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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 Stem cells

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 1

Effects of TGF-β1, PDGF-BB, or TGF-β1 plus PDGF-BB on SD-MAPC morphology.

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Effects of TGF-β1, PDGF-BB, or TGF-β1 plus PDGF-BB on SD-MAPC morphology...
Phase-contrast images of SD-MAPCs (A); SD-MAPCs treated for 6 days in serum-free medium with 5 ng/ml PDGF-BB (B), 2.5 ng/ml TGF-β1 (C), or 5 ng/ml PDGF-BB and 2.5 ng/ml TGF-β1 (D); or primary RAOSMCs (E). Morphology is representative of more than 10 independent experiments. Magnification, ×10. Phalloidin staining (A–E, insets; magnification, ×10) demonstrates that the stress fiber pattern of SD-MAPCs induced with TGF-β1 or TGF-β1 plus PDGF-BB is similar to that of primary RAOSMCs (E). (F) Cellular density on day 6 of SD-MAPC differentiation (P < 0.01; n = 4).

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

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