Abstract
Human pluripotent stem cells (hPSCs) have practically unlimited proliferation potential and a capability to differentiate into any cell type in the human body. Since the first derivation in 1998, they have been an attractive source of cells for regenerative medicine. Numerous ethical, technological, and regulatory complications have been hampering hPSC use in clinical applications. Human embryonic stem cells (ESCs), parthenogenetic human ESCs, human nuclear transfer ESCs, and induced pluripotent stem cells are four types of hPSCs that are different in many clinically relevant features such as propensity to epigenetic abnormalities, generation methods, and ability for development of autologous cell lines. Propensity to genetic mutations and tumorigenicity are common features of all pluripotent cells that complicate hPSC-based therapies. Several recent advances in methods of derivation, culturing, and monitoring of hPSCs have addressed many ethical concerns and technological challenges in development of clinical-grade hPSC lines. Generation of banks of such lines may be useful to minimize immune rejection of hPSC-derived allografts. In this review, we discuss different sources of hPSCs available at the moment, various safety risks associated with them, and possible solutions for successful use of hPSCs in the clinic. We also discuss ongoing clinical trials of hPSC-based treatments.
Key words::
- Epigenetic aberrations
- good manufacturing practices
- human embryonic stem cells (hESCs)
- human induced pluripotent stem cells (hiPSCs)
- human nuclear transfer embryonic stem cells (NT-ESCs)
- human pluripotent stem cells (hPSCs)
- immune rejection
- parthenogenetic human embryonic stem cells (phESCs)
- stem cell bank
- tumorigenicity
Acknowledgements
Author contributions: O.S., A.D., and P.V.: manuscript writing, collection and assembly of data; S.R.: conception and design, manuscript writing, collection and assembly of data, final approval of manuscript.
Funding: This work was supported by grants to S.R. from Karolinska Institutets Forskningsstiftelser (2014fobi41924); to O.S. from Karolinska University Hospital; and to A.D. from Russian Science Foundation (RSF), Russian Federation (grant 14-15-00712), and from Foundation for Assistance to Small Innovative Enterprises (FASIE), Russian Federation (project Nr. 24026).
Declaration of interest: S.R. is a shareholder in BioLamina, AB. Other authors report no conflicts of interest.