Ultrastructural assessment of cellulite morphology: clues to a therapeutic strategy?

Abstract

Introduction and aims: Cellulite is a problematic condition affecting mostly women, characterized by a bumpy or nodular skin surface. Recent approaches with laser treatment have offered some promise. The present study sought to identify possible targets for laser treatment or light therapy through an ultrastructural investigation of the condition.

Subjects and methods: Study subjects comprised 7 healthy Japanese female volunteers (Age range 37-46 yr, average 38.4) with cellulite, graded on the 4-point Nurnberger-Muller cellulite severity scale. Four patients were at grade 2 and 3 at grade 3. Three millimeter punch biopsies were obtained and routinely processed for light and transmission electron microscopy.

Results: Microphotography of specimens from cellulite patients demonstrated the presence of fibrotic septa which divided up larger clusters of adipose tissue into smaller packets, with the septa acting as a tethering system, thus producing the typical dimpling pattern. Ultrastructural findings showed proliferation of collagen and elastic fibers down into the cellulite tissue with compression of capillaries and congestion of arterioles, resulting in poor blood flow.

Conclusions: The histological and ultrastructural findings of cellulite clearly distinguish the condition from simple fat deposition. The remodeling of the fat layer into lobulated packets of lipocytes sequestered by fibrotic septa with a high proportion of elastic fibers would suggest the use of a fiber-based interstitial laser-assisted lipolysis system at an appropriate wavelength which might offer benefits through disruption of the septae through a photomechanical effect and lipolysis of the sequestered lipocytes. This could be followed by a course of near-infrared phototherapy to accelerate clearance of freed lipid and debris and reestablish the vascular system.

Figure 1:

A view of Grade 2 cellulite on the Nurnberger-Muller scale. The cellulite in this patients was diagnosed as Grade 3 on account of the modest bumpiness of the skin surface visible on the pinch test and while standing. The skin surface presents the typical ‘orange peel appearance’ characteristic of cellulite.

Figure 2:

Histology of normal fat layer (upper panel) and cellulite skin region (lower panel) In the upper photomicrograph, the adipose tissue presents as large clusters with surrounding coarse connective tissue. The lower photomicrograph of a skin section from a cellulite region shows that the large clusters of adipose tissue are sequestered by septa of connective tissue to form small clusters. Those clusters are closely linked to connective tissue in the periphery of the adipose tissue, where a number of lipid droplets that have proliferated are noted (arrow). (Toluidine blue stain, light microscopy, scale bars as shown)

Figure 3:

Cellulite skin region. This photomicrograph of a skin region shows proliferation of small lipid droplets (L) which can be seen synthesized in an adipocyte (A), and hemostasis in the capillary lumen (Cap) are noted. Proliferation of collagen fibers (Co) and elastic fibers (arrow) are also evident in this region. (Transmission electron microscopy with double staining using oolong tea extract for connective tissue: Scale bar as shown)

Figure 4:

Cellulite skin region. A capillary (Cap) with narrowing of the lumen due to fat cell compression and congestion of an arteriole (Ar) are noted in the periphery of the adipose tissue . (Upper panel): L: lipid droplet, Co: collagen fibril. Collagen fibers and fibroblasts (FB) are found on the surface of an adipocyte (A) possessing a large lipid droplet (L). (Lower panel): Capillary (Cap) endothelial cells presenting a practically normal picture and those having vacuolar degeneration are noted. (Transmission electron microscopy with double staining using oolong tea extract for connective tissue: Scale bar as shown)

Figure 5:

Histogenesis of cellulite. As regards the pathophysiological genesis of cellulite, it is considered that cellulite represents a condition in which fibrosis arises with the proliferation of fibroblasts around adipose cells (center) in association with progressing peripheral circulatory failure and metabolic failure in normal tissue (left), thereby leading to progressively enhancing metabolic failure in adipose tissue (center) and eventually to adipose tissue degeneration and advanced fibrosis in the surrounding tissues (right).