Insulin-Like Growth Factor-I Stimulates Both Cell Growth and Lipogenesis during Differentiation of Human Mesenchymal Stem Cells into Adipocytes

Abstract

Insulin is known to regulate adipocyte differentiation and lipid accumulation, but the specific mechanism by which precursor cells differentiate into adipocytes is not clearly understood. This study evaluated the role of the IGF-I receptor in the process of adipocyte differentiation in bone marrow-derived human mesenchymal stem cells (HMSCs). The results demonstrated that nanomolar concentrations of IGF-I adequately replaced micromolar concentrations of insulin in supporting differentiation and lipid accumulation in HMSCs. The addition of IGF-I specifically increased cell proliferation and lipid accumulation in HMSCs, but a mixture of differentiation factors including dexamethasone, indomethacin, and 3-isobutyl-1-methylxanthine did not. These effects were blocked by the alphaIR-3 antibody, which inhibits IGF-I receptor activity. We also describe the pattern of differentiation with regard to cell growth, lipid accumulation, and morphologic changes and define the changes in these parameters that are influenced by IGF-I. Finally, peroxisome proliferator activating receptor-gamma immunoreactivity was also increased in response to IGF-I, and this effect was blocked in cells treated with the alphaIR-3 antibody. Taken together, these findings suggest that IGF-I plays a critical role in adipocyte differentiation and lipid accumulation.

Insulin‐like growth factor 1 has multisystem effects on foetal and preterm infant development

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Suppression of PDGF-induced PI3 kinase activity by imatinib promotes adipogenesis and adiponectin secretion

“…Important distinctions that may account for our findings relate to the intrinsic responsiveness of hMSCs to insulin signalling and to the nature of the proadipogenic stimuli used in our study. Unlike mouse 3T3-L1 cells, hMSCs do not differentiate into adipocytes in response to insulin or insulin-like growth factor 1 (IGF1) alone, instead requiring glucocorticoid to prime the cells to be responsive to pro-adipogenic stimuli (Greenberger 1979, Scavo et al 2004. In light of this, we have used a differentiation media solely consisting of physiological levels of glucocorticoid to enable us to measure adipogenic responses in the absence of other known pro-adipogenic stimuli including insulin and IGF1.…”

A Nonhuman Primate Model for Urinary Bladder Regeneration Using Autologous Sources of Bone Marrow-Derived Mesenchymal Stem Cells

“…bMSCs were subjected to coerced differentiation into an adipocyte lineage using a protocol for human MSC differentiation [21]. bMSCs were plated at 2,500 cells/cm 2 and grew for approximately 10 days in MSCGM until reaching 100% confluency.…”

“…bMSCs underwent three cycles of an induction/maintenance regimen in which MSCs were cultured in adipogenic induction media (Lonza, Inc.) for 3 days followed by 3 days of maintenance in adipogenic maintenance media. Induced bMSCs were stained with Oil Red O (Milipore Corporation, Temecula, CA) to visualize adipocytes by an established protocol [21]. Guidelines for the animal research protocols were established and approved by the Animal Care Committee at the University of Illinois at Chicago.…”