Abstract
CD271 is a marker of bone marrow MSCs with enhanced differentiation capacity for bone or cartilage repair. However, the nature of CD271+ MSCs from adipose tissue (AT) is less well understood. Here, we investigated the differentiation, wound healing and angiogenic capacity of plastic adherent MSCs (PA MSCs) versus CD271+ MSCs from AT. There was no difference in the extent to which PA MSCs and CD271+ MSCs formed osteoblasts, adipocytes or chondrocytes in vitro. In contrast, CD271+ MSCs transplanted into athymic rats significantly enhanced osteochondral wound healing with reduced vascularisation in the repair tissue compared to PA MSCs and control animals; there was little histological evidence of mature articular cartilage formation in all animals. Conditioned medium from CD271+ MSC cultures was less angiogenic than PA MSC conditioned medium, and had little effect on endothelial cell migration or endothelial tubule formation in vitro. The low angiogenic activity of CD271+ MSCs and improved early stage tissue repair of osteochondral lesions when transplanted, along with a comparable differentiation capacity along mesenchymal lineages when induced, suggests that these selected cells are a better candidate than PA MSCs for the repair of cartilaginous tissue.
Highlights
Regenerative medicines using stem cells and/or tissue engineering approaches are expected to play a major role in the development of new healthcare in the 21st century, with much current interest and research activity
The properties of selected adipose tissue (AT) mesenchymal stromal/stem cells (MSCs) subpopulations have been less extensively researched than bone marrow MSCs (BM MSCs), two studies have reported that CD271-selected adipose tissue-derived MSCs (AT MSCs) have an enhanced proliferative capacity compared with unsorted plastic adherent (PA MSCs), which is how MSCs are generally isolated from tissue harvests, with differentiation capacity to form chondrocyte-like cells, osteoblasts and adipocytes in vitro[30,31]
There were no significant differences in the extent of plastic adherent MSCs (PA MSCs) and CD271+ MSC differentiation, as delineated by these measures, and no obvious differences in PA MSC and CD271+ MSC numbers, as depicted through cell confluence or pellet size; it will be important to normalise these differentiation outcome measures to confirmed cell numbers in future studies
Summary
Regenerative medicines using stem cells and/or tissue engineering approaches are expected to play a major role in the development of new healthcare in the 21st century, with much current interest and research activity. A major problem to this approach, especially if using autologous stem cells sourced from adult tissues remains in optimising which cells are best applied for different pathological conditions and tissues An example of this can be found in the development of treatment strategies for osteochondral defects, which is problematic as the damage extends to the subchondral bone and the repair responses demands the healing and reformation of two connective tissue types, i.e. cartilage and bone[1,2]. Www.nature.com/scientificreports use of MSCs for the repair of deep cartilaginous wounds highlights how there is a need to optimise adult stem cell-based therapies as well as identify potential mechanisms of action For this reason, much current interest in MSC-based regenerative medicines has been examining defined subpopulations of MSCs from the heterogeneous pools of cells present in bone marrow and different tissue sources[14,15,16,17]. We have examined the differentiation capacity and angiogenic activity of PA MSCs versus CD271+ MSCs in vitro
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