Aging Mesenchymal Stem Cells Fail to Protect Because of Impaired Migration and Antiinflammatory Response

Overview

Journal Am J Respir Crit Care Med

Specialty Critical Care

Date 2014 Feb 25

PMID 24559482

Citations 103

Authors

Martha L Bustos

Luai Huleihel

Maria G Kapetanaki

Christian L Lino-Cardenas

Lyle Mroz

Bryon M Ellis

Bryan J McVerry

Thomas J Richards

Naftali Kaminski

Nayra Cerdenes

Ana L Mora

Mauricio Rojas

Affiliations

Soon will be listed here.

Abstract

Rationale: Aging is characterized by functional impairment and reduced capacity to respond appropriately to environmental stimuli and injury. With age, there is an increase in the incidence and severity of chronic and acute lung diseases. However, the relationship between age and the lung's reduced ability to repair is far from established and necessitates further research in the field.

Objectives: Little is currently known about age-related phenomena in mesenchymal stem cells (MSCs). On account of their ability to protect the endothelium and the alveolar epithelium through multiple paracrine mechanisms, we looked for adverse effects that aging might cause in MSC biology. Such age-related changes might partly account for the increased susceptibility of the aging lung to injury.

Measurements And Main Results: We demonstrated that old mice have more inflammation in response to acute lung injury. To investigate the causes, we compared the global gene expression of aged and young bone marrow-derived MSCs (B-MSCs). Our results revealed that the expression levels of inflammatory response genes depended on the age of the B-MSCs. We demonstrated that the age-dependent decrease in expression of several cytokine and chemokine receptors is important for the migration and activation of B-MSCs. Finally, we showed by adoptive transfer of aged B-MSCs to young endotoxemic mice that aged cells lacked the antiinflammatory protective effect of their young counterparts.

Conclusions: Taken together, the decreased expression of cytokine and chemokine receptors in aged B-MSCs compromises their protective role by perturbing the potential of B-MSCs to become activated and mobilize to the site of injury.

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