Does donor age matter? Biological and immunogenic differences between infant and aged mesenchymal stromal cells

Abstract

Over the last decades, mesenchymal stromal cells MSC) have emerged as a promising therapeutic tool for cell-based therapies. However, their biological characteristics and beneficial potential may decline with patients’ age. Because most patients amenable for regenerative medicine have increased age, this could dramatically limit the autologous use of MSCs. We therefore sought to characterize the biological, immunological, and angiogenetic capacities of infant (iMSCs) versus aged MSCs (aMSCs). Both iMSCs and aMSCs showed typical spindle-shaped morphology, plastic adherence, and the same potential to differentiate into osteogenic, chondrogenic and adipogenic lineages. iMSCs and aMSCs expressed MSC-typical surface markers such as CD90 and CD105 and were negative for CD45, CD34, CD31 and CD117. iMSCs showed faster in vitro proliferation (p<0.001), migration (p<0.001), and stronger endothelial adhesion (p=0.018) than aMSC. There were no differences in HLA class I, β2 microglobulin, HLA class II, and co-stimulatory molecule expression between iMSCs and aMSCs. Both immunogenic HLA class II and CD54 and tolerogenic HLA-E expression were upregulated by IFNγ. iMSCs showed significantly higher CD29 signals and stronger endothelial adhesion than aMSCs. Interestingly, iMSCs outperformed aMSCs in different angiogenesis parameters. If not used in an autologous setting, iMSCs and aMSCs similarly provoked T_H1 and T_H2 responses in unidirectional ELISPOT assays and donor-specific IgM antibody production. Our results thus suggest that donor age does not affect immunogenicity and immunomodulatory properties, but markedly reduces biological properties of proliferation, migration, adhesion, and limits their angiogenic effects.