Adipose Tissue: Understanding the Heterogeneity of Stem Cells for Regenerative Medicine

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.

Secretome effect of adipose tissue-derived stem cells cultured two-dimensionally and three-dimensionally in mice with streptozocin induced type 1 diabetes

“…One of them would be the expression of CD105 + in more than 95% of the cultivated cell population ( Dominiciet al., 2006 ). However, when the cultivated stem cell is derived from adipose tissue, there are different reports in the literature and a consensus has not yet been observed ( Ong et al., 2021 ). When analyzing the SVF of adipose tissue which was recently isolated, a lower CD105 + cells percentage is observed.…”

Regulatory Role of Mesenchymal Stem Cells on Secondary Inflammation in Spinal Cord Injury

“… 21 The International Society for Cellular Therapy sets a minimum standard of MSCs as follows: cells that are positive for the surface markers of cluster of differentiation (CD)73, CD90, CD29, and CD105, but not with CD14, CD45, CD34, CD11b, or human leukocyte antigen-DR; are plastic-adherent and fibroblast-like under standard culture conditions; and can differentiate into chondrocytes, adipocytes and osteoblasts in vitro. 22 Due to the low expression of costimulatory molecules and class II major histocompatibility complex, these pluripotent stem cells do not trigger an obvious immune response after transplantation. 22 , 23 To date, MSCs have been isolated from distinct adult tissues (eg, bone marrow, peripheral blood, adipose tissue) and neonatal tissues (eg, umbilical cord and placenta).…”

Recent Advances in Translational Adipose-Derived Stem Cell Biology

“…In their comprehensive review, Ong et al discussed the heterogeneity of human ACSs, which can potentially represent an obstacle in the translation of basic ACS research into the clinics [5]. Among other factors, the source of ASCs (e.g., subcutaneous vs. visceral fat), donor and inter-subject variations as well as details of the study design were identified as potential hurdles for translational use of ASCs.…”