Pluripotency of mesenchymal stem cells derived from adult marrow

Pluripotency of mesenchymal stem cells derived from adult marrow

JULY 2002 | Yuehua Jiang, Balkrishna N. Jahagirdar, R. Lee Reinhardt, Robert E. Schwartz, C. Dirk Keene, Xilma R. Ortiz-Gonzalez, Morayma Reyes, Todd Lenvik, Troy Lund, Mark Blackstad, Jingbo Du, Sara Aldrich, Aaron Lisberg, Walter C. Low, David A. Largaespada & Catherine M. Verfaillie
Mesenchymal stem cells (MSCs) derived from adult marrow, termed multipotent adult progenitor cells (MAPCs), exhibit pluripotency, differentiating into cells of the three germ layers—mesoderm, neuroectoderm, and endoderm—in vitro. When injected into an early blastocyst, single MAPCs contribute to most, if not all, somatic cell types. In vivo, MAPCs engraft and differentiate into haematopoietic lineage cells and epithelial cells of the liver, lung, and gut. Engraftment in the haematopoietic system and gastrointestinal tract is enhanced in minimally irradiated hosts. MAPCs proliferate extensively without senescence or loss of differentiation potential, making them ideal for therapy of inherited or degenerative diseases. Embryonic stem (ES) cells are pluripotent and can differentiate into all cell lineages, but their use is limited by ethical concerns. Tissue-specific stem cells, including haematopoietic, neural, gastrointestinal, epidermal, hepatic, and mesenchymal stem cells, have less self-renewal ability and are not pluripotent. Recent studies suggest that tissue-specific stem cells can differentiate into lineages other than their tissue of origin. For example, bone marrow or haematopoietic stem cells have been shown to differentiate into skeletal myoblasts, cardiac myoblasts, endothelium, hepatic and biliary duct epithelium, lung, gut, and neuroectodermal cells. A rare cell within human bone marrow MSC cultures, the MAPC, can be expanded for over 80 population doublings. These cells differentiate into mesenchymal, endothelial, and endodermal cells. In rodent bone marrow, MAPCs can be cultured for over 120 population doublings. They express markers similar to human MAPCs but differ from murine haematopoietic stem cells with transdifferentiation potential. MAPCs have a large nucleus and scant cytoplasm, with telomere length remaining stable over 100 population doublings. In vitro, MAPCs differentiate into endothelial, neuroectodermal, and endodermal cells. For example, when cultured with vascular endothelial growth factor (VEGF), MAPCs acquire an endothelial phenotype. When cultured with basic fibroblast growth factor (bFGF), they differentiate into astrocytes, oligodendrocytes, and neurons. When cultured with FGF-4 and hepatocyte growth factor (HGF), they differentiate into hepatocytes with functional characteristics. In vivo, single MAPCs contribute to most somatic tissues when injected into a blastocyst. Chimaerism was detected in 80% of mice derived from blastocysts with 10–12 MAPCs and 33% from those with a single MAPC.Mesenchymal stem cells (MSCs) derived from adult marrow, termed multipotent adult progenitor cells (MAPCs), exhibit pluripotency, differentiating into cells of the three germ layers—mesoderm, neuroectoderm, and endoderm—in vitro. When injected into an early blastocyst, single MAPCs contribute to most, if not all, somatic cell types. In vivo, MAPCs engraft and differentiate into haematopoietic lineage cells and epithelial cells of the liver, lung, and gut. Engraftment in the haematopoietic system and gastrointestinal tract is enhanced in minimally irradiated hosts. MAPCs proliferate extensively without senescence or loss of differentiation potential, making them ideal for therapy of inherited or degenerative diseases. Embryonic stem (ES) cells are pluripotent and can differentiate into all cell lineages, but their use is limited by ethical concerns. Tissue-specific stem cells, including haematopoietic, neural, gastrointestinal, epidermal, hepatic, and mesenchymal stem cells, have less self-renewal ability and are not pluripotent. Recent studies suggest that tissue-specific stem cells can differentiate into lineages other than their tissue of origin. For example, bone marrow or haematopoietic stem cells have been shown to differentiate into skeletal myoblasts, cardiac myoblasts, endothelium, hepatic and biliary duct epithelium, lung, gut, and neuroectodermal cells. A rare cell within human bone marrow MSC cultures, the MAPC, can be expanded for over 80 population doublings. These cells differentiate into mesenchymal, endothelial, and endodermal cells. In rodent bone marrow, MAPCs can be cultured for over 120 population doublings. They express markers similar to human MAPCs but differ from murine haematopoietic stem cells with transdifferentiation potential. MAPCs have a large nucleus and scant cytoplasm, with telomere length remaining stable over 100 population doublings. In vitro, MAPCs differentiate into endothelial, neuroectodermal, and endodermal cells. For example, when cultured with vascular endothelial growth factor (VEGF), MAPCs acquire an endothelial phenotype. When cultured with basic fibroblast growth factor (bFGF), they differentiate into astrocytes, oligodendrocytes, and neurons. When cultured with FGF-4 and hepatocyte growth factor (HGF), they differentiate into hepatocytes with functional characteristics. In vivo, single MAPCs contribute to most somatic tissues when injected into a blastocyst. Chimaerism was detected in 80% of mice derived from blastocysts with 10–12 MAPCs and 33% from those with a single MAPC.
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