The Influence of Donor Age and In Vitro Expansion on the Proliferation and Differentiation Properties of Donor-matched Bone Marrow and Adipose-derived Mesenchymal Stem Cells: Implications for Musculoskeletal Tissue Engineering

摘要: Introduction: Mesenchymal stem cells (MSC) offer a novel cell therapy within tissue engineering and regenerative medicine (TERM)-based strategies, the prospect of MSC therapies are widening since discovery MSCs multiple locations body including bone marrow (BM-MSCs) adipose tissue, (AD-MSCs). It is highly recognised that an organisms reparative potential declines with advancing age, therefore aged patients one primary target populations for TERM applications. Although information available regarding effects patient age on quality human BM-MSCs, little conflicting currently exists AD-MSCs. In addition, few studies have compared freshly isolated expanded donor-matched BM AD-MSCs to elucidate more appropriate source. This study investigated effect donor in vitro ageing functional behaviour (i.e. senescence state, population kinetics differentiation potential) AD-MSCs.Methods: The influence mature (28-55 years) elderly (75-86 was assessed upon isolation (early life-span) during extended (mid late lifespan) timepoints through culture. During culture were characterised cumulative doublings (CPDs) expression associated marker genes, p16INK4A, p21 p53, transcription factor NANOG. At each lifespan telomere length along efficiency osteogenic, adipogenic chondrogenic lineages lineage specific genes histological staining.Results: Elderly displayed similar characteristics terms initial CPD number, p21, p53 NANOG expression, osteogenic lineages. With increasing there significant decline p16INK4A whilst all markers significantly decreased comparable majority outcome measures exception which superior BM-MSCs COL2A1 staining proteoglycans. Donor had negative long-term leading longer PD time lengths. Similar between Increasing both sources complete loss capacity capacity; however only Differentiation after showed ability yet apparent AD-MSCs, ECM deposition.Conclusions: conclusion source will need be considered depending type regeneration required. clinical would greater using early stages culture, as expansion has detrimental properties