Optimization and Standardization of the Immunodeficient Mouse Model for Assessing Fat Grafting Outcomes

Kokai, Lauren; Jones, Taraneh; Silowash, Russell; Theisen, Brian; DiBernardo, Gabriella; Lu, Andrew; Yi, Baolian; Marra, Kacey G.; Rubin, J. Peter

doi:10.1097/prs.0000000000003868

Cited by 14 publications

(3 citation statements)

References 18 publications

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“…1). In the current study, a decrease in graft size from 2 to 12 weeks was observed in all groups, which was consistent with other studies [28, 29]. The absorption period of dead adipocytes by macrophage phagocytosis within 3 months after transplantation accounts for the atrophy of the grafted fat [26].…”

Section: Discussionsupporting

confidence: 92%

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: Discussionsupporting

confidence: 92%

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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“…The wide variations in the residual graft volumes between mice injected with fat from the same donor also raised questions. Another study found inter-mouse variations for small grafts (0.3 ml) of approximately 8.44 % (Kokai et al, 2017), whereas our results attained an average of 13.8 % variation. A possible explanation for the increased variation may be that the larger size of the graft may result in variable vascularization rate in different animals, leading to uneven inner fat cell survival due to different oxygen and nutrient availability.…”

Section: Discussioncontrasting

confidence: 87%

The CD34+ Cell Number Alone Predicts Retention of the Human Fat-Graft Volume in a Nude Mouse Model

Hromádková,

Francová,

Báječný

et al. 2019

Fol. Biol.

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Prediction of the final transferred fat volume is essential for the success of fat grafting, but remains elusive. Between 20 and 80 % of the initial transplanted volume can be reabsorbed. Although graft survival has many determinants, CD34+ progenitor cells from the vascular stroma of adipose tissue play a central role by promoting growth of blood vessels and adipocytes. We aimed to verify the hypothesis that a higher proportion of total CD34+ cells in the transplant is associated with better preservation of the graft volume. Human lipoaspirates from 16 patients were processed by centrifugation and two grafts per donor were subcutaneously injected into 32 nude mice in 1 ml volumes in the right upper flank area. The volume of each graft was measured using a preclinical MRI scanner immediately after grafting and at three months. The percentage of CD34+ cells in the graft before implantation was determined by flow cytometry. The final graft volume at three months after implantation directly correlated with the percentage of CD34+ cells in the grafted material (r = 0.637, P = 0.019). The minimum retention of the fat graft was 28 % and the maximum retention was 81 %, with an average of 54 %. Our study found that fat retention after fat transfer directly correlated with the fraction of CD34+ cells in the graft. The simple and fast determination of the CD34+ cell percentage on site can help predicting outcomes of fat transplantation.

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“…To clarify the effect of hADSC-Exo on adipose graft retention, hADSC-Exo and HFF-Exo were cotransplanted with adipose grafts under the skin of nude mice in this study and observed that hADSC-Exo have a better retention rate than HFF-Exo (Figure 2). Interestingly, we observed that the weight and volume of fat grafts decreased gradually over time in both groups, which could be attributed to the progression of fat grafting, mainly involving cysts, calcification, nodules, fat necrosis, fibrosis, and survival, and eventually stabilization [26,34,35]. In addition, fat number and integrity of adipose grafts were significantly higher in the hADSC-Exo group than in the HFF-Exo group (Figures 3(a) and 3(b)).…”

Section: Discussionmentioning

confidence: 88%

Adipose-Derived Stem Cells Exosomes Improve Fat Graft Survival by Promoting Prolipogenetic Abilities through Wnt/β-Catenin Pathway

Chen

Xiong

et al. 2022

Stem Cells International

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Autologous fat grafting has been widely used in plastic surgery in recent years, but the unstable retention of fat graft has always been a key clinical problem. Adipose tissue has poor tolerant to ischemia, so the transplanted adipose tissue needs to rebuild blood supply at an early stage in order to survive stably. Our previous study has found that comparing to human foreskin fibroblast exosome (HFF-Exo), human adipose-derived stem cells exosome (hADSC-Exo) can significantly improve the proliferation of vascular endothelial cells and the angiogenic effect of artificial dermal preconstructed flaps. Therefore, the ability of hADSC-Exo to improve the retention of adipose grafts and its potential regenerative mechanism aroused our strong interest. In this study, we applied hADSC-Exo and HFF-Exo to adipose grafts and explored the potential regeneration mechanism through various means such as bioinformatics, immunofluorescence, immunohistochemistry, and adipogenic differentiation. The results showed that hADSC-Exo can significantly promote grafts angiogenesis and adipogenic differentiation of ADSC to improve the retention of fat grafts and may downregulate the Wnt/β-catenin signaling pathway to promote the adipogenic differentiation. In summary, our results provide a theoretical basis for the clinical translation of hADSC-Exo in fat grafting.

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Optimization and Standardization of the Immunodeficient Mouse Model for Assessing Fat Grafting Outcomes

Cited by 14 publications

References 18 publications

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

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

The CD34+ Cell Number Alone Predicts Retention of the Human Fat-Graft Volume in a Nude Mouse Model

Adipose-Derived Stem Cells Exosomes Improve Fat Graft Survival by Promoting Prolipogenetic Abilities through Wnt/β-Catenin Pathway

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