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Cytokine-induced differentiation of multipotent adult progenitor cells into functional smooth muscle cells
Jeffrey J. Ross, … , Robert T. Tranquillo, Catherine M. Verfaillie
Jeffrey J. Ross, … , Robert T. Tranquillo, Catherine M. Verfaillie
Published December 1, 2006
Citation Information: J Clin Invest. 2006;116(12):3139-3149. https://doi.org/10.1172/JCI28184.
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Research Article Article has an altmetric score of 6

Cytokine-induced differentiation of multipotent adult progenitor cells into functional smooth muscle cells

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Abstract

Smooth muscle formation and function are critical in development and postnatal life. Hence, studies aimed at better understanding SMC differentiation are of great importance. Here, we report that multipotent adult progenitor cells (MAPCs) isolated from rat, murine, porcine, and human bone marrow demonstrate the potential to differentiate into cells with an SMC-like phenotype and function. TGF-β1 alone or combined with PDGF-BB in serum-free medium induces a temporally correct expression of transcripts and proteins consistent with smooth muscle development. Furthermore, SMCs derived from MAPCs (MAPC-SMCs) demonstrated functional L-type calcium channels. MAPC-SMCs entrapped in fibrin vascular molds became circumferentially aligned and generated force in response to KCl, the L-type channel opener FPL64176, or the SMC agonists 5-HT and ET-1, and exhibited complete relaxation in response to the Rho-kinase inhibitor Y-27632. Cyclic distention (5% circumferential strain) for 3 weeks increased responses by 2- to 3-fold, consistent with what occurred in neonatal SMCs. These results provide evidence that MAPC-SMCs are phenotypically and functionally similar to neonatal SMCs and that the in vitro MAPC-SMC differentiation system may be an ideal model for the study of SMC development. Moreover, MAPC-SMCs may lend themselves to tissue engineering applications.

Authors

Jeffrey J. Ross, Zhigang Hong, Ben Willenbring, Lepeng Zeng, Brett Isenberg, Eu Han Lee, Morayma Reyes, Susan A. Keirstead, E. Kenneth Weir, Robert T. Tranquillo, Catherine M. Verfaillie

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Figure 3

SMC-specific proteins are expressed in SD-MAPCs differentiated with TGF-β1.

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SMC-specific proteins are expressed in SD-MAPCs differentiated with TGF-...
(A) Temporal characterization of SM22α and α-SMA expression on days 0, 2, 4, and 6 (magnification, ×40). SM22α was detected at low levels on day 0, which increased and localized to stress fibers as early as day 2. α-SMA expression was absent on day 0 and detected by day 4. (B) Colocalization of SM22α (green) and α-SMA (red) further demonstrates that expression of SM22α precedes that of α-SMA. (C) IgG control. (D) Expression of the SMC-specific proteins calponin, α-SMA, SM-MHC, and SM22α in SD-MAPC-SMCs passaged once in expansion medium. Representative example of more than 5 experiments; insets: magnificiation, ×10.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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Referenced in 7 patents
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