Appendix J. 
Multipotent Adult Progenitor Cells: An Update 
CATHERINE M. VERFAILLIE, M.D. 
Division of Hematology, Department of Medicine, and Stem Cell 
Institute, 
University of Minnesota 
INTRODUCTION: 
In this paper, we want to provide updated information 
regarding a rare cell population, we have named, multipotent adult 
progenitor cells or MAPC. In 2001-2002, we published a series of 
papers demonstrating that while attempting to select and culture 
mesenchymal stem cells (MSC) from human and subsequently mouse 
and rat bone marrow (BM), we accidentally identified a rare 
population of cells that has characteristics unlike most adult somatic 
stem cells in that they appear to proliferate v\hthout senescence, and 
have pluripotent differentiation ability in vitro and in vivo 
Phenotype of Bone Marrow MAPC: MAPC can be cultured 
from human, mouse and rat bone marrow (BM). Unlike MSC, MAPC 
do not express major histocompatibiliy (MHC)- class I antigens, do 
not express, or express only low levels of, the CD44 antigen, and are 
CD105 (also endoglin, or SH2) negative Unlike hematopoietic stem 
cells (HSC), MAPC do not express CD45, CD34, and cKit but like 
HSC, MAPC express Thyl, AC 133 (human MAPC) and Seal (mouse) 
albeit at low levels .In the mouse, MAPC express low levels of 
stage specific embryonic antigen (SSEA)-l, and express low levels of 
the transcription factors Oct4 and Rexl, known to be important for 
maintaining embryonic stem (ES) cells undifferentiated ^ and to be 
down-regulated when ES cells undergo somatic cell commitment and 
differentiation 
MAPC can also be isolated from other tissues, and other species: 
We also showed that MAPC can be cultured from mouse 
brain and mouse muscle Of note, the diherentiation potential and 
expressed gene profile of MAPC derived from the different tissues 
appears to be highly similar. These studies used whole brain and 
muscle tissue as the initiating cell population, therefore containing 
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