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

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

Research output: Contribution to journalArticle

141 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3139-3149
Number of pages11
JournalJournal of Clinical Investigation
Volume116
Issue number12
DOIs
StatePublished - Dec 1 2006
Externally publishedYes

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Smooth Muscle Myocytes
Stem Cells
Cytokines
Smooth Muscle
Serotonin Receptor Agonists
L-Type Calcium Channels
rho-Associated Kinases
Muscle Development
Serum-Free Culture Media
Tissue Engineering
Fibrin
Blood Vessels
Cell Differentiation
Fungi
Swine
Bone Marrow
Phenotype
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ross, J. J., Hong, Z., Willenbring, B., Zeng, L., Isenberg, B., Eu, H. L., ... Verfaillie, C. M. (2006). Cytokine-induced differentiation of multipotent adult progenitor cells into functional smooth muscle cells. Journal of Clinical Investigation, 116(12), 3139-3149. https://doi.org/10.1172/JCI28184

Cytokine-induced differentiation of multipotent adult progenitor cells into functional smooth muscle cells. / Ross, Jeffrey J.; Hong, Zhigang; Willenbring, Ben; Zeng, Lepeng; Isenberg, Brett; Eu, Han Lee; Reyes Gil, Morayma; Keirstead, Susan A.; Weir, E. Kenneth; Tranquillo, Robert T.; Verfaillie, Catherine M.

In: Journal of Clinical Investigation, Vol. 116, No. 12, 01.12.2006, p. 3139-3149.

Research output: Contribution to journalArticle

Ross, JJ, Hong, Z, Willenbring, B, Zeng, L, Isenberg, B, Eu, HL, Reyes Gil, M, Keirstead, SA, Weir, EK, Tranquillo, RT & Verfaillie, CM 2006, 'Cytokine-induced differentiation of multipotent adult progenitor cells into functional smooth muscle cells', Journal of Clinical Investigation, vol. 116, no. 12, pp. 3139-3149. https://doi.org/10.1172/JCI28184
Ross, Jeffrey J. ; Hong, Zhigang ; Willenbring, Ben ; Zeng, Lepeng ; Isenberg, Brett ; Eu, Han Lee ; Reyes Gil, Morayma ; Keirstead, Susan A. ; Weir, E. Kenneth ; Tranquillo, Robert T. ; Verfaillie, Catherine M. / Cytokine-induced differentiation of multipotent adult progenitor cells into functional smooth muscle cells. In: Journal of Clinical Investigation. 2006 ; Vol. 116, No. 12. pp. 3139-3149.
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