Induced Mesenchymal stromal cells derived from iPS cells from aged individuals acquire a rejuvenation signature and a MSC-specific secretome

ABSTRACT: Human induced pluripotent stem cells (iPSCs) - derived mesenchymal stromal cells (iMSCs) are a potentially useful cell type for circumventing ageing-related shortfalls associated with primary mesenchymal or skeletal stromal cells (MSCs/SSCs). To date, the extent of the reflection of ageing-hallmarks in iMSCs differentiated from iPSCs derived from elderly donors remains unclear. In this study, we show that fetal (55 days post conception) femur-derived MSCs and MSCs isolated from aged (60 – 74 years) donors differ in their transcriptome and secretome profile. Yet, iMSCs irrespective of donor age and cell type acquired a rejuvenation gene signature, specifically, INHBE, DNMT3B, POU5F1P1, CDKN1C, GCNT2; also present in pluripotent stem cells but not observed in the parental MSCs. Furthermore, dendrograms generated from the transcriptomes of iMSCs derived from the human embryonic stem cell line H1, fetal and aged MSCs always clustered together with the parental fetal femur-derived MSCs. In addition, these were distinct from MSCs isolated from aged donors when comparing gene ontologies (GOs) related to ageing processes. Critically, in terms of regenerative medicine applications, iMSCs re-acquired a similar secretome (e.g. SERPINE1, SDF-1a, HGF, IL6, IL10, THBS1) to that of the parental fetal MSCs, thus re-enforcing their capabilities of imparting context dependent paracrine signaling.

ORGANISM(S): Homo sapiens

PROVIDER: GSE97311 | GEO | 2019/03/13

REPOSITORIES: GEO