Coculture of Endothelial Cells and Mature Adipocytes Actively Promotes Immature Preadipocyte Development In Vitro.

Abstract

ABSTRACT. Adipose tissue consists of mature adipocytes and endothelial cells, which are all supported by the extracellular matrix. Adipose tissue development is closely associated with angiogenesis. However, the adipocyteendothelial cell interaction is unclear. To address this issue, we examined the effects of endothelial cells on the growth, apoptosis, and differentiation of mature adipocytes in three-dimensional collagen gel culture of the adipocytes with or without rat lung endothelial (RLE) cells. Spindle-shaped preadipocytes, an immature type of adipocyte, developed more actively around the adhesion sites of RLE cells to mature adipocytes in the coculture (rate of preadipocytes: 18.9±4.3%) than in the culture of adipocytes alone (2.0±5.1%). With respect to growth, RLE cells induced about a three-fold increase in bromodeoxyuridine uptake of mature adipocytes alone, while RLE cells did not influence the uptake of preadipocytes. RLE cells also did not affect the apoptotic indices by immunohistochemistry for single-stranded DNA in mature adipocytes or preadipocytes. These phenomena were not reproduced by RLE cell-conditioned medium, or by certain endothelial cell-produced cytokines. Our in vitro study is the first demonstration that endothelial RLE cells promote the active development of preadipocytes together with increased growth of mature adipocytes. These results suggest that endothelial cells are involved in the enlargement mechanism of adipose tissue mass through their direct adhesion to mature adipocytes.

Paracrine Regulation of Angiogenesis and Adipocyte Differentiation During In Vivo Adipogenesis

“…Angiogenesis precedes the development 16,50,51 and repair 52 of organs. Secreted factors from vascular endothelial cells induce proliferation and differentiation of preadipocytes, [53][54][55] liver organogenesis, 50 pancreas differentiation, 56 and liver protection. 57 VEGF is a critical factor in both pathological and physiological angiogenesis.…”

Adipose-Derived Stem Cells for Regenerative Medicine

“…109 Further support for a paracrine relationship between these lineages comes from the observation of increased proliferative rates noted in 2D and 3D cocultures of preadipocytes and endothelial cells. 64,110 Smooth Muscle In vitro, human ASCs can express ␣-smooth muscle actin, calponin, and SM22, consistent with a smooth muscle phenotype. 111,112 The addition of transforming growth factor-␤ and sphingosylphosphorylcholine induces human ASC expression of smooth muscle-associated markers.…”

Plasticity of Human Adipose Lineage Cells Toward Endothelial Cells

“…To address this issue, we used another approach previously described to obtain a homogeneous population of adipocyte precursor cells from adipose tissue. [22][23][24] We isolated human mature adipocytes from tissue, obtaining a Ͼ99% pure floating population of cells. When cultured under the described conditions, adipocytes first lost their fatty acids and changed their morphology to a preadipocyte-like then to a fibroblast-like type of cell that could attach to the coverslip.…”