Endogenous Bone Marrow MSCs Are Dynamic, Fate-Restricted Participants in Bone Maintenance and Regeneration

Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Cell stem cell (Impact Factor: 22.15). 03/2012; 10(3):259-72. DOI: 10.1016/j.stem.2012.02.003

ABSTRACT Mesenchymal stem cells (MSCs) commonly defined by in vitro functions have entered
clinical application despite little definition of their function in residence.
Here, we report genetic pulse-chase experiments that define osteoblastic cells as
short-lived and nonreplicative, requiring replenishment from bone-marrow-derived,
Mx1(+) stromal cells with "MSC" features. These cells respond to tissue stress
and migrate to sites of injury, supplying new osteoblasts during fracture
healing. Single cell transplantation yielded progeny that both preserve
progenitor function and differentiate into osteoblasts, producing new bone. They
are capable of local and systemic translocation and serial transplantation. While
these cells meet current definitions of MSCs in vitro, they are osteolineage
restricted in vivo in growing and adult animals. Therefore, bone-marrow-derived
MSCs may be a heterogeneous population with the Mx1(+) population, representing a
highly dynamic and stress responsive stem/progenitor cell population of
fate-restricted potential that feeds the high cell replacement demands of the
adult skeleton.

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