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Division of Cardiovascular Surgery, Toronto General Hospital, 4N-470, 200 Elizabeth St, Toronto, ON, Canada M5G 2C4
(Email: danny.spiegelstein{at}gmail.com; ckim{at}utoronto.ca; terry.yau{at}uhn.on.ca).
The beneficial effects of endothelial progenitor cell (EPC) transplantation in various animal experimental studies have been promising, but have shown limited transferability to human clinical trials. There are a few reports evaluating the reduced number and functional capacity of EPCs due to advanced donor age and other comorbidities [1, 2]. Another major issue of EPCs is the limited number of cells that can be obtained for ex vivo expansion for subsequent autologous cell transplantation.
In the current study, Mieno and colleagues [3] evaluated the prevalence, cell surface markers, and functional capacity of EPCs isolated from cryopreserved mononuclear cells (MNCs). They analyzed the efficacy of cryopreserved EPCs as an approach to increase the number of cells available for transplantation and thus to enhance the efficacy of cell therapy in the failing heart. Mieno and associates [3] showed that ex vivo function of cryopreserved EPCs was generally similar to fresh cells, and that EPC characteristics were preserved after freezing and thawing processes, similar to noncryopreserved cells. The results suggest that cryopreserved EPCs may be able to function similarly to freshly isolated cells. As a caveat, the freezing protocol used in this study resulted in the loss of 46% of MNCs. Development of a less injurious freezing regimen may be necessary to maximize the recovery of MNCs and thus the isolation of EPCs.
Taking this approach further, it may be possible to collect EPCs on multiple occasions for cryopreservation prior to reimplantation of a much larger number of cells on a subsequent occasion. This strategy may increase the efficacy of cell therapy, which can be anticipated to be directly related to the number of cells implanted, and thus to the number that survive over at least the medium term. Having a stock of cryopreserved EPCs available for implantation may also permit more timely administration of cell therapy, prior to irreversible post-infarction remodeling of the left ventricle. Delays in ex vivo expansion of donor cells that are harvested only after the occurrence of the clinical event which provides an indication for cell therapy may well limit its ultimate efficacy. Ideally, MNCs could be harvested prior to development of comorbidities (eg, diabetes and hypercholesterolemia) that limit their efficacy after implantation. Alternatively, the thawed cells may need to be augmented to overcome the detrimental effects of advanced donor age and comorbidities.
The possibilities of this approach are without doubt intriguing. If this strategy is to reach fruition, however, additional studies to evaluate the long-term stability of frozen EPCs will be necessary, and evaluation of the post-implantation effect of these cryopreserved EPCs in a relevant animal model will be crucial.
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