A roadmap for clinical-grade manufacturing of hiPSC: standardized methodologies for reprogramming, expansion, characterization, and biobanking of hiPSC

There is a critical global need for tissue for transplantation in patients with organ failure or degenerative diseases, which often have limited or no treatment options. Cell therapy using human induced pluripotent stem cells (hiPSC) represents a promising alternative to restore lost cellular functions. However, while patient-specific hiPSC lines ensure immunological compatibility, their production under GMP conditions is time-consuming and expensive. A more efficient approach involves creating a bank of allogeneic hiPSC lines from healthy donors with homozygous HLA haplotypes compatible with a large portion of the population. This strategy enables the development of off-the-shelf cell therapy products, reducing time and costs, and avoiding duplication of efforts. Consensus must be reached among professionals with expertise in hiPSC generation and characterization, as well as in large-scale production. Collaboration among these experts would facilitate the optimization and standardization of protocols to obtain high-quality hiPSC lines. The COST Action HAPLO-iPS aims to establish a collaborative network to generate such lines, standardize protocols, and implement a data system to support their use in clinical trials. Here, we describe the work carried out by WG2 (iPSC production) focused on optimizing and standardizing protocols for the generation, characterization, and large-scale expansion of hiPSCs as intermediate materials for the development of cell-based therapies.