Alternative approaches to preserve MSC progenitor potency

which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Over the years, mesenchymal stem cells (MSCs) have gained increasing interest in various clinical fields due to its unique properties including immune modulation and tissue regeneration. The mechanisms by which MSCs exert its therapeutic potential can be broadly categorized into two groups: (1) stimulation of neighboring cells to facilitate repair by secretion of immunoregulatory, cell-mobilization, and growth factors and (2) direct replacement of damaged cells through multilineage differentiation. Despite high expectations on its success, the clinical outcomes of MSC therapy have been controversial with unclear efficacy [1]. Many studies now suggest that MSCs, itself, have inherent limitations due to its high immunoregulatory plasticity and significant degeneration in progenitor potency during culture expansion. As a transition, researchers are now reversely translating from clinical trials to pre-clinical research in order to overcome these limitations and to enhance the therapeutic functions of MSCs. Strategic approaches to overcome immu-noregulatory plasticity of MSCs have been previously discussed, which includes gene modification to intentionally over-express anti-inflammatory genes, pre-conditioning of MSCs with various cytokines or growth factors to allow MSCs to acquire immunoregulatory functions, and combined cell-based immune modulation to promote empowering and synergistic interactions between MSCs and immu-noregulatory cells [2-5]. Similarly, approaches to preserve and enhance progenitor potency of MSCs are being addressed. Proliferation, multilineage potential, and colony-forming efficiency are fundamental MSC progenitor properties that can improve the therapeutic potential for tissue repair and regeneration [6]. In this issue of Blood Research, Bae et al. [6] suggest that three dimensional (3D) culture system could promote the osteogenic and adipogenic differentiation potential of bone-marrow derived mouse MSCs, and additional treatment of azacitidine (AZA), a DNA methyltransferase inhibitor, could further enhance the osteogenic differentiation ability. However, other progenitor properties, including proliferation and colony-forming efficiency were not significantly affected by either treatment compared to conventionally cultured MSCs. Bone-marrow derived MSCs reside within a complex environment in which MSCs are subjected to various mechanical stimuli of the bone and also environmental stimuli from interacting cell types. However, classic two dimensional (2D) cultures lack these mechanical stimuli and vital cues by hematopoietic cells and nonadherent population of mesenchymal progenitors. Therefore, to preserve MSC progenitor potency, studies have focused on expansion techniques to recreate an elaborate bone marrow niche through 3D expansion, hypoxia, and growth factors [7]. 3D expansion cultures of MSCs can be …