Fat Extract Improves Random Pattern Skin Flap Survival in a Rat Model

Cai, Yu; Yu, Ziyou; Yu, Qian; Zheng, Hongjie; Xu, Yuda; Deng, Mingwu; Wang, Xiangsheng; Zhang, Lu; Zhang, Wenjie; Li, Wei

doi:10.1093/asj/sjz112

Cited by 33 publications

(25 citation statements)

References 39 publications

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“…The concentration of the CEFFE was approximately 5 ug/ul, which contained 2 pg/ul of BDNF. As we have shown, CEFFE contains diverse neurotrophic factors [8,15] and may promote axon regeneration that is more robust than that promoted by the use of a single neurotrophic factor; this nding is consistent with those of previous studies.…”

Section: Discussionsupporting

confidence: 92%

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Cell-free Fat Extract Promote Axon Regeneration: a Pre-clinical Study.

Sun¹,

Wang

Chen³

et al. 2021

Preprint

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Background: Injured axons of the central nervous system (CNS) hardly regenerate due to their poor intrinsic regeneration ability and adverse microenvironment at the site of injury; previous studies aimed to investigate both the above-mentioned factors and achieved some success. Compared with the gene-editing technology, stem cell therapy has unique advantages, such as low risk of tumor formation and ease-of-use, among others. However, traditional stem cell therapy is hindered by safety and immunogenicity issues. Previously, we developed a cell-free extract directly from human fat tissue (CEFFE) and demonstrated its proangiogenic capacity. Herein, we aimed to evaluate its potential therapeutic effect in injured CNS.Methods: Therapeutic potential of CEFFE in injured CNS was investigated, using a mouse optic nerve crush model. After the optic nerve was crushed, CEFFE was injected intravitreally. Two weeks post-injury, the number of regenerated axons was measured at different distances from the crush site (250, 500, 750, 1000, and 1500 µm). In addition, surviving retinal ganglion cells (RGCs) were counted. Cellular locations and catalogs of CEFFE were analyzed by gene ontology (GO) annotation. Western blotting (WB) was performed to evaluate the therapeutic effects of CEFFE on the molecular level. An enzyme-linked immunosorbent assay (ELISA) was used to examine the levels of inflammatory factors in CEFFE. Results: Compared with brain-derived neurotrophic factor (BDNF), CEFFE effectively promoted axon regeneration and RGCs survival. GO annotation showed that 146 proteins were involved in axon genesis or neurogenesis, most of which were located intracellularly. WB and ELISA results showed that CEFFE acted on diverse pathways and involved high levels of inflammatory factors. Conclusions: The present findings have shown that CEFFE may promote axon regeneration and increase RGCs survival. The levels of factors involved in CEFFE were much higher than those observed in the traditional secretome; CEFFE involves multiple factors and affects several mechanisms. This study has revealeded the potential application of CEFFE for the treatment of CNS injury.

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Section: Discussionsupporting

confidence: 92%

“…Given our previous ndings on CEFFE's positive effects on wound healing, [8][9][10][11]15] we examined its effects on injured CNS repair. In the present study, we demonstrated that CEFFE has neuroprotective and axon regenerating effects on injured RGCs, which suggest its potential clinical applications.…”

Section: Discussionmentioning

confidence: 99%

Cell-free Fat Extract Promote Axon Regeneration: a Pre-clinical Study.

Sun¹,

Wang

Chen³

et al. 2021

Preprint

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“…with 250 μl of PBS as vehicle (TS + vehicle), and a tail-suspended group that was injected i.p. with 250 μl [the administration dose of CEFFE was referred to our previous published article (Cai et al, 2019)] of CEFFE (TS + CEFFE) twice a week for 4 weeks after suspension for 3 weeks, and the mice were still in tail suspension during the administration period. The extraction of CEFFE was performed as described previously (Yu et al, 2018).…”

Section: Ceffe Preparationmentioning

confidence: 99%

“…Furthermore, CEFFE is a cell-free liquid that greatly reduces its immunogenicity and ensures its safety during treatment. Our previous studies have found it to have proangiogenic activity (Yu et al, 2018) and found that it improved skin flap survival (Cai et al, 2019), improved fat graft survival (Zheng et al, 2019), and promoted the healing of diabetic wounds (Wang et al, 2020;Yin et al, 2020). CEFFE contains cytokines and growth factors such as IGF1, bFGF, and other growth factors, which can promote bone growth (Pedersen and Febbraio, 2012).…”

Section: Introductionmentioning

confidence: 99%

Cell-Free Fat Extract Prevents Tail Suspension–Induced Bone Loss by Inhibiting Osteocyte Apoptosis

Cui

et al. 2022

Front. Bioeng. Biotechnol.

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Introduction: As the space field has developed and our population ages, people engaged in space travel and those on prolonged bed rest are at increasing risk for bone loss and fractures. Disuse osteoporosis occurs frequently in these instances, for which the currently available anti-osteoporosis agents are far from satisfactory and have undesirable side effects. CEFFE is a cell-free fraction isolated from nanofat that is enriched with a variety of growth factors, and we aim to investigate its potential therapeutic effects on disuse osteoporosis.Methods: A tail suspension–induced osteoporosis model was applied in this study. Three weeks after tail suspension, CEFFE was intraperitoneally injected, and PBS was used as a control. The trabecular and cortical bone microstructures of the tibia in each group were assessed by μCT after 4 weeks of administration. Osteocyte lacunar-canalicularity was observed by HE and silver staining. In vitro, MLO-Y4 cell apoptosis was induced by reactive oxygen species (ROSUP). TUNEL staining and flow cytometry were used to detect apoptosis. CCK-8 was used to detect cell proliferation, and Western blotting was used to detect MAPK signaling pathway changes.Results: CEFFE increased the bone volume (BV/TV) and trabecular number (Tb.N) of the trabecular bone and increased the thickness of the cortical bone. HE and silver staining results showed that CEFFE reduced the number of empty lacunae and improved the lacuna-canalicular structure. CEFFE promoted osteocyte proliferative capacity in a dose-dependent manner. CEFFE protected MLO-Y4 from apoptosis by activating the serine/threonine-selective protein kinase (ERK) signaling pathways.Conclusion: CEFFE attenuated immobilization-induced bone loss by decreasing osteocyte apoptosis. CEFFE increased the survival of osteocytes and inhibited osteocyte apoptosis by activating the ERK signaling pathway in vitro.

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“…Lu et al have observed the effect of ATE on adipose tissue regeneration in an engineering chamber model, in which regenerated adipose tissue of ATE group exhibited more considerable volume, better morphology and structure, a thinner capsule, and more vessels compared with control group [ 39 ]. Cai et al revealed that ATE (named as fat extract in their research) isolated from human fat contained proangiogenic growth factors that promoted proliferation, migration, and tube formation in HUVEC in vitro, while the treatment of ATE increased capillary density of skin flap, thereby reducing flap necrosis in a rat model [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Comparison of two cell-free therapeutics derived from adipose tissue: small extracellular vesicles versus conditioned medium

Dai

Zhou

et al. 2022

Stem Cell Res Ther

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Background Cell-free therapy has been inspired as a promising approach to overcome the limitations of traditional stem cell therapy. However, the therapeutic effect between extracellular vesicles and conditioned medium with the same source had not been compared. Our previous studies have shown that both the conditioned medium of adipose tissue (adipose tissue extract, ATE) and its further purification product small extracellular vesicles (sEV-AT) contributed to adipose tissue regeneration. In this study, we aimed to compare the ATE and sEV-AT in composition, inductivity on cells and de novo adipose regenerative potential. Methods The characteristics of sEV-AT and ATE were compared through protein and particle yield, particle size distribution and composition. The inductivity of sEV-AT and ATE on cells were compared through co-culture of sEV-AT or ATE with ASC, HUVEC and RAW264.7 in vitro. The capacity of promoting de novo adipogenesis was compared by implanting the silicone tube containing sEV-AT or ATE subcutaneously in vivo. Results More particles and concentrated particle size distribution were detected in sEV-AT. In turn, more soluble factors and multiple peaks in particle size distribution were detected in ATE. In 1662 common proteins of sEV-AT and ATE, there were 984 (59.2%) proteins enriched twice more in sEV-AT than in ATE. With the prerequisite of equivalent protein concentration, sEV-AT outperformed ATE in promoting proliferation, migration and regeneration potential of cells those contributing adipose tissue regeneration in vitro. Furthermore, sEV-AT expedited the de novo adipose tissue regeneration and angiogenesis at the early stage than ATE in vivo, but sEV-AT and ATE group formed similar neoadipose tissue and new vessels at week 12. Conclusions Our results provided a direct comparison between EV and conditioned medium as cell-free therapeutic strategy. Both sEV and ATE had specific biological signature to facilitate tissue repair. Considering the convenience of extraction and acceptable effect, ATE represented a feasible product of cell-free therapy, providing another option for different situations in clinical application. Furthermore, the complex contents of both sEV-AT and ATE should be studied comprehensively to avoid possible negative effects and to ensure sufficient safety for clinical applications.

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Fat Extract Improves Random Pattern Skin Flap Survival in a Rat Model

Cited by 33 publications

References 39 publications

Cell-free Fat Extract Promote Axon Regeneration: a Pre-clinical Study.

Cell-free Fat Extract Promote Axon Regeneration: a Pre-clinical Study.

Cell-Free Fat Extract Prevents Tail Suspension–Induced Bone Loss by Inhibiting Osteocyte Apoptosis

Comparison of two cell-free therapeutics derived from adipose tissue: small extracellular vesicles versus conditioned medium

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