Abstract
Adipose-derived stem cells (ASCs) have been increasingly used as a versatile source of mesenchymal stem cells (MSCs) for diverse clinical investigations. However, their applications often become complicated due to heterogeneity arising from various factors. Cellular heterogeneity can occur due to: (i) nomenclature and criteria for definition; (ii) adipose tissue depots (e.g., subcutaneous fat, visceral fat) from which ASCs are isolated; (iii) donor and inter-subject variation (age, body mass index, gender, and disease state); (iv) species difference; and (v) study design (in vivo versus in vitro) and tools used (e.g., antibody isolation and culture conditions). There are also actual differences in resident cell types that exhibit ASC/MSC characteristics. Multilineage-differentiating stress-enduring (Muse) cells and dedifferentiated fat (DFAT) cells have been reported as an alternative or derivative source of ASCs for application in regenerative medicine. In this review, we discuss these factors that contribute to the heterogeneity of human ASCs in detail, and what should be taken into consideration for overcoming challenges associated with such heterogeneity in the clinical use of ASCs. Attempts to understand, define, and standardize cellular heterogeneity are important in supporting therapeutic strategies and regulatory considerations for the use of ASCs.
Highlights
Contrary to the embryonic stem cells found in the inner cell mass of blastocyst, postnatal stem cells or adult stem cells, such as mesenchymal stem cells (MSCs), can be found in almost all postnatal organs and tissues, most notably in bone marrow, White adipose tissue (WAT), amniotic fluid, dental tissues, blood, placenta, skin, synovial fluid, and Wharton’s jelly [7,8]
The first characterization of these cells, isolated from the human lipoaspirates, was reported about two decades ago in 2002 [9,10]. These adult stem cells, which Zuk et al named as processed lipoaspirate (PLA) cells, are adipose-derived stem cells (ASCs) that exhibit the properties of MSCs [9]
The first step in the isolation of ASCs from WAT involves the separation of adipocytes from the remaining adipose cells of the stromal vascular fraction (SVF) (Figure 1)
Summary
Adipose tissues play a pivotal physiological role in maintaining metabolic homeostasis in the body. White adipose tissue (WAT) stores excess energy in the form of triglyceride and is an endocrine organ that secretes adipokines. Adipocytes contain lipid droplets that store triglyceride, and they constitute approximately one third of the cells within adipose tissues [1]. S-WAT expands to store excess lipid, preventing ectopic lipid disposition and organ damage, while the main function of V-WAT is to cushion and protect the visceral organs [1,3]. Brown adipose tissue (BAT), found in the cervical–supraclavicular region of the neck, perirenal/adrenal and paravertebral regions in adult humans, and the interscapular region in rodents [4,5], plays a significant role in thermogenesis via the actions of uncoupling protein 1 (UCP1).
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