Fat tissue: an underappreciated source of stem cells for biotechnology

Adipose tissue can be harvested in large amounts with minimal morbidity. It contains numerous cells types, including adipocytes, preadipocytes, vascular endothelial cells and vascular smooth muscle cells; it also contains cells that have the ability to differentiate into several lineages, such as fat, bone, cartilage, skeletal, smooth, and cardiac muscle, endothelium, hematopoietic cells, hepatocytes and neuronal cells. Cloning studies have shown that some adipose-derived stem cells (ADSCs) have multilineage differentiation potential. ADSCs are also capable of expressing multiple growth factors, including vascular endothelial growth factor and hepatocyte growth factor. Early, uncontrolled, non-randomized clinical research, applying fresh adipose-derived cells into a cranial defect or undifferentiated ADSCs into fistulas in Crohn's disease, has shown healing and an absence of side effects. The combination of these properties, and the large quantity of cells that can be obtained from fat, suggests that this tissue will be a useful tool in biotechnology.

Introduction

Adipose tissue has a remarkable ability to undergo considerable changes in volume during the lifespan of an individual. Although relatively small increases in volume can be accommodated by changes in the amount of lipid stored in individual adipocytes (hypertrophy), larger changes are mediated by the generation of new adipocytes (hyperplasia) accompanied by coordinated expansion and remodeling of the adipose vasculature 1, 2. These changes are mediated by a population (or populations) of stem and progenitor cells within adipose tissue. Thus, for many years researchers studied the adipogenic potential of preadipocytes within the stromal vascular fraction of adipose tissue 3, 4, 5. Subsequently, we, and others, have shown that in addition to committed adipogenic and vascular cells, such as smooth muscle cells and endothelium, adipose tissue contains a multipotent cell population with properties that are similar, although not identical, to those of marrow-derived mesenchymal stem cells (MSCs) 6, 7, 8, 9, 10, 11: we refer to these cells as adipose-derived stem cells (ADSCs). Other names used in the literature for multipotent cells derived from adipose tissue include adipose-derived adult stem cells (ADAS), human multipotent adipose-derived stem cells (hMADS), processed lipoaspirate cells (PLA) and adipose tissue-derived stromal cells. In addition, Folkman et al. showed that the vascular plasticity of adipose tissue derives from the maintenance of microvascular endothelial cells (and their progenitors) in a relatively immature state [1] – a finding that is consistent with the presence of endothelial progenitor cells within adipose tissue [12]. In this review we discuss the biology of these stem and progenitor cell populations and examine the potential role of adipose tissue as a source of cells for biotechnology and, in particular, for regenerative medicine.