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: 22.27). 03/2012; 10(3):259-72. DOI: 10.1016/j.stem.2012.02.003


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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    • "Mesenchymal stem cells (MSCs), osteogenic stem cells residing in the bone marrow stroma (also named bone marrow stromal cells), have been long considered highly plastic multipotent precursors, able to commit toward diversified lineages, including non-mesodermal ones. Their in vitro plasticity and ease of processing prompted their wide, sometimes untimely, exploitation in diversified regenerative medicine applications (Park et al., 2012;Bianco et al., 2013). They have been tested also for their putative, yet widely debated, neuroregenerative potential. "

    Full-text · Article · Jan 2016 · Frontiers in Cellular Neuroscience
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    • "SSCs are mitotic, self-renewing, " oligopotent " elements, giving rise to cell progenies of bone tissue (osteoblasts and chondrocytes; Bianco et al., 2013a,b; Chan et al., 2013). Subsequent osteoblast progenies are endowed with an intense cell renewal potential and undergo relatively rapid turnover (Park et al., 2012). The entire and complex BM niche is maintained through constant interactions with vasculature and stromal components that regulate self-renewal and differentiation of SCs and early progenitors (Méndez-Ferrer et al., 2010; Ding et al., 2012). "
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    ABSTRACT: Although therapeutic use of stem cells (SCs) is already available in some tissues (cornea, blood, and skin), in most organs we are far from reaching the translational goal of regenerative medicine. In the nervous system, due to intrinsic features which make it refractory to regeneration/repair, it is very hard to obtain functionally integrated regenerative outcomes, even starting from its own SCs (the neural stem cells; NSCs). Besides NSCs, mesenchymal stem cells (MSCs) have also been proposed for therapeutic purposes in neurological diseases. Yet, direct (regenerative) and indirect (bystander) effects are often confused, as are MSCs and bone marrow-derived (stromal, osteogenic) stem cells (BMSCs), whose plasticity is actually overestimated (i.e., trans-differentiation along non-mesodermal lineages, including neural fates). In order to better understand failure in the “regenerative” use of SCs for neurological disorders, it could be helpful to understand how NSCs and BMSCs have adapted to their respective organ niches. In this perspective, here the adult osteogenic and neurogenic niches are considered and compared within their in vivo environment.
    Full-text · Article · Nov 2015 · Frontiers in Cellular Neuroscience
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    • "Osterix (OSX) is a transcription factor that is expressed by precursors that first appear in the perichondrium and invade primary ossification centers in parallel with blood vessels to give rise to mature bone cells (Maes et al., 2010; Nakashima et al., 2002). Until recently, OSX-expressing cells were thought to be committed progenitors that transiently contribute to bone remodeling at least in adult mice (Park et al., 2012). However, perinatal OSX+ cells appear to contain MSCs that demonstrated high CFU-F activity in addition to the ability of trilineage differentiation in vitro (Mizoguchi et al., 2014). "
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    ABSTRACT: Mesenchymal stromal cells (MSCs) are heterogeneous and primitive cells discovered first in the bone marrow (BM). They have putative roles in maintaining tissue homeostasis and are increasingly recognized as components of stem cell niches, which are best defined in the blood. The absence of in vivo MSC markers has limited our ability to track their behavior in vivo and draw comparisons with in vitro observations. Here we review the historical background of BM-MSCs, advances made in their prospective isolation, their developmental origin and contribution to maintaining subsets of hematopoietic cells, and how mesenchymal cells contribute to other stem cell niches. Copyright © 2015 Elsevier Inc. All rights reserved.
    Full-text · Article · Mar 2015 · Cell Stem Cell
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