Mesenchymal stem cells from the outer ear: a novel adult stem cell model system for the study of adipogenesis

Abstract

Adipocytes arise from multipotent stem cells of mesodermal origin, which also give rise to the muscle, bone, and cartilage lineages. However, signals and early molecular events that commit multipotent stem cells into the adipocyte lineage are not well established mainly due to lack of an adequate model system. We have identified a novel source of adult stem cells from the external murine ears referred to here as an ear mesenchymal stem cells (EMSC). EMSC have been isolated from several standard and mutant strains of mice. They are self-renewing, clonogenic, and multipotent, since they give rise to osteocytes, chondrocytes, and adipocytes. The in vitro characterization of EMSC indicates very facile adipogenic differentiation. Morphological, histochemical, and molecular analysis after the induction of differentiation showed that EMSC maintain adipogenic potentials up to fifth passage. A comparison of EMSC to the stromal-vascular (S-V) fraction of fat depots, under identical culture conditions (isobutyl-methylxanthine, dexamethasone, and insulin), revealed much more robust and consistent adipogenesis in EMSC than in the S-V fraction. In summary, we show that EMSC can provide a novel, easily obtainable, primary culture model for the study of adipogenesis.

Artificial Sweeteners Stimulate Adipogenesis and Suppress Lipolysis Independently of Sweet Taste Receptors

“…We then examined sweet taste receptor expression in primary eMSCs as an independent adipogenic model. These cells are isolated from the mouse ear and are capable of chondrogenic, osteogenic, and adipogenic differentiation (29). We found that sweet taste receptor expression in this system was reminiscent of that in 3T3-L1 cells; T1R2 and T1R3 both peaked in expression at day 2 of adipogenesis before returning to preadipocyte levels at day 12 ( Fig.…”

“…eMSC Isolation-eMSCs were isolated from controls, T1R2 KO, T1R3 KO, and T1R2/T1R3 double KO mice as described previously (29). Briefly, mouse ears were sterilized, minced, and incubated for 1 h in collagenase to obtain a cell suspension.…”

“…Human SVC Isolation-SVCs were isolated from a subcutaneous fat depot of a 54-year-old diabetic patient in the same manner as eMSCs (29). Human SVCs were maintained and differentiated in the same manner as eMSCs.…”

Secreted frizzled-related protein 5 suppresses adipocyte mitochondrial metabolism through WNT inhibition

“…We found that Sfrp5 mRNA was induced with differentiation of 3T3-L1 preadipocytes (Supplemental Figure 1A; supplemental material available online with this article; doi:10.1172/JCI63604DS1) and with adipogenesis of ear mesenchymal stem cells (EMSCs) (36) isolated from the outer ears of mice ( Figure 1A). Consistent with Sfrp5 induction during preadipocyte differentiation, and in agreement with previous studies (31,32,34), expression of Sfrp5 mRNA was markedly higher in the adipocyte fraction than in the stromal-vascular fraction of WAT from lean mice ( Figure 1B).…”

Reprogramming mouse ear mesenchymal stem cells (EMSC) expressing the Dlk1-Dio3 imprinted gene cluster

“…EMSC also serve as a simple model for adipogenesis [20] with potentially broader applications for regenerative medicine [21]. Human mesenchymal stem cells (MSCs) are also capable of undergoing adipogenesis; a process that is in part, regulated by the delta-like 1 (Dlk-1) gene [22].…”