Abstract
BackgroundMesenchymal stem cells (MSCs) possess intrinsic regeneration capacity as part of the repair process in response to injury, such as fracture or other tissue injury. Bone marrow and adipose tissue are the major sources of MSCs. However, which cell type is more effective and suitable for cell therapy remains to be answered. The intrinsic molecular mechanism supporting the assertion has also been lacking.MethodsHuman bone marrow-derived MSCs (BMSCs) and adipose tissue-derived MSCs (ATSCs) were isolated from bone marrow and adipose tissue obtained after total hip arthroplasty. ATSCs and BMSCs were incubated in standard growth medium. Trilineage differentiation including osteogenesis, adipogenesis, and chondrogenesis was performed by addition of relevant induction mediums. The expression levels of trilineage differentiation marker genes were evaluated by quantitative RT-PCR. The methylation status of CpG sites of Runx2, PPARγ, and Sox9 promoters were checked by bisulfite sequencing. In addition, ectopic bone formation and calvarial bone critical defect models were used to evaluate the bone regeneration ability of ATSCs and BMSCs in vivo.ResultsThe results showed that BMSCs possessed stronger osteogenic and lower adipogenic differentiation potentials compared to ATSCs. There was no significant difference in the chondrogenic differentiation potential. The CpG sites of Runx2 promoter in BMSCs were hypomethylated, while in ATSCs they were hypermethylated. The CpG sites of PPARγ promoter in ATSCs were hypomethylated, while in BMSCs they were hypermethylated. The methylation status of Sox9 promoter in BMSCs was only slightly lower than that in ATSCs.ConclusionsThe epigenetic memory obtained from either bone marrow or adipose tissue favored MSC differentiation along an osteoblastic or adipocytic lineage. The methylation status of the main transcription factors controlling MSC fate contributes to the differential differentiation capacities of different source-derived MSCs.
Highlights
Mesenchymal stem cells (MSCs) possess intrinsic regeneration capacity as part of the repair process in response to injury, such as fracture or other tissue injury
Compare osteogenesis of Adipose tissue-derived MSC (ATSC) and Bone marrow-derived MSC (BMSC) in vitro In order to compare the osteogenic differentiation potential capacities of ATSCs and BMSCs, MSCs were treated with osteogenic induction medium (OIM) for several days and the mRNA expression levels of genes related to osteogenesis were detected by quantitative real-time RT-PCR
The results showed that after 14 days of OIM induction, mineralization was seen in BMSCs upon osteogenic induction, while there were very few Alizarin Red S-positive calcium nodules formed in the ATSC group (Fig. 2e, f )
Summary
Mesenchymal stem cells (MSCs) possess intrinsic regeneration capacity as part of the repair process in response to injury, such as fracture or other tissue injury. Bone marrow and adipose tissue are the major sources of MSCs. which cell type is more effective and suitable for cell therapy remains to be answered. Low cell survival rate and differentiation capacity in vivo after MSC transplantation have significantly reduced the effectiveness of stem cell therapy [2,3,4,5]. Bone marrow-derived MSCs (BMSCs) and adipose tissue-derived MSCs (ATSCs) are still the main source of MSCs, especially in autologous cell-based therapies, due to ease of harvest and potential autologous application [6]. Despite different gene expression and differentiation capacities have been observed among ATSCs and BMSCs, the underlying mechanisms regarding epigenetic regulation are yet to be investigated
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