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Translational aspects of cardiac cell therapy.

Chen CH, Sereti KI, Wu BM, Ardehali R - J. Cell. Mol. Med. (2015)

Bottom Line: Cell therapy has been intensely studied for over a decade as a potential treatment for ischaemic heart disease.An alternative strategy involving either direct reprogramming of endogenous cardiac fibroblasts or stimulation of resident cardiomyocytes to regenerate new myocytes can potentially overcome the limitations of exogenous cell delivery.Complimentary approaches utilizing combination cell therapy and bioengineering techniques may be necessary to provide the proper milieu for clinically significant regeneration.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

No MeSH data available.


Related in: MedlinePlus

A combined approach for amelioration of injury and rejuvenation of cardiac tissue. Successful cardiac regeneration will likely necessitate a combination of therapeutic approaches. (A) Delivery of exogenous cells has been demonstrated via epicardial, intramyocardial (endocardial), intracoronary and intravenous routes. (B) Fibroblasts directly reprogrammed into cardiomyocytes either in vitro or in vivo can potentially serve as an abundant source of cells for cardiac regeneration. (C) Stimulation of native cardiomyocyte proliferation may be possible using a number of protein- and nucleic acid- based factors. Delivery of multiple cell types (E) along with delivery of biomaterials-based scaffolding (D) may be necessary for optimal cell engraftment and tissue regeneration.
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fig02: A combined approach for amelioration of injury and rejuvenation of cardiac tissue. Successful cardiac regeneration will likely necessitate a combination of therapeutic approaches. (A) Delivery of exogenous cells has been demonstrated via epicardial, intramyocardial (endocardial), intracoronary and intravenous routes. (B) Fibroblasts directly reprogrammed into cardiomyocytes either in vitro or in vivo can potentially serve as an abundant source of cells for cardiac regeneration. (C) Stimulation of native cardiomyocyte proliferation may be possible using a number of protein- and nucleic acid- based factors. Delivery of multiple cell types (E) along with delivery of biomaterials-based scaffolding (D) may be necessary for optimal cell engraftment and tissue regeneration.

Mentions: Despite these advances, significant obstacles remain in the field; low cell survival, poor engraftment and limited functional maturation (of progenitor cells) have blunted potential therapeutic benefit. While from a putative standpoint one would expect cell therapy to exert its beneficial effect by repopulating the damaged myocardium by the exogenous cells, others have argued that the delivery of exogenous cells may lead to recruitment of intrinsic cells capable of regenerating the damaged muscle; hence the loss of transplanted cells after a short time does not preclude the promise of stem cell therapy. Cell therapy strategies involving direct reprogramming of endogenous cardiac fibroblasts into cardiomyocytes and stimulation of endogenous cardiomyocyte expansion through growth and transcription factor delivery have the potential to sidestep the inherent limitations of exogenous cell delivery. Ultimate success with cardiac cell therapy will likely necessitate a combined strategy involving exogenous delivery of multiple complementary cell types, soluble factors for enhanced cell survival, concurrent stimulation of endogenous cardiomyocyte regeneration, recruitment and transdifferentiation of endogenous cardiac fibroblasts into cardiomyocytes through direct reprogramming, and the use of biomaterial scaffolds to provide structural support and biochemical cues during delivery (Figure2).


Translational aspects of cardiac cell therapy.

Chen CH, Sereti KI, Wu BM, Ardehali R - J. Cell. Mol. Med. (2015)

A combined approach for amelioration of injury and rejuvenation of cardiac tissue. Successful cardiac regeneration will likely necessitate a combination of therapeutic approaches. (A) Delivery of exogenous cells has been demonstrated via epicardial, intramyocardial (endocardial), intracoronary and intravenous routes. (B) Fibroblasts directly reprogrammed into cardiomyocytes either in vitro or in vivo can potentially serve as an abundant source of cells for cardiac regeneration. (C) Stimulation of native cardiomyocyte proliferation may be possible using a number of protein- and nucleic acid- based factors. Delivery of multiple cell types (E) along with delivery of biomaterials-based scaffolding (D) may be necessary for optimal cell engraftment and tissue regeneration.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4549027&req=5

fig02: A combined approach for amelioration of injury and rejuvenation of cardiac tissue. Successful cardiac regeneration will likely necessitate a combination of therapeutic approaches. (A) Delivery of exogenous cells has been demonstrated via epicardial, intramyocardial (endocardial), intracoronary and intravenous routes. (B) Fibroblasts directly reprogrammed into cardiomyocytes either in vitro or in vivo can potentially serve as an abundant source of cells for cardiac regeneration. (C) Stimulation of native cardiomyocyte proliferation may be possible using a number of protein- and nucleic acid- based factors. Delivery of multiple cell types (E) along with delivery of biomaterials-based scaffolding (D) may be necessary for optimal cell engraftment and tissue regeneration.
Mentions: Despite these advances, significant obstacles remain in the field; low cell survival, poor engraftment and limited functional maturation (of progenitor cells) have blunted potential therapeutic benefit. While from a putative standpoint one would expect cell therapy to exert its beneficial effect by repopulating the damaged myocardium by the exogenous cells, others have argued that the delivery of exogenous cells may lead to recruitment of intrinsic cells capable of regenerating the damaged muscle; hence the loss of transplanted cells after a short time does not preclude the promise of stem cell therapy. Cell therapy strategies involving direct reprogramming of endogenous cardiac fibroblasts into cardiomyocytes and stimulation of endogenous cardiomyocyte expansion through growth and transcription factor delivery have the potential to sidestep the inherent limitations of exogenous cell delivery. Ultimate success with cardiac cell therapy will likely necessitate a combined strategy involving exogenous delivery of multiple complementary cell types, soluble factors for enhanced cell survival, concurrent stimulation of endogenous cardiomyocyte regeneration, recruitment and transdifferentiation of endogenous cardiac fibroblasts into cardiomyocytes through direct reprogramming, and the use of biomaterial scaffolds to provide structural support and biochemical cues during delivery (Figure2).

Bottom Line: Cell therapy has been intensely studied for over a decade as a potential treatment for ischaemic heart disease.An alternative strategy involving either direct reprogramming of endogenous cardiac fibroblasts or stimulation of resident cardiomyocytes to regenerate new myocytes can potentially overcome the limitations of exogenous cell delivery.Complimentary approaches utilizing combination cell therapy and bioengineering techniques may be necessary to provide the proper milieu for clinically significant regeneration.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

No MeSH data available.


Related in: MedlinePlus