Tissue source determines the differentiation potentials of mesenchymal stem cells: a comparative study of human mesenchymal stem cells from bone marrow and adipose tissue

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0716-x) contains supplementary material, which is available to authorized users.

Phenotypic, Transcriptional, and Functional Analysis of Liver Mesenchymal Stromal Cells and Their Immunomodulatory Properties

“…Consistent with current concepts in the field, BM‐MSCs and A‐MSCs reduced T cell proliferation and IFNγ production in response to allostimulation, had an antiapoptotic effect on T cells in vitro, and their inhibitory impact was reversed by the competitive IDO antagonist 1‐MT . Both the transcriptomes and functional properties of BM‐MSCs and A‐MSCs were similar to each other in their immunomodulatory capacities, although tissue‐related differences in nonimmunological transcripts separated them, consistent with what has been reported before …”

“…(11,12,18) Both the transcriptomes and functional properties of BM-MSCs and A-MSCs were similar to each other in their immunomodulatory capacities, although tissue-related differences in nonimmunological transcripts separated them, consistent with what has been reported before. (28,29) In each experiment, L-MSCs appeared superior to BM-MSCs and A-MSCs in their immunomodulatory properties, regardless of the age or the sex of the donor. The favorable biological properties of L-MSCs were shown in several ways, using different in vitro assays.…”

Characterization of the structure of rabbit anterior cruciate ligament and its stem/progenitor cells

“…These findings indicate that the biological properties of ligament stem/progenitor cells are not only dependent on the anatomic location of the “component tissue” in the ligament, as shown in this study, they also vary among different types of ligaments like ACL and MCL. Indeed, a recent comparative study of human MSCs from bone marrow and adipose tissue SCs suggested that tissue source determines the differentiation potential of MSCs possibly due to the differential methylation status of the transcription factors controlling MSC fate …”

Osteoarthritic Milieu Affects Adipose‐Derived Mesenchymal Stromal Cells

“…A successful strategy to counteract OA would consist of long‐term modulation of degenerative joint environment by simultaneously reducing inflammation and promoting tissue regeneration . ASC can be easily harvested from patients by a simple, minimally invasive procedure and are more abundant than the bone marrow mesenchymal stromal cells (BM‐MSC) . Both stromal cell (SC) types have adipogenic, osteogenic, and chondrogenic differentiation potential and display immunosuppressive properties, both in vitro and in vivo …”