Leptin Receptor Identified a Mesenchymal Stromal Cell Biomarker

The Leptin Receptor (LepR) has been identified as a biomarker for the progenitor cells that are the major source of bone and adipocytes in adult bone marrow.

Studies of the identity and physiological function of mesenchymal stromal cells (MSCs) have been hampered by a lack of markers that permit both prospective identification and fate mapping in vivo. A partial solution to this problem was presented in a recent paper that reported that LepR was a marker that highly enriched bone marrow MSCs.

The LepR protein belongs to the gp130 family of cytokine receptors that are known to stimulate gene transcription via activation of cytosolic STAT proteins. This protein is a receptor for leptin (an adipocyte-specific hormone that regulates body weight), and is involved in the regulation of fat metabolism, as well as in a novel hematopoietic pathway that is required for normal lymph cell synthesis. Mutations in this gene have been associated with obesity and pituitary dysfunction.

Investigators at the University of Texas Southwestern Medical Center (Dallas, USA) found that approximately 0.3% of bone marrow cells were LepR+, 10% of which were CFU-Fs, accounting for 94% of bone marrow CFU-Fs. CFU-Fs are colony-forming unit-fibroblasts that are obtained when bone marrow mononuclear cells are plated directly into cell culture plates or flasks. Mesenchymal stem cells, but not red blood cells or hematopoetic progenitors, are adherent to tissue culture plastic within 24 to 48 hours.

The investigators showed that LepR+ cells were the major source of bone and adipocytes in adult bone marrow. They arose postnatally and gave rise to most bone and adipocytes formed in adult bone marrow, including bone regenerated after irradiation or fracture, and while LepR+ cells were normally quiescent, they proliferated after injury.

“There has been an increasing amount of clinical interest in MSCs, but advances have been slow because researchers to date have been unable to identify MSCs and study their normal physiological function in the body,” said senior author Dr. Sean Morrison, professor of pediatrics at the University of Texans Southwestern Medical Center. “We found that a protein known as leptin receptor can serve as a biomarker to accurately identify MSCs in adult bone marrow in vivo, and that those MSCs are the primary source of new bone formation and bone repair after injury.”

The study was published in the June 19, 2014, online edition of the journal Cell Stem Cell.

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University of Texas Southwestern Medical Center