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Sensing the Cardiac Environment: Exploiting Cues for Regeneration

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Abstract

Recent pre-clinical and clinical studies indicate that certain exogenous stem cells and biomaterials can preserve cardiac tissue after myocardial infarction. Regarding stem cells, a growing body of data suggests that the short-term positive outcomes are mainly attributed to paracrine signaling mechanisms. The release of such factors is due to the cell’s ability to sense cardiac environmentally derived cues, though the exact feedback loops are still poorly understood. However, given the limited engraftment and survival of transplanted cells in the ischemic environment, the long-term clinical benefits of these therapies have not yet been realized. To overcome this, the long-term controlled delivery of bioactive factors using biomaterials is a promising approach. A major challenge has been the ability to develop timely and spatially controlled gradients of different cues, pivotal for the development and regeneration of tissues. In addition, given the complexity of the remodeling process after myocardial infarction, multiple factors may be required at distinct disease stages to maximize therapeutic outcomes. Therefore, novel smart materials that can sense the surrounding environment and generate cues through on demand mechanisms will be of major importance in the translation of these promising advanced therapies. This article reviews how the cardiac environment can mediate the release profiles of bioactive cues from cells and biomaterials and how the controlled delivery impacts heart regeneration.

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Acknowledgments

This work was supported in part by a Marie Curie-Reintegration Grant (FP7-People-2007-4-3-IRG; contract no. 230929), the MIT-Portugal program, the Portuguese Foundation for Science and Technology (FCT; PTDC/SA-BEB/098468/2008; PTDC/CTM/099659/2008) and Crioestaminal (project no. CENTRO-01-0202-FEDER-005476 “INJECTCORD”) to LF. This work was also supported by the National Institute of Health grants DE019191, HL095722, and HL097172 to JMK. The authors would also like to thank FCT for the fellowship to MNP (SFRH/BD/43013/2008).

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  1. Center of Neurosciences and Cell Biology (CNC), University of Coimbra, 3004-417, Coimbra, Portugal

    Maria José Nunes Pereira & Lino S. Ferreira

  2. Biocant- Center of Biotechnology Innovation Center, 3060-197, Cantanhede, Portugal

    Isabel Fidalgo Carvalho & Lino S. Ferreira

  3. Center for Regenerative Therapeutics and Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Harvard-MIT Division of Health Sciences and Technology, 65 Landsdowne Street, Cambridge, MA, 02139, USA

    Maria José Nunes Pereira & Jeffrey M. Karp

  4. Harvard Stem Cell Institute, Harvard University, 1350 Massachusetts Avenue, Cambridge, MA, 02138, USA

    Maria José Nunes Pereira & Jeffrey M. Karp

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  1. Maria José Nunes Pereira
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Correspondence to Jeffrey M. Karp or Lino S. Ferreira.

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Pereira, M.J.N., Carvalho, I.F., Karp, J.M. et al. Sensing the Cardiac Environment: Exploiting Cues for Regeneration. J. of Cardiovasc. Trans. Res. 4, 616–630 (2011). https://doi.org/10.1007/s12265-011-9299-6

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