Geriatric fragility fractures are associated with a human skeletal stem cell defect.

Aging Cell
Thomas H AmbrosiCharles K F Chan

Abstract

Fragility fractures have a limited capacity to regenerate, and impaired fracture healing is a leading cause of morbidity in the elderly. The recent identification of a highly purified bona fide human skeletal stem cell (hSSC) and its committed downstream progenitor cell populations provides an opportunity for understanding the mechanism of age-related compromised fracture healing from the stem cell perspective. In this study, we tested whether hSSCs isolated from geriatric fractures demonstrate intrinsic functional defects that drive impaired healing. Using flow cytometry, we analyzed and isolated hSSCs from callus tissue of five different skeletal sites (n = 61) of patients ranging from 13 to 94 years of age for functional and molecular studies. We observed that fracture-activated amplification of hSSC populations was comparable at all ages. However, functional analysis of isolated stem cells revealed that advanced age significantly correlated with reduced osteochondrogenic potential but was not associated with decreased in vitro clonogenicity. hSSCs derived from women displayed an exacerbated functional decline with age relative to those of aged men. Transcriptomic comparisons revealed downregulation of skeletogenic pathways ...Continue Reading

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Citations

Sep 16, 2020·Aging·Thomas H AmbrosiCharles K F Chan
Jan 21, 2021·International Journal of Molecular Sciences·Emerito Carlos Rodríguez-Merchán

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Methods Mentioned

BETA
flow cytometry
FACS
Chip

Software Mentioned

Geneset
GCOS
GEXC
StepMiner
Gene Expression Commons ( GEXC )

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