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

Bustos, Martha L.; Huleihel, Luai; Kapetanaki, Maria G.; Cardenas, Christian L. Lino; Mroz, Lyle; Ellis, Bryon; McVerry, Bryan J.; Richards, Thomas J.; Kaminski, Naftali; Cerdenes, Nayra; Mora, Ana L.; Rojas, Mauricio

doi:10.1164/rccm.201306-1043oc

Cited by 166 publications

(133 citation statements)

References 77 publications

Supporting

Mentioning

131

Contrasting

Order By: Relevance

“…MSC treatment was beneficial only in aged mice (8-12 mo of age). Age affects various MSC functions, including expression and secretion of soluble factors important in recovery from lung injury (20). Aged animals show lower expression of genes involved in cell activation and migration and of cytokine receptors (e.g., TNFR1 and TNFR2) and chemokine receptors (CCR7, CX3CR1, and CXCR5) involved in MSC migration and chemotaxis (21).…”

Section: Discussionmentioning

confidence: 99%

Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo

Chan

Kuok

Leung

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

184

181

View full text Add to dashboard Cite

Influenza can cause acute lung injury. Because immune responses often play a role, antivirals may not ensure a successful outcome. To identify pathogenic mechanisms and potential adjunctive therapeutic options, we compared the extent to which avian influenza A/H5N1 virus and seasonal influenza A/H1N1 virus impair alveolar fluid clearance and protein permeability in an in vitro model of acute lung injury, defined the role of virus-induced soluble mediators in these injury effects, and demonstrated that the effects are prevented or reduced by bone marrow-derived multipotent mesenchymal stromal cells. We verified the in vivo relevance of these findings in mice experimentally infected with influenza A/H5N1. We found that, in vitro, the alveolar epithelium’s protein permeability and fluid clearance were dysregulated by soluble immune mediators released upon infection with avian (A/Hong Kong/483/97, H5N1) but not seasonal (A/Hong Kong/54/98, H1N1) influenza virus. The reduced alveolar fluid transport associated with down-regulation of sodium and chloride transporters was prevented or reduced by coculture with mesenchymal stromal cells. In vivo, treatment of aged H5N1-infected mice with mesenchymal stromal cells increased their likelihood of survival. We conclude that mesenchymal stromal cells significantly reduce the impairment of alveolar fluid clearance induced by A/H5N1 infection in vitro and prevent or reduce A/H5N1-associated acute lung injury in vivo. This potential adjunctive therapy for severe influenza-induced lung disease warrants rapid clinical investigation.

show abstract

Section: Discussionmentioning

confidence: 99%

Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo

Chan

Kuok

Leung

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

184

181

View full text Add to dashboard Cite

show abstract

“…Moreover, dysfunction of other potential progenitor cell types, such as mesenchymal stromal cells (MSCs), has been associated with reduced repair capacity in a murine post-pneumectomy model [121]. BUSTOS et al [122] found diminished anti-inflammatory potential of bone marrow-derived MSCs from old mice. [20].…”

Section: Stem Cell Exhaustionmentioning

confidence: 99%

Hallmarks of the ageing lung

2015

View full text Add to dashboard Cite

Ageing is the main risk factor for major non-communicable chronic lung diseases, including chronic obstructive pulmonary disease, most forms of lung cancer and idiopathic pulmonary fibrosis. While the prevalence of these diseases continually increases with age, their respective incidence peaks at different times during the lifespan, suggesting specific effects of ageing on the onset and/or pathogenesis of chronic obstructive pulmonary disease, lung cancer and idiopathic pulmonary fibrosis. Recently, the nine hallmarks of ageing have been defined as cell-autonomous and non-autonomous pathways involved in ageing. Here, we review the available evidence for the involvement of each of these hallmarks in the pathogenesis of chronic obstructive pulmonary disease, lung cancer, or idiopathic pulmonary fibrosis. Importantly, we propose an additional hallmark, "dysregulation of the extracellular matrix", which we argue acts as a crucial modifier of cell-autonomous changes and functions, and as a key feature of the above-mentioned lung diseases. @ERSpublications Hallmarks of ageing are selecting factors for the pathogenesis of COPD, lung cancer and IPF

show abstract

“…13 Researchers also probably do not fully appreciate the inherent diff erences between MSCs cultured from diff erent donors 82 and are only beginning to appreciate how age might aff ect MSC function. 83 Finally, we remain unable to answer defi nitively basic mechanistic questions, such as how MSCs have a therapeutic eff ect on non-pulmonary tissue when given intravenously. MSCs become trapped in the lung after intravenous administration, yet have benefi cial eff ects in traumatic brain injury and myocardial infarction (supporting the presence of secreted paracrine factors).…”

Section: Mitochondrial Transfermentioning

confidence: 99%

Mesenchymal stem cells: mechanisms of potential therapeutic benefit in ARDS and sepsis

Walter

Ware

Matthay

2014

The Lancet Respiratory Medicine

240

212

View full text Add to dashboard Cite

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

Abstract: 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.

Cited by 166 publications

References 77 publications

Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo

Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo

Hallmarks of the ageing lung

Mesenchymal stem cells: mechanisms of potential therapeutic benefit in ARDS and sepsis

Contact Info

Product

Resources

About