Human induced pluripotent stem cells in regenerative medicine

Human induced pluripotent (iPS) cells offer a theoretically inexhaustible cell source for the derivation of any cell type and are a promising tool in regenerative medicine. Cells can be derived from the recipients own tissue or from pre-selected HLA-matched donors. Certain disease relevant cell types derived from iPS cells can be cryopreserved, distributed worldwide and made available on demand. These factors taken together indicates iPS cells could potentially revolutionize medicine.

Technological maturation has been fast paced with rapid advances in derivation and culture techniques in the last decade, creating cells of sufficient quality to motivate in human use. The first clinical trials performed with iPS cell derived grafts have so far been conducted without indications of adverse events. Pioneering applications are now being evaluated in humans. Meanwhile, academia and industry alike are taking strides to industrialize cell manufacture in anticipation of commercial applications. Strategies utilizing genome editing are opening up entirely new venues for future applications. However, challenges does not solely lay in developing efficacious cell therapies. Pioneering cell therapy products have so far been exceptionally costly. Finding strategies minimize cost may be as an important as proving efficacy if any novel cell therapies are ever going to benefit society.

Regulations dictating the use of iPS cell derived cell therapies remains unspecific yet demanding and insufficiently harmonized internationally. Efforts are ongoing to coordinate in-between regulatory authorities and more defined criteria for manufacture and regulatory approval is slowly emerging. It has now been little over 10 years since the derivation of the first human iPS cell lines. A decade which has seen many barriers overcome. The upcoming decade is likely to be even more exciting and challenging, as therapies will need, not only to be consistently proven safe, but also efficacious and commercially viable.

List of scientific papers

I. Uhlin, E. Rönnholm, H. Day, K. Kele, M. Tammimies, K. Bölte, S. Falk, A. Derivation of Human iPS Cell Lines from Monozygotic Twins in Defined and Xeno Free Conditions. Stem Cell Research.
https://doi.org/10.1016/j.scr.2016.12.006

II. Uhlin, E. Marin Navarro, A. Rönnholm, H. Day, K. Kele. Falk, A. Integration Free Derivation of Human Induced Pluripotent Stem Cells Using Laminin 521 Matrix. Journal of Visualized Experiments. 2017 Jul 7;(125).
https://doi.org/10.3791/56146

III. Uhlin, E. Kele, M. Rönnholm, H. Day, K. Ulfenborg, H. Anderlid, B. Falk, A. Derivation of a GMP-Compliant Human iPS Cell Line “KICRi001-A” from Dermal Fibroblasts by RNA-Mediated Reprogramming. [Submitted]

IV. Uhlin, E. Kele, M. Winblad, N. Baqué–Vidal, L. Petrus-Reurer, S. Bengtsson, M. Lanner, F. Falk, A. A Strategy for the Creation of a Clinical Grade iPS Cell Bank Covering a Majority of the World Population by CRISPR-Cas9 Genome Editing. [Manuscript]

V. Uhlin, E. Morse, R. Kele, M. Holmberg, L. Xu, L. Moslem, M. Sundström, E. Falk, A. Pre-Clinical Evaluation of Clinically Relevant iPS Cell Derived Neuroepithelial Stem Cells as an Off-the-Shelf Cell Therapy for Spinal Cord Injury. [Manuscript]