First-generation stem cells are comprised of unselected cell mixtures exemplified by unfractionated bone-marrow-derived mononuclear stem cells
Initial stem-cell trials have established safety and feasibility, but show limited efficacy in the context of cardiovascular disease
The main hurdles to achieving benefit from stem-cell therapy include poorly defined cell populations, quality control in cell processing, and limited efficiency in cell delivery
To improve the regenerative effect, investigators have focused on purified cell populations to eliminate nonregenerative cells
Next-generation cell therapy ushers a new era in regenerative medicine by targeting organ or disease before implantation
The interplay between the diseased heart and regenerative biotherapeutics is critical in achieving repair
The global impetus to identify curative therapies has been fuelled by the unmet needs of patients in the context of a growing heart failure pandemic. To date, regeneration trials in patients with cardiovascular disease have used stem-cell-based therapy in the period immediately after myocardial injury, in an attempt to halt progression towards ischaemic cardiomyopathy, or in the setting of congestive heart failure, to target the disease process and prevent organ decompensation. Worldwide, several thousand patients have now been treated using autologous cell-based therapy; the safety and feasibility of this approach has been established, pitfalls have been identified, and optimization procedures envisioned. Furthermore, the initiation of phase III trials to further validate the therapeutic value of cell-based regenerative medicine and address the barriers to successful clinical implementation has led to resurgence in the enthusiasm for such treatments among patients and health-care providers. In particular, poor definition of cell types used, diversity in cell-handling procedures, and functional variability intrinsic to autologously-derived cells have been identified as the main factors limiting adoption of cell-based therapies. In this Review, we summarize the experience obtained from trials of 'first-generation' cell-based therapy, and emphasize the advances in the purification and lineage specification of stem cells that have enabled the development of 'next-generation' stem-cell-based therapies targeting cardiovascular disease.
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Behfar, A., Crespo-Diaz, R., Terzic, A. et al. Cell therapy for cardiac repair—lessons from clinical trials. Nat Rev Cardiol 11, 232–246 (2014). https://doi.org/10.1038/nrcardio.2014.9
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