Human mesenchymal stem cells self-renew and differentiate according to a deterministic hierarchy

Mesenchymal progenitor cells (MPCs) have been isolated from a variety of connective tissues, and are commonly called "mesenchymal stem cells" (MSCs). A stem cell is defined as having robust clonal self-renewal and multilineage differentiation potential. Accordingly, the term "MSC"...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2009-08, Vol.4 (8), p.e6498-e6498
Main Authors: Sarugaser, Rahul, Hanoun, Lorraine, Keating, Armand, Stanford, William L, Davies, John E
Format: Article
Language:English
Subjects:
Antigens
Biomedical engineering
Biomedical materials
Bone healing
Bone marrow
Breast cancer
Cartilage
Cell Biology
Cell Differentiation
Cell Division
Cell self-renewal
Cells (biology)
Cells, Cultured
Cloning
Collagen
Connective tissues
Cytogenetics
Developmental Biology/Cell Differentiation
Developmental Biology/Stem Cells
Differentiation
Engineering
Fibroblasts
Fluorescence
Fluorescence in situ hybridization
Gene expression
Humans
Mesenchymal stem cells
Mesenchymal Stem Cells - cytology
Mesenchyme
Metastasis
Osteoporosis
Phosphatase
Rodents
Stem cells
Stroma
Studies
Tissues
Umbilical cord
Y chromosomes
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Mesenchymal progenitor cells (MPCs) have been isolated from a variety of connective tissues, and are commonly called "mesenchymal stem cells" (MSCs). A stem cell is defined as having robust clonal self-renewal and multilineage differentiation potential. Accordingly, the term "MSC" has been criticised, as there is little data demonstrating self-renewal of definitive single-cell-derived (SCD) clonal populations from a mesenchymal cell source. Here we show that a tractable MPC population, human umbilical cord perivascular cells (HUCPVCs), was capable of multilineage differentiation in vitro and, more importantly, contributed to rapid connective tissue healing in vivo by producing bone, cartilage and fibrous stroma. Furthermore, HUCPVCs exhibit a high clonogenic frequency, allowing us to isolate definitive SCD parent and daughter clones from mixed gender suspensions as determined by Y-chromosome fluorescent in situ hybridization. Analysis of the multilineage differentiation capacity of SCD parent clones and daughter clones enabled us to formulate a new hierarchical schema for MSC self-renewal and differentiation in which a self-renewing multipotent MSC gives rise to more restricted self-renewing progenitors that gradually lose differentiation potential until a state of complete restriction to the fibroblast is reached.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0006498