (hiPSC), enveloped in elastin-like recombinamers for cell therapy of type 1 diabetes mellitus (T1D): preliminary data

Pia Montanucci; Teresa Pescara; Alessia Greco; Giuseppe Basta; Riccardo Calafiore

doi:10.3389/fbioe.2023.1046206

Human induced pluripotent stem cells (hiPSC), enveloped in elastin-like recombinamers for cell therapy of type 1 diabetes mellitus (T1D): preliminary data

Front Bioeng Biotechnol. 2023 Apr 25:11:1046206. doi: 10.3389/fbioe.2023.1046206. eCollection 2023.

Authors

Pia Montanucci¹, Teresa Pescara¹, Alessia Greco¹, Giuseppe Basta¹, Riccardo Calafiore¹

Affiliation

¹ Division of Internal Medicine and Endocrine and Metabolic Sciences (MISEM), Laboratory for Endocrine Cell Transplants and Biohybrid Organs, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.

Abstract

Introduction: Therapeutic application and study of type 1 diabetes disease could benefit from the use of functional β islet-like cells derived from human induced pluripotent stem cells (hiPSCs). Considerable efforts have been made to develop increasingly effective hiPSC differentiation protocols, although critical issues related to cost, the percentage of differentiated cells that are obtained, and reproducibility remain open. In addition, transplantation of hiPSC would require immunoprotection within encapsulation devices, to make the construct invisible to the host's immune system and consequently avoid the recipient's general pharmacologic immunosuppression. Methods: For this work, a microencapsulation system based on the use of "human elastin-like recombinamers" (ELRs) was tested to envelop hiPSC. Special attention was devoted to in vitro and in vivo characterization of the hiPSCs upon coating with ERLs. Results and Discussion: We observed that ELRs coating did not interfere with viability and function and other biological properties of differentiated hiPSCs, while in vivo, ELRs seemed to afford immunoprotection to the cell grafts in preliminary in vivo study. The construct ability to correct hyperglycemia in vivo is in actual progress.

Keywords: T1D; cell therapy; elastin-like recombinamers; human induced pluripotent stem cells; insulin.

Grants and funding

This work was supported by European Commission Grant Agreement number 646075 “ELASTISLET: tailored elastin-like recombinamers as advanced systems for cell therapies in diabetes mellitus: a synthetic biology approach towards a bioeffective and immunoisolated biosimilar islet/cell niche.”