Human adipose-derived stromal vascular fraction: characterization, safety and therapeutic potential in an experimental mouse model of articular injury

• Type of Material: Article
• Authors: Jordan A Dykstra, University of South Dakota; Elliot D Blue, University of South Dakota; Pedro L Negrao de Assis, Sanford Research, Sioux Falls; Jill M Weimer, University of South Dakota; Daniel J Kota, Emory University
• Language: English
• Date: 2020-05-27
• Publisher: German Stem Cell Society
• Publication Version: Final Published Version
• Copyright Statement: © Journal of Stem Cells and Regenerative Medicine
• Final Published Version (URL): http://dx.doi.org/10.46582/jsrm.1601004
• Title of Journal or Parent Work: Journal of Stem Cells and Regenerative Medicine
• Volume: 16
• Issue: 1
• Start Page: 16
• End Page: 25
• Grant/Funding Information: This work was supported by a grant from the National Institutes of Health to J.M.W. (R01NS082283). This work also received support from the Histology and Imaging Core within the Sanford Research Center for Pediatric Research (NIH P20GM103620), and the Flow Cytometry Core within the Sanford Research Center for Cancer Biology (NIH P20GM103548).
• Keywords: Mesenchymal stem cell; Autologous stem cells; Cartilage; Adipose
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Due to their capacity to self-renew, proliferate and generate multi-lineage cells, adult-derived stem cells offer great potential in regenerative therapies to treat maladies such as diabetes, cardiac disease, neurological disorders and orthopedic injuries. Commonly derived from adipose tissue, the stromal vascular fraction (SVF), a heterogeneous cell population enriched with mesenchymal stem cells (MSCs), has garnered interest as a cellular therapy due to ease of accessibility as an autologous, point-of-care application. However, the heterogeneous cell population within SVF is not historically taken into consideration when injecting into patients. Here, we characterized SVF, determined its safety and verify its therapeutic effects in a NOD/scid mouse model of articular injury. SVF were isolated from lipoaspirates utilizing a commercially available system (InGeneron Inc.), while MSCs were isolated from SVF via cell culture. Flow cytometry showed that neither age nor BMI affects the frequency of progenitor cells-like (CD31+CD34+), immune cells-like (CD4+) T cells, (CD14+) monocytes and total number of cells obtained. However, there was a negative correlation between donor BMI and MSC frequency within the SVF. ELISAs showed that following LPS activation in SVF, there were low levels of TNF-α and high levels of IL-10 secreted. However, T cell activation with anti-CD3 or anti-CD3+ anti-CD28, while leading to expected high levels of IFN-γ, did not lead to significant levels of TGF-β. PCR analysis showed no significant numbers of cells outside the joint 1-hour post injection, moreover, no engraftment or abnormal growth in other organs 60-days post injection. Finally, both cell populations were able to ameliorate disease progression, as confirmed by the increase in movement of treated groups compared to injured groups. Noteworthy, the histological analysis indicated that there was no cartilage growth, suggesting an alternative therapeutic mechanism to cartilage regeneration.