April 2020 HSC Section 4 - Plastic and Reconstructive Problems

The Journal of Craniofacial Surgery

Volume 30, Number 3, May 2019

Future of Facial Fat Grafting

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TABLE 1. Animal Studies of Fat Grafting Augmented with Stromal Vascular Fraction (SVF), and Ex vivo Expanded Adipose Stem Cells (ASCs) Study Experimental model Assessment methods Outcomes Reference Matsumoto et al, 2006 Human fat þ / labeled SVF implanted into immunodeficient mice Immunohistochemistry, immunofluorescence Labeled SVF cells found between adipocytes in connective tissue, some of which stained for Von Willebrand Factor Paik et al, 2015 Different doses of human-derived cells from SVF ranging from 10,000 to 10 million added to fat graft to immunodeficient mice Histology and volumetric analysis using CT SVF-enriched fat graft had improved volume retention compared to graft alone. Cell doses greater than 10,000 negatively impacted on volume retention. Zhu et al, 2015 Adipose tissue þ / SVF injected into nude mice Histology, immunohistochemistry, volumetric analysis Improved volume retention with greater vascularity on histology in SVF-enriched graft. SVF-enriched graft stained positively for hematogenous stem cell markers Zhou et al, 2015 Luciferase transgenic rat-derived adipose tissue injected þ / SVF into nude mice Volumetric analysis and immunohistochemistry Improved volume retention in SVF-enriched adipose. More structure and early vascularity with less necrosis cysts in SVF- enriched adipose Garza et al, 2015 Human ASC harvested after 1 passage, transfected with luciferase and implanted into nude mice Histology, bioluminescence imaging, flow cytometry and immunohistochemistry for angiogenic markers Considerable decrease in luminescence over 7 wks, angiogenesis in ASC-enriched grafts Zhang et al, 2015 ASC harvested from donor rats and passaged x4. Adipose grafts into recipient grafts þ / ASC apoptosis and increased vascularity in ASC-enriched grafts Piccinno et al, 2015 Autologous ASC passaged x4 and combined with autologous adipose grafting in rabbits. Adipose graft only as control Histology, immunohistochemistry, volumetric analysis Greater volume retention and vascularity in ASC-enriched grafts. Moseley et al, 2006 Transgenic donor mouse ASC separated by culture or as part of fresh SVF implanted along with adipose graft into athymic mice Histology, immunohistochemistry, volumetric analysis Greater volume retention in ASC-enriched graft, markers for Von Willebrand factor present in ASC-enriched grafts. transgenic stem cells confirmed at 6 months after engrafting Wang et al, 2018 Sprague-Dawley rats with critical-sized calvarial defects filled with polymer matrix seeded with ASC plus laser irradiation (n ¼ 6), unseeded polymer matrix plus laser irradiation, polymer matrix alone (n ¼ 6), and polymer matrix seeded with ASC (n ¼ 6) Successive radiologic analysis, histology, IHC for Von Willebrand factor, BMP2 and calcitonin ASC seeding with laser irradiation significantly increased bone regeneration compared to controls and matrix alone. ASC- seeding with irradiation was associated with greater staining for Von Willebrand factor Orbay et al, 2011 Lewis rats with critical-sized calvarial defects implanted with polymer matrix seeded with ASC (n ¼ 7), ASC-derived osteoblast (n ¼ 7), ASC- derived endothelial cells (n ¼ 7), no seeding (control) (n ¼ 9) Radiologic and histologic analysis Both micro-CT and H&E staining showed greatest mineral density bone regeneration in ASC-derived osteoblasts, Levi et al, 2010 Critical sized calvarial defect in mice with polymer matrix seeded with undifferentiated ASC (n ¼ 5), matrix alone (n ¼ 5), no matrix (control) (n ¼ 5) Dudas et al, 2006 New Zealand White rabbits with 8mm parietal defects. Treated with gelatin foam matrix seeded with ASC (n ¼ 9), osteoinduced ASC (n ¼ 7), gelatin foam matrix alone (n ¼ 6) autograft (n ¼ 6), no treatment (control) (n ¼ 6) Radiographical and histologic analysis Significantly greater healing in osteoinduced ASC compared to noninduced ASC. No improvement in healing compared to controls or gelfoam matrix alone Histology, volumetric analysis, immunohistochemistry Greater volume retention in ASC-enriched grafts. Reduced Radiologic and histologic analysis. IHC for COL1A1 and RUNX2 osteogenic markers. Quantitative PCR for osteogenic gene expression followed by ASC-derived endothelial cells. Unmodified ASC showed less mineral density than controls. Differences were nonsignificant Human ASC-treated defects showed extensive healing of compared to minimal healing in controls and unseeded matrix cohorts. Evidence of in vivo osteogenic differentiation

# 2019 Mutaz B. Habal, MD

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