Encapsulated Pheochromocytoma Cells Secrete Potent Noncatecholamine Factors
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Mobine-2009-Encapsulated Pheochr.pdf
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Author(s)
Mobine, Hector R.
Engelmayr, George C.
Moussazadeh, Nelson
Anwar, Tayyba R.
Freed, Lisa E.
Edelman, Elazer R.
Date Issued
July 2009
Journal
Tissue Engineering. Part A
Publisher
Mary Ann Liebert, Inc.
Citation
Mobine, Hector R. et al. “Encapsulated Pheochromocytoma Cells Secrete Potent Noncatecholamine Factors.” Tissue Engineering Part A 15.7 (2011) : 1719-1728. © Mary Ann Liebert, Inc.
Version
Final published version
Abstract
Pheochromocytomas are widely believed to induce cardiomyopathy via hypersecretion of catecholamines, including norepinephrine (NE). NE can have direct cardiomyocyte toxicity and/or can stimulate myocardial remodeling secondary to the induction of hypertension. Yet, the development of cardiomyopathy is not entirely related to catecholamine dose or the extent of hypertension. To explore these effects, we engineered a polymeric encapsulation system to control PC12 cell kinetics and NE release in vitro and in vivo. Primary neonatal rat cardiomyocytes incubated with pheochromocytoma-conditioned media exhibited greater cytoskeletal changes than myocytes cultured with identical doses of NE alone, including more profound dose-dependent decreases in desmin, [beta]-tubulin, and vinculin and upregulation of dystrophin. Cardiomyocyte contractility was 29 ± 6% greater at given levels of NE release. Agarose-encapsulated PC12 cells retain cell viability and structural integrity in vivo. These implants induce a 30% greater degree of cardiac enlargement as compared to pumps releasing equivalent doses of NE. Protein level alterations observed in vitro were mirrored in vivo after implantation of encapsulated cells or NE pumps for 28 days. Together, these data suggest that pheochromocytoma-induced cardiomyopathy is not solely a catecholamine-mediated event; rather, the pathogenesis of this dilated cardiomyopathy appears to be dependent upon secondary factors unexamined to date.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1089/ten.tea.2008.0412
