Human Adipose Tissue Possesses a Unique Population of Pluripotent Stem Cells with Nontumorigenic and Low Telomerase Activities: Potential Implications in Regenerative Medicine

Abstract

In this study, we demonstrate that a small population of pluripotent stem cells, termed adipose multilineage-differentiating stress-enduring (adipose-Muse) cells, exist in adult human adipose tissue and adipose-derived mesenchymal stem cells (adipose-MSCs). They can be identified as cells positive for both MSC markers (CD105 and CD90) and human pluripotent stem cell marker SSEA-3. They intrinsically retain lineage plasticity and the ability to self-renew. They spontaneously generate cells representative of all three germ layers from a single cell and successfully differentiate into targeted cells by cytokine induction. Cells other than adipose-Muse cells exist in adipose-MSCs, however, do not exhibit these properties and are unable to cross the boundaries from mesodermal to ectodermal or endodermal lineages even under cytokine inductions. Importantly, adipose-Muse cells demonstrate low telomerase activity and transplants do not promote teratogenesis in vivo. When compared with bone marrow (BM)- and dermal-Muse cells, adipose-Muse cells have the tendency to exhibit higher expression in mesodermal lineage markers, while BM- and dermal-Muse cells were generally higher in those of ectodermal and endodermal lineages. Adipose-Muse cells distinguish themselves as both easily obtainable and versatile in their capacity for differentiation, while low telomerase activity and lack of teratoma formation make these cells a practical cell source for potential stem cell therapies. Further, they will promote the effectiveness of currently performed adipose-MSC transplantation, particularly for ectodermal and endodermal tissues where transplanted cells need to differentiate across the lineage from mesodermal to ectodermal or endodermal in order to replenish lost cells for tissue repair.

Mesenchymal Stem/Stromal Cells in Liver Fibrosis: Recent Findings, Old/New Caveats and Future Perspectives

“…1). Finally, by addressing previous questions and if the availability of certain cell sources of MSCs with the potential to differentiate in vivo into neural, mesodermal and hepatocyte-like cells is demonstrated, then the biology of subpopulations of pluripotent-like cells [43,44] able to generate MSCs will be better understood.…”

Mesenchymal Stem Cells as a Source of Schwann Cells: Their Anticipated Use in Peripheral Nerve Regeneration

“…Recently, pluripotent stem cells, named multilineagedifferentiating stress-enduring (Muse) cells, were discovered in MSCs such as BMSCs and ADSCs [Kuroda et al, 2010;Ogura et al, 2014]. Muse cells account for one to several percent of the total MSCs and, as is the case with MSCs, they are nontumorigenic and early realization of their application to regenerative medicine is highly anticipated.…”

“…They express pluripotency genes, such as Oct3/4, Nanog, Sox2, Rex1, are able to differentiate into mesodermal-, ectodermaland endodermal-lineage cells from a single cell and are self-renewable . The markers of each cell lineage into which Muse cells are able to differentiate are: ectodermal (nestin, NeuroD, Musashi, neurofilament, microtubule-associated protein-2, tyrosinase, microphthalmia-associated transcription factor, gf100, tyrosinase-related protein 1 and dopachrome tautomerase), mesodermal (brachyury, Nkx2.5, smooth muscle actin, osteocalcin, FABP-4 and desmin), and endodermal lineages (GATA-6, α-fetoprotein, cytokeratin-7 and albumin) [Kuroda et al, 2010;Wakao et al, 2011;Tsuchi- Ogura et al, 2014]. Expression of these markers is recognized under both spontaneous differentiation and cytokine induction systems.…”

Stem cell therapy in intracerebral hemorrhage rat model

“…Importantly, 0.6% of umbilical cord blood mononuclear cells are multipotent stress-enduring (Muse) cells. Muse cells are a non teratogenic pluripotent cell type that was recently isolated not only from UCB, but also from dermal fibroblasts, bone marrow, and adipose tissue [79,96,97] . important long lasting or permanent cognitive and motor impairments.…”