Abstract
Mesenchymal stromal/stem cells (MSCs) reside in many human tissues and comprise a heterogeneous population of cells with self-renewal and multi-lineage differentiation potential, making them useful in regenerative medicine. It remains inconclusive whether MSCs isolated from different tissue sources exhibit variations in biological features. In this study, we derived MSCs from adipose tissue (AT-MSC) and compact bone (CB-MSC). We found that early passage of MSCs was readily expandable ex vivo, whereas the prolonged culture of MSCs showed alteration of cell morphology to fibroblastoid and reduced proliferation. CB-MSCs and AT-MSCs at passage 3 were CD29+, CD44+, CD105+, CD106+, and Sca-1+; however, passage 7 MSCs showed a reduction of MSC markers, indicating loss of stem cell population after prolonged culturing. Strikingly, CB-MSC was found more efficient at undergoing osteogenic differentiation, while AT-MSC was more efficient to differentiate into adipocytes. The biased differentiation pattern of MSCs from adipogenic or osteogenic tissue source was accompanied by preferential expression of the corresponding lineage marker genes. Interestingly, CB-MSCs treated with DNA demethylation agent 5-azacytidine showed enhanced osteogenic and adipogenic differentiation, whereas the treated AT-MSCs are less competent to differentiate. Our results suggest that the epigenetic state of MSCs is associated with the biased differentiation plasticity towards its tissue of origin, proposing a mechanism related to the retention of epigenetic memory. These findings facilitate the selection of optimal tissue sources of MSCs and the ex vivo expansion period for therapeutic applications.
Highlights
Mesenchymal stromal cells (MSCs), referred to mesenchymal stem cells [1], represent a heterogeneous population of cells that can be isolated from a wide range of tissues, including bone marrow, compact bone, placenta and adipose tissue [2,3,4,5,6]
Murine MSCs isolated from the adipose tissue (AT) and compact bone (CB) were expanded ex vivo
The P7 MSCs of both types appeared to have weaker positive staining patterns when compared to the early P3 samples. These results suggest that MSCs derived from different tissue origins exhibit differentiation bias and their differentiation capacities reduce after prolonged culture
Summary
Mesenchymal stromal cells (MSCs), referred to mesenchymal stem cells [1], represent a heterogeneous population of cells that can be isolated from a wide range of tissues, including bone marrow, compact bone, placenta and adipose tissue [2,3,4,5,6]. MSC was first isolated from mouse bone marrow as fibroblast colony-forming units, which were distinguished by their ability to adhere to plastic culture dishes [2]. They display fibroblastic morphology and are capable of differentiation to chondrocytes, adipocytes, and osteoblasts in vitro [1,7]. MSCs are intensely studied in clinical research because of their multi-lineage potential and ease of isolation and culture [1,12]. Their ability to evade the host immune system by suppressing
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