FEBS Letters special issue on “Stem cell reprogramming”

Reprogramming is the ability to change the fate of a cell to another fate. Cell fate and differentiation program were long thought to be ineluctable, starting at or even prior to its inception. However, technologies such as somatic cell nuclear transfer (SCNT), induced pluripotent stem cells (iPSCs) and direct cell reprogramming demonstrated that the fate of a terminally differentiated cell can be changed.

The excitement about (stem) cell reprogramming is partly due to the prospective to have an unlimited access to virtually any cell type for therapeutic use. These cells could replace the ones lost due to diseases or injuries, through transplantation or transfusion, directly or after modification (including, but not limited to: gene correction, gene addition or introduction of therapeutic molecules). The use of patient-specific somatic cells derived from their own iPSCs or from HLA-compatible iPSCs would overcome the current disadvantages of organ transplantation, such as graft versus host disease and the need for immunosuppressive treatment, and cell-borne diseases. The possibility to reprogram endogenous cells in vivo (in the body), directly at sites of tissue damage, would solve the problem of finding compatible donor cells, tissues and/or organs. Safe therapeutic use of reprogrammed cells is currently being evaluated in preclinical studies because of the risk of tumor formation (for example due to the use of proto-oncogenes as reprogramming factors, insertional mutagenesis, uncontrolled cell proliferation, presence of residual iPS-like cells).

Beside the therapeutic potential, cell reprogramming also offers the opportunity to screen for effective therapeutic drugs, to generate patient cell-derived models to study disease mechanisms, to perform gene therapy, and to study aging versus rejuvenation (since most aging hallmarks are erased during cell reprogramming).

The Special Issue of FEBS Letters covers important aspects of the basic research performed to generate and reprogram hematopoietic and neural (stem) cells in vitro, to better understand the mechanisms of cell reprogramming and to identify the factors that limit the efficiency of this process. Other aspects are also discussed such as the clinical translation of reprogrammed cells in cell-replacement therapy, the necessity for standardized and reproducible protocols and procedures, the economic feasibility of large-scale facilities for stem-cell production and the necessity of strong partnerships between academia and the biotech/pharmaceutical industry to best couple basic research to the clinic. The future research directions and obstacles ahead are put into perspective as well.