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

By D. Park, J. Spencer, Bong Ihn Koh, Tatsuya Kobayashi, Joji Fujisaki, T. Clemens, Charles P. Lin, H. Kronenberg, D. Scadden. Cell Stem Cell, 2012

618 citations recorded by the source corpus.

SUMMARY 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.

Subfields: Genetics, Hematology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a9a423aab53ffacfa3f172d1e81c4442a8fed7b9

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

1. A. Keating
2. W. Fibbe
3. Maria Ester Bernardo
4. S. Morrison
5. T. Stappenbeck

In Hematology

1. W. Fibbe
2. A. Keating
3. S. Morrison

In Molecular Biology

1. A. Keating
2. S. Morrison
3. G. Karsenty
4. T. Stappenbeck

Citations in the corpus

• Leptin Receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow (2014, positive): “CFU-Fs often expressed Mx1-Cre, consistent with a recent study (Park et al., 2012).”
• Perivascular Gli1+ progenitors are key contributors to injury-induced organ fibrosis (2014, neutral): “Perivascular Gli1+ Cells Expand and Become Myofibroblasts after Injury of Major Organs The MSC is most commonly defined as a cell with trilineage dif- ferentiation capability and CFU-F capacity in vitro (Park et al., 2012).”
• Mesenchymal stromal cells: new directions. (2012, background): “Their recent elegant study of bone maintenance and repair (Park et al., 2012) highlights the importance of genetic tools that better define the in vivo role of BM MSCs.”
• Mesenchymal stromal cells: sensors and switchers of inflammation. (2013, positive): “Park et al. (2012) showed that a subset of Nestin + MSCs present in vivo are able to replace short-lived mature osteoblasts to maintain homeostasis and respond to bone injury.”
• Gremlin 1 Identifies a Skeletal Stem Cell with Bone, Cartilage, and Reticular Stromal Potential (2015, methodology): “CD31 was used to exclude endothelial cells (Park et al., 2012) (Table S1D).”
• Identification and Specification of the Mouse Skeletal Stem Cell (2015, neutral): “…consists of eight different cellular subpopulations with distinct skeletogenic properties and encompasses subpopulations that have characteristics of described skeletogenic cell types identified by lineage tracing (Bianco, 2014, Méndez-Ferrer et al., 2010; Park et al., 2012; Zhou et al., 2014).”