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2014 ; 189
(7
): 787-98
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Aging mesenchymal stem cells fail to protect because of impaired migration and
antiinflammatory response
#MMPMID24559482
Bustos ML
; Huleihel L
; Kapetanaki MG
; Lino-Cardenas CL
; Mroz L
; Ellis BM
; McVerry BJ
; Richards TJ
; Kaminski N
; Cerdenes N
; Mora AL
; Rojas M
Am J Respir Crit Care Med
2014[Apr]; 189
(7
): 787-98
PMID24559482
show ga
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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