Isolation of CD248 Expressing Adipose Derived Stromal Cells for Targeted Improvement of Wound Healing
Elizabeth Brett, MS, Elizabeth Zielins, MD, Monica Chin, BS, Michael Januszyk, MD, Charles Blackshear, MD, Michael Findlay, MD, Cristhian Montenegro, MS, Dre Irizzary, MD, Dung Nguyen, MD, Geoffrey Gurtner, MD, Michael Longaker, MD, MBA, Derrick Wan, MD.
Stanford University, Palo Alto, CA, USA.
ISOLATION OF CD248-EXPRESSING ADIPOSE DERIVED STROMAL CELLS FOR TARGETED IMPROVEMENT OF WOUND HEALING
Elizabeth Brett1, MS; Elizabeth R. Zielins1, MD, Monica Chin1, BS, Michael Januszyk1, MD, , Charles P. Blackshear1, Michael Findlay1, MD, Cristhian Montenegro, MS1, Dre Irizzary, MD1, Dung Nguyen, MD1, Geoffrey C. Gurtner1, MD, Michael T. Longaker1, 2, MD, MBA, Derrick C. Wan1, MD
1Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Division of Plastic Surgery, Stanford University School of Medicine, Stanford, California, USA
2Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA
Wound healing remains a global issue of disability, cost, and health. Addition of cells from the stromal vascular fraction of adipose tissue have been shown to increase the rate and quality of dermal wound healing. The present study aimed to investigate the angiogenic mechanisms of CD248+ stromal vascular fraction cells in the context of full thickness excisional wounds.
Single cell transcriptional analysis was used to identify angiogenic gene-expressing ASCs, then correlate with surface marker expression. SVF cells isolated from human lipoaspirate were FACS sorted based on the presence of CD248. Cells were analyzed for gene expression of VEGF and HGF, and subsequently assessed for tubule formation in vitro. Following this, 6mm full thickness dermal wounds were created on the dorsa of immunocompromised mice, supplied with a pullalan-collagen hydrogel, and separated into 4 treatment groups; CD248+, CD248-, unsorted SVF, and hydrogel alone. Wounds were measured every other day photometrically until closure. Once fully healed, wounds were harvested for histological analysis through CD31 immunohistochemical staining.
Wounds treated with CD248+ cells healed significantly faster than the compared treatment groups. Moreover, immunohistochemistry of CD31 revealed a much higher presence of endothelial cells in the CD248+ group, indicating a large pro-angiogenic effect of CD248+ cells in vivo.
Therefore, using pro-angiogenic cells obtained from SVF presents a viable strategy in wound healing by proxy of increased vessel growth in the wound.
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