Program in Molecular Medicine; Department of Surgery; School of Medicine; Senior Scholars Program
Janice Lalikos, MD
Medical Education | Molecular, Cellular, and Tissue Engineering | Plastic Surgery | Surgical Procedures, Operative | Therapeutics | Tissues
Adipose tissue (AT) is used extensively in reconstructive and regenerative therapies, but transplanted fat often undergoes cell death, leading to inflammation, calcification, and requirement for further revision surgery. Previously, we have found that mesenchymal progenitor cells within human AT can proliferate in three-dimensional culture under proangiogenic conditions. These cells (primed ADipose progenitor cells, PADS) robustly differentiate into adipocytes in vitro (ad-PADS). The goal of this study is to determine whether ad-PADS can form structured AT in vivo, with potential for use in surgical applications. Grafts formed from ad-PADS were compared to grafts formed from AT obtained by liposuction after implantation into nude mice. Graft volume was measured by microcomputed tomography scanning, and the functionality of cells within the graft was assessed by quantifying circulating human adiponectin. The degree of graft vascularization by donor or host vessels and the content of human or mouse adipocytes within the graft were measured using species-specific endothelial and adipocyte-specific quantitative real time polymerase chain reaction probes, and histochemistry with mouse and human-specific lectins. Our results show that ad-PADS grafted subcutaneously into nude mice induce robust vascularization from the host, continue to increase in volume over time, express the human adipocyte marker PLIN1 at levels comparable to human AT, and secrete increasing amounts of human adiponectin into the mouse circulation. In contrast, grafts composed of AT fragments obtained by liposuction become less vascularized, develop regions of calcification and decreased content of PLIN1, and secrete lower amounts of adiponectin per unit volume. Enrichment of liposuction tissue with ad-PADS improves vascularization, indicating that ad-PADS may be proangiogenic. Mechanistically, ad-PADS express an extracellular matrix gene signature that includes elements previously associated with small vessel development (COL4A1). Thus, through the formation of a proangiogenic environment, ad-PADS can form functional AT with capacity for long-term survival, and can potentially be used to improve outcomes in reconstructive and regenerative medicine.
adipocytes, adipogenesis, adipose tissue, extracellular matrix, mice, nude, regenerative medicine, stem cells
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Copyright © Raziel Rojas-Rodriguez et al., 2019; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are cited.
DOI of Published Version
Tissue Eng Part A. 2019 Jun;25(11-12):842-854. doi: 10.1089/ten.TEA.2018.0067. Epub 2019 Jan 4. Link to article on publisher's site
Tissue engineering. Part A
Rojas-Rodriguez, Raziel; Lujan-Hernandez, Jorge; Min, So Yun; DeSouza, Tiffany; Teebagy, Patrick; Desai, Anand; Tessier, Heather; Slamin, Robert; Siegel-Reamer, Leah; Berg, Cara; Baez, Angel; Lalikos, Janice F.; and Corvera, Silvia, "Generation of Functional Human Adipose Tissue in Mice from Primed Progenitor Cells" (2019). University of Massachusetts Medical School. Senior Scholars Program. Paper 277.
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This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License