Abstract
IntroductionBone marrow (BM) stroma currently represents the most common and investigated source of mesenchymal progenitor cells (MPCs); however, comparable adult progenitor or stem cells have also been isolated from a wide variety of tissues. This study aims to assess the functional similarities of MPCs from different tissues and to identify specific factor(s) related to their multipotency.MethodsFor this purpose, we directly compared MPCs isolated from different adult tissues, including bone marrow, tonsil, muscle, and dental pulp. We first examined and compared proliferation rates, immunomodulatory properties, and multidifferentiation potential of these MPCs in vitro. Next, we specifically evaluated activin A expression profile and activin A:follistatin ratio in MPCs from the four sources.ResultsThe multidifferentiation potential of the MPCs is correlated with activin A level and/or the activin A:follistatin ratio. Interestingly, by siRNA-mediated activin A knockdown, activin A was shown to be required for the chondrogenic and osteogenic differentiation of MPCs. These findings strongly suggest that activin A has a pivotal differentiation-related role in the early stages of chondrogenesis and osteogenesis while inhibiting adipogenesis of MPCs.ConclusionsThis comparative analysis of MPCs from different tissue sources also identifies bone marrow-derived MPCs as the most potent MPCs in terms of multilineage differentiation and immunosuppression, two key requirements in cell-based regenerative medicine. In addition, this study implicates the significance of activin A as a functional marker of MPC identity.
Highlights
Bone marrow (BM) stroma currently represents the most common and investigated source of mesenchymal progenitor cells (MPCs); comparable adult progenitor or stem cells have been isolated from a wide variety of tissues
E transforming growth factor-β (TGF-β) superfamily of secreted factors includes TGF-β, activins, Nodal, and bone morphogenetic proteins (BMPs). e activation of the TGF-β/activin/Nodal signaling pathway through SMAD2/3 is associated with the pluripotency of human embryonic stem cells and is required for the maintenance of their undifferentiated state [18]. rough the induction of Oct4, Nanog, Nodal, Wnt3, basic fibroblast growth factor (FGF-2), and FGF-8, Activin A was shown to be a key regulator for the “stemness” maintenance of hESCs [19]
At day 21 of chondro genesis, alcian blue (AB) and picrosirius histologic staining of the chondrogenic pellets derived from BMMPCs, muscle-derived MPCs (M-MPCs), and dental pulp (DP)-MPCs all revealed the presence of a sulfated proteoglycan- and collagen-rich extracellular matrix
Summary
Bone marrow (BM) stroma currently represents the most common and investigated source of mesenchymal progenitor cells (MPCs); comparable adult progenitor or stem cells have been isolated from a wide variety of tissues. Mesenchymal progenitor cells (MPCs) are multipotent cells, derived from various adult tissues, that are capable of differentiating into several mesenchymal lineages, including osteoblasts, chondroblasts, and adipocytes. MPCs were initially identified and isolated from bone marrow (BM) and are characterized by the expression of a number of cell surface markers [3,4,5]. Based on their clonogenic and multipotent differentiation activities, to date, MPCs have been isolated from a number of adult tissues, including trabecular bone [6], fat [7,8],. Activin A is likely to have pleiotropic functions, including an essential role in sustaining hESC pluri potency, and to play a critical role during skeletogenesis
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