Entering the Industrial iPSC Era
As we take the next steps in induced pluripotent stem cell technology, we are faced with enormous challenges
Behnam Ahmadian Baghbaderani | | Opinion
Shinya Yamanaka’s groundbreaking invention of reprogramming human somatic cells into induced pluripotent stem cells (iPSC) has not only impacted the field of drug discovery, toxicity testing and in-a-dish disease modeling, but also profoundly revolutionized the field of cell and gene therapy. The capacity of iPSCs to expand in vitro andthen differentiate into specialized cells (which is to say, directed differentiation into any cell type in the body) as per user needs makes iPSCs a promising and unlimited cell source for curative clinical cell replacement therapies and disease modeling. The advance has led to a growing demand for high quality tissue and pluripotent stem cell-based therapeutics.
Over the last decade, several clinical trials using iPSC-derived specialized cells have been planned, including: mesenchymal stem cells for the treatment of steroid-resistant acute graft versus host disease/GvHD; dopaminergic progenitors for the treatment of Parkinson’s disease; natural killercell-based cancer immunotherapy for the treatment of advanced solid tumors; retinal pigment epithelial cells for the treatment of age-related macular degeneration (AMD); insulin secreting beta cells for the treatment of type I diabetes; and human iPSC-based cancer immunotherapy.
Despite the advances in the iPSC field, major challenges remain in terms of industrializing iPSC-based therapies – specifically, relating to reprogramming and directed differentiation. Reprogramming somatic cells into iPSCs to generate a master cell bank (MCB) is a highly manual and open process, requiring specialized skills and, therefore, continuous training. The expansion process from a vial of banked iPSCs to generate large numbers of iPSCs has been the focus of recent work, leading to closed automated processing that can support industrialization (1, 2). Following expansion, directed differentiation of cells to the target cell type remains highly variable, however. A prime reason for this is that directed differentiation requires very careful optimization of the differentiation factors, their concentrations, and timing of their addition – all of which vary depending on the target cell type and the protocol used by different investigators (3). Current processes for directed differentiation for the generation of iPSC-derived cell therapy products are also not robust and reproducible, and tend to rely on highly manual, open manipulation steps. Moreover, some of the critical materials used in the process may lack qualified or reliable manufacturers/vendors – and some are only available as research-use only reagents.
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