**Abbreviations**

numerous paracrine factors, including VEGF, and inducing endothelial differentiation and vessel formation, the question of whether the ASC plays a role in this vascular pathology should be asked. The fragile capillaries allow the filtration of protein-rich plasma into the interstitial space, driving the formation of edema [255]. In the early stages of LD, lymphatic drainage can keep up [260]. However with progression of the disorder, lymphatic drainage does decrease as the patient ages [253]. Added to this, the hypertrophic adipocytes are thought to physically restrict fluid drainage and the smaller lymphatic vessels themselves are thought to become "leaky", possibly through the appearance of microaneurysms in these vessels [253]. All of this results in the accumulation of lymph within the adipose tissue. Recent studies now suggest that "lymph can make you fat" [261]. In support of this, adipogenesis in vitro increases

(e.g. macrophage infiltration) are also likely to be involved. Paracrine activity is shown as solid arrows.

68 Regenerative Medicine and Tissue Engineering

**Figure 2.** Lipedema. Development of lipedema may have numerous commonalities with obesity starting with the de‐ velopment of hypertrophic adipocytes. Howerver, causation for this is unknown at this time may involve the ASC. As with obesity, adipocyte hypertrophy can lead to the development of hypoxia and the release of inflammatory cyto‐ kines from the adipocyte. Possible release of these factors from the ASC due to hypoxia is also shown. In addition, adipocyte hypertrophy is also accompanied by the development of "leaky" capillaries and lymphatics. While the cause of pathologic angiogenesis remains unclear, a role for the gene Prox-1 is though to be involved in lymphatic patholo‐ gy. Increased filtration from capillaries, combined with poor lypmphatic drainage (due to hypertrophic adipocytes and the the leaking of lymph back from the lymphatic vessel) leads to an accumulation of protein rich fluids within the tissue. Fluid accumulation and hypoxia may induce pro-inflammatory cytokine release. Other mechanisms of obesity

> ASC = adipose-derived stem cell; EC = endothelial cell; LD = lipedema; MSC = mesenchymal stem cell; GFAP = glial fibrillary acidic protein; HLA = human leukocyte antigen; IR = ischemia

reperfusion; LVEF = left ventricular ejection fraction; MAP2 = microtubule associated pro‐ tein-2; MLR = mixed lymphocyte reaction; PLA = processed lipoaspirate; RAD = rare adipose disorder; SVF = stromal vascular fraction; SC = Schwann cell; Tuj-1 = class III beta-tubulin; vWF = von Willebrand factor
