Abstract
BackgroundMesenchymal stem cells (MSCs) isolated from adult tissues (Ad-MSCs) have shown great promise for use in regenerative medicine. However, their poor in vitro expansion capacity and tissue scarcity have been major limitations. In this study, we demonstrate that mouse embryonic stem cells (mESCs) can differentiate into cells with MSC properties.MethodsUsing previously established methods that characterize Ad-MSCs, we analyzed mESC-differentiated fibroblasts (mESC-FBs), including plastic adherence, clonogenic growth, MSC marker expression, tri-lineage differentiation potential, and the capacity to express immunomodulators.ResultsAlthough previously characterized as mESC-differentiated fibroblasts (mESC-FBs), these cells exhibit major properties of Ad-MSCs. However, mESC-FBs also display unique features inherited from ESCs, including robust expansion capacity, senescence resistance, and attenuated innate immunity. In particular, mESC-FBs are insensitive to bacterial endotoxin (lipopolysaccharide, LPS) and do not express LPS-induced inflammatory molecules, in contrast to bone marrow (BM)-MSCs. We further demonstrate that mESC-FBs are resistant to the cytotoxicity associated with inflammatory cytokines, bacterial endotoxins (LPS and heat-killed bacteria), and macrophage-mediated inflammation.ConclusionsWhile it remains to be determined how the unique properties of mESC-FBs will affect their immunoregulatory activity under an in vivo condition, our findings demonstrate that ESCs could be used as an alternative source to generate a new class of ESC-MSCs with unique features potentially useful in regenerative medicine.
Highlights
Mesenchymal stem cells (MSCs) isolated from adult tissues (Ad-MSCs) have shown great promise for use in regenerative medicine
Together with similar results found in other types of Embryonic stem cell (ESC)-DCs [12,13,14,15,16], our findings demonstrated that innate immunity is developmentally regulated, but the commonly used in vitro differentiation methods can only partially promote this development
In addition to the complete loss of ESC morphology, the expression level of the pluripotency marker genes Oct4, Nanog, and Sox2 in mouse ESC (mESC)-FBs is less than 1% of that expressed in mESCs
Summary
Mesenchymal stem cells (MSCs) isolated from adult tissues (Ad-MSCs) have shown great promise for use in regenerative medicine. Their poor in vitro expansion capacity and tissue scarcity have been major limitations. Mesenchymal stem cells (MSCs) isolated from adult tissues (Ad-MSCs) have rapidly advanced to clinical application due to their defined differentiation potential (typically to osteocytes, chondrocytes, and adipocytes) and their ability to secrete immunomodulators and trophic growth factors that repress inflammation and promote tissue regeneration in the host [1,2,3]. Together with similar results found in other types of ESC-DCs [12,13,14,15,16], our findings demonstrated that innate immunity is developmentally regulated, but the commonly used in vitro differentiation methods can only partially promote this development
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