A Novel Porcine Model for Future Studies of Cell-enriched Fat Grafting

Rasmussen, Birthe Krogh; Sørensen, Celine Lykke; Vester-Glowinski, Peter; Herly, Mikkel; Kurbegovic, Sorel; Ørholt, Mathias; Svalgaard, Jesper Dyrendom; Kølle, Stig-Frederik Trojahn; Kristensen, Annemarie T.; Talman, Maj-Lis Møller; Drzewiecki, Krzysztof T.; Fischer‐Nielsen, Anne

doi:10.1097/gox.0000000000001735

Cited by 10 publications

(2 citation statements)

References 55 publications

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“…The phenotypic profile of ADSCs was determined by flow cytometry as previously described [24, 25]. Briefly, the cells were collected; stained with phycoerythrin (PE)-conjugated anti-CD11b, anti-CD19, anti-CD34, anti-CD45, anti-HLA-DR, anti-CD73, anti-CD90 and anti-CD105 antibodies (BD Bioscience, San Jose, CA); and analysed using an Epics Altra flow cytometer (Beckman Coulter, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Fat extract improves fat graft survival via proangiogenic, anti-apoptotic and pro-proliferative activities

Zheng

Deng

et al. 2019

Stem Cell Res Ther

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Background: Our previous study proved that nanofat could enhance fat graft survival by promoting neovascularization. Fat extract (FE), a cell-free component derived from nanofat, also possesses proangiogenic activity. Objectives: The aim of this study was to investigate whether FE could improve fat graft survival and whether FE and nanofat could work synergistically to promote fat graft survival. The underlying mechanism was also investigated. Methods: In the first animal study, human macrofat from lipoaspirate was co-transplanted into nude mice with FE or nanofat. The grafts were evaluated at 2, 4 and 12 weeks post-transplantation. In the second animal study, nude mice were transplanted with a mixture of macrofat and nanofat, followed by intra-graft injection of FE at days 1, 7, 14, 21 and 28 post-transplantation. The grafts were evaluated at 12 weeks post-transplantation. To detect the mechanism by which FE impacts graft survival, the proangiogenic, anti-apoptotic and pro-proliferative activities of FE were analysed in grafts in vivo and in cultured human vascular endothelial cells (HUVECs), adipose-derived stem cells (ADSCs) and fat tissue in vitro. Results: In the first animal study, the weights of the fat grafts in the nanofat-and FE-treated groups were significantly higher than those of the fat grafts in the control group. In addition, higher fat integrity, more viable adipocytes, more CD31-positive blood vessels, fewer apoptotic cells and more Ki67-positive proliferating cells were observed in the nanofat-and FE-treated groups. In the second animal study, the weights of the fat grafts in the nanofat+FE group were significantly higher than those of the fat grafts in the control group. In vitro, FE showed proangiogenic effects on HUVECs, anti-apoptotic effects on fat tissue cultured under hypoxic conditions and an ability to promote ADSC proliferation and maintain their multiple differentiation capacity. Conclusions: FE could improve fat graft survival via proangiogenic, anti-apoptotic and pro-proliferative effects on ADSCs. FE plus nanofat-assisted fat grafting is a new strategy that could potentially be used in clinical applications.

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Section: Methodsmentioning

confidence: 99%

Fat extract improves fat graft survival via proangiogenic, anti-apoptotic and pro-proliferative activities

Zheng

Deng

et al. 2019

Stem Cell Res Ther

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“…Early successful attempts at in vivo modeling of fat grafting were realized in rabbits and have recently been upscaled into pigs, [27][28][29][30][31][32][33][34] but these large animals cannot be used in the context of oncologic questions, as no leporine or porcine breast cancer models exist. [35][36][37][38] In fact, immunocompetent and orthotopically implanted breast cancer dormancy models have only been described in mice.…”

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confidence: 99%

Avascular fat grafts show lower volume retention but higher hypoxia, angiogenesis, adipocyte proliferation, and macrophage infiltration than vascularized adipocutaneous flaps in an in vivo pilot mouse study Fat grafting vs. flap transfer in mice

Thomas

Warszawski

Falkner

et al. 2023

Plastic &Amp; Reconstructive Surgery

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Background: Over 137,000 breast reconstructions are performed annually by American Society of Plastic Surgeons (ASPS) members. Vascularized flaps and avascular lipofilling each account for over 33,000 autologous reconstructions. Although clinical and experimental observations suggest biologic differences with diverging effects on locoregional tumor control, comparative animal models are lacking. The authors standardized existing techniques in immunocompetent mice, laying the foundation for in vivo models of autologous breast reconstruction combinable with orthotopic tumor implantations. Methods: Twenty-five groin flaps and 39 fat grafts were transferred in female BALB/c-mice. Adipocytes were tracked via Hoechst-Calcein-DiI staining (n = 2 per group), and postoperative volume retentions were compared via magnetic resonance imaging (n = 3 per group) on days 1, 11, 21, and 31. Proliferation indices, microvessel densities, tissue hypoxia, and macrophage infiltrates were compared via Ki67, CD31, pimonidazole, and hematoxylin-eosin staining on days 5, 10, 15, 20, and 30 (n = 4 per group). Results: Viable adipocytes were present in both groups. Graft volumes plateaued at 42.7 ± 1.2% versus 81.8 ± 4.0% of flaps (P < 0.001). Initially, grafts contained more hypoxic cells (day 5: 15.192 ± 1.249 versus 1.157 ± 192; P < 0.001), followed by higher proliferation (day 15: 25.2 ± 1.0% versus 0.0 ± 0.0%; P < 0.001), higher microvessel numbers (day 30: 307.0 ± 13.2 versus 178.0 ± 10.6; P < 0.001), and more pronounced macrophage infiltrates (graded 3 versus 2; P < 0.01). Conclusion: This comparative murine pilot study of vascularized flaps versus avascular lipofilling suggests differences in volume retention, proliferation, angiogenesis, hypoxia, and inflammation. Clinical Relevance Statement: The biological differences of fat grafting versus flap transfer are not fully understood because no single comparative experimental model has been established to date. The authors present the first comparative small animal model of both techniques, which will allow the gaining of deeper insights into their biological effects.

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