HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 2005-0551v1 24/11/2355    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zeng, L. Articles by Verfaillie, C. Search for Related Content PubMed PubMed Citation Articles by Zeng, L. Articles by Verfaillie, C.

TISSUE-SPECIFIC STEM CELLS

Multipotent Adult Progenitor Cells from Swine Bone Marrow

^aStem Cell Institute,
^bDepartment of Medicine, Medical School,
^cDepartment of Biomedical Engineering, and
^dVeterinary Population Medicine Department, University of Minnesota, Minneapolis, Minnesota, USA

Key Words. Bone marrow • Cell therapy • Heart failure • Stem cell • Large animal model

Correspondence: Catherine Verfaillie, M.D., Professor of Medicine, Director, Stem Cell Institute, University of Minnesota, McGuire Translational Research Facility, 2001 6th St. SE, Mail Code 2873, Minneapolis, Minnesota 55455, USA. Telephone: 612-625-0602; Fax: 612-624-2436; e-mail: Catherine.Verfaillie{at}med.kuleuven.be

Received November 8, 2005; accepted for publication May 25, 2006.


We show that multipotent adult progenitor cells (MAPCs) can be derived from both postnatal and fetal swine bone marrow (BM). Although swine MAPC (swMAPC) cultures are initially mixed, cultures are phenotypically homogenous by 50 population doublings (PDs) and can be maintained as such for more than 100 PDs. swMAPCs are negative for CD44, CD45, and major histocompatibility complex (MHC) classes I and II; express octamer binding transcription factor 3a (Oct3a) mRNA and protein at levels close to those seen in human ESCs (hESCs); and have telomerase activity preventing telomere shortening even after 100 PDs. Using quantitative-reverse transcription-polymerase chain reaction (Q-RT-PCR), immunofluorescence, and functional assays, we demonstrate that swMAPCs differentiate into chondrocytes, adipocytes, osteoblasts, smooth muscle cells, endothelium, hepatocyte-like cells, and neuron-like cells. Consistent with what we have shown for human and rodent MAPCs, Q-RT-PCR demonstrated a significant upregulation of transcription factors and other lineage-specific transcripts in a time-dependent fashion similar to development. When swMAPCs were passaged for 3–6 passages at high density (2,000–8,000 cells per cm²), Oct3a mRNA levels were no longer detectable, cells acquired the phenotype of mesenchymal stem cells (CD44⁺, MHC class I⁺), and could differentiate into typical mesenchymal lineages (adipocytes, osteoblasts, and chondroblasts), but not endothelium, hepatocyte-like cells, or neuron-like cells. Even if cultures were subsequently replated at low density (approximately 100–500 cells per cm²) for >20 PDs, Oct3a was not re-expressed, nor were cells capable of differentiating to cells other than mesenchymal-type cells. This suggests that the phenotype and functional characteristics of swMAPCs may not be an in vitro culture phenomenon.

This article has been cited by other articles:

				L. Zeng, Q. Hu, X. Wang, A. Mansoor, J. Lee, J. Feygin, G. Zhang, P. Suntharalingam, S. Boozer, A. Mhashilkar, et al. Bioenergetic and Functional Consequences of Bone Marrow-Derived Multipotent Progenitor Cell Transplantation in Hearts With Postinfarction Left Ventricular Remodeling Circulation, April 10, 2007; 115(14): 1866 - 1875. [Abstract] [Full Text] [PDF]