Adipose Stromal Cells Contain Phenotypically Distinct Adipogenic Progenitors Derived from Neural Crest

Abstract

Recent studies have shown that adipose-derived stromal/stem cells (ASCs) contain phenotypically and functionally heterogeneous subpopulations of cells, but their developmental origin and their relative differentiation potential remain elusive. In the present study, we aimed at investigating how and to what extent the neural crest contributes to ASCs using Cre-loxP-mediated fate mapping. ASCs harvested from subcutaneous fat depots of either adult P0-Cre/or Wnt1-Cre/Floxed-reporter mice contained a few neural crest-derived ASCs (NCDASCs). This subpopulation of cells was successfully expanded in vitro under standard culture conditions and their growth rate was comparable to non-neural crest derivatives. Although NCDASCs were positive for several mesenchymal stem cell markers as non-neural crest derivatives, they exhibited a unique bipolar or multipolar morphology with higher expression of markers for both neural crest progenitors (p75NTR, Nestin, and Sox2) and preadipocytes (CD24, CD34, S100, Pref-1, GATA2, and C/EBP-delta). NCDASCs were able to differentiate into adipocytes with high efficiency but their osteogenic and chondrogenic potential was markedly attenuated, indicating their commitment to adipogenesis. In vivo, a very small proportion of adipocytes were originated from the neural crest. In addition, p75NTR-positive neural crest-derived cells were identified along the vessels within the subcutaneous adipose tissue, but they were negative for mural and endothelial markers. These results demonstrate that ASCs contain neural crest-derived adipocyte-restricted progenitors whose phenotype is distinct from that of non-neural crest derivatives.

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

“…neuronal cells) have been induced from MSCs , mostly by cytokine stimulation and/ or gene introduction [Makino et al, 1999;Pittenger et al, 1999;Spees et al, 2003;Dezawa et al, 2004;Dezawa et al, 2005;Oyagi et al, 2006]. Furthermore, several studies have indicated that some adult bone marrowderived MSCs (BMSCs) and adipose-derived stem cells (ADSCs) are derived from the neural crest, an ectodermal lineage, which might provide an explanation for the ability of MSCs to generate Schwann cells [Billon et al, 2007;Takashima et al, 2007;Nagoshi et al, 2008;Sowa et al, 2013]. These findings indicate that Schwann cells, which belong to the ectodermal lineage, could also be induced from MSCs.…”

Craniomaxillofacial Sources of Mesenchymal Stem Cells: A Brief Review

“…Neural crest-derived adipose stem cells (NCDASC) are technically a subpopulation within ASC, showing similar MSC markers as their non-neural crest derived counterparts, but demonstrate a multipolar morphology for neural crest progenitors (i.e. Nestin and Sox2) as well as preadipocytes (CD24, CD34, S100) [75,76] . However, while NCDASC maintain their predilection towards an adipogenic lineage, they show reduced osteogenic and chondrogenic potential [75] .…”

“…Nestin and Sox2) as well as preadipocytes (CD24, CD34, S100) [75,76] . However, while NCDASC maintain their predilection towards an adipogenic lineage, they show reduced osteogenic and chondrogenic potential [75] . Another group also confirmed that a subset of adipocytes originate from the neural crest; as well, the neural-crest derived subpopulation under the proper stimulation will differentiate into adipocytes [77] .…”

Heterogeneity of Progenitor Cell Populations and their Therapeutic Implications

“…Similar to the differences seen in the osteogenic potential of neural crest vs. mesoderm-derived calvarial bones, the developmental origin of ASCs may contribute to their adipogenic ability. Sowa et al found that, albeit small, the subpopulation of ASCs derived from the neural crest is phenotypically unique from non-neural crest derived ASCs, and restricted primarily to adipogenic differentiation [61]. [64].…”