Activated macrophages as key mediators of capsule formation on adipose constructs in tissue engineering chamber models

Zhan, Weiqing; Lu, Feng

doi:10.1002/cbin.10731

Cited by 7 publications

(5 citation statements)

References 49 publications

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“…Notably, our findings showed that IL‐2 levels increased and peaked at 24 hr. Moreover, some studies have shown that macrophages secrete various proinflammation factors, such as IL‐6 and IL‐2 (Brown, Ratner, Goodman, Amar, & Badylak, ; Debels et al, ; Zhan & Lu, ). However, the number of macrophages peaked at 2 weeks, which was later than the peak time of IL‐2.…”

Section: Discussionmentioning

confidence: 99%

CD8+ T cells are involved in early inflammation before macrophages in a rat adipose tissue engineering chamber model

Yuan

Liao

et al. 2019

J Tissue Eng Regen Med

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Adipose tissues regenerated using tissue engineering chambers (TECs) show the potential for applications in reconstruction of soft tissue defects. Previous studies have shown that early inflammation plays a key role in angiogenesis and adipogenesis required for adipose tissue generation. However, the sequence of events of the early inflammatory cascade is unclear. In this study, we investigated the role of early inflammatory cells in adipose tissue engineering using a rat TEC model. Rats in the TEC model were divided into five groups: the control group, the zymosan A‐treated group, the 5‐AIQ‐treated group, the imatinib‐treated group, and the CD8+ T cell injection group. Fat pad volume, angiogenesis, adipogenesis, inflammatory factor levels, and inflammatory cell infiltration in chambers after implantation were evaluated at different time points. The volume of fat pads of was higher in the zymosan A‐treated and CD8+ T cell injection groups than other groups, and these two groups also showed higher levels of proinflammatory factors, greater numbers of CD31+ cells and perillipin+/Ki67+ cells, and higher macrophage infiltration. The infiltration of CD8+ T cell peaked at 3 days after implantation, which was earlier than that of macrophages. However, inhibition of CD8+ T cells reduced the recruitment of macrophages and lowered inflammation in the TECs. CD8+ T cells played a key role in promoting inflammation at earlier stages than macrophages in adipose TECs. Increased levels of interleukin‐2 secretion by CD8+ T cells resulted in recruitment of more infiltrating macrophages to enhance inflammation, as required for adipose tissue regeneration.

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Section: Discussionmentioning

confidence: 99%

CD8+ T cells are involved in early inflammation before macrophages in a rat adipose tissue engineering chamber model

Yuan

Liao

et al. 2019

J Tissue Eng Regen Med

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“…9 Moreover, reviewing the literature, it has been found that these protein factors, such as VEGF and EGF, can promote neovascularization, while BDNF, HGF, PDGF, GDNF, and others can inhibit M1 polarization and promote the M2 polarization of macrophages. 23,[48][49][50][51][52][53][54][55][56] Additionally, M2 macrophages can promote angiogenesis in vivo. 57 In this study, we validated these factors using ELISA (Table 1) and believe that they be important reasons for promoting macrophage M2 polarization.…”

Section: Discussionmentioning

confidence: 99%

“…detected many important protein factors in CEFFE, including BDNF, GDNF, TGF‐β, HGF, bFGF, VEGF, PDGF, EGF, NT‐3, and G‐CSF 9 . Moreover, reviewing the literature, it has been found that these protein factors, such as VEGF and EGF, can promote neovascularization, while BDNF, HGF, PDGF, GDNF, and others can inhibit M1 polarization and promote the M2 polarization of macrophages 23,48–56 . Additionally, M2 macrophages can promote angiogenesis in vivo 57 .…”

Section: Discussionmentioning

confidence: 99%

“…The inflammatory microenvironment is a significant factor leading to fat absorption, and macrophage polarization plays a critical role in the inflammatory microenvironment. 23,51,52 In vivo results showed that the CEFFE group had more M2 macrophages and fewer M1 macrophages, indicating that CEFFE can regulate the inflammatory microenvironment towards an anti-inflammatory state (Figure 3). To further validate this viewpoint, we conducted in vitro experiments that clearly showed CEFFE can promote macrophage polarization towards the M2 phenotype (Figure 10).…”

Section: Discussionmentioning

confidence: 99%

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Enhancing high‐quality fat survival: A novel strategy using cell‐free fat extract

Nie,

Tian,

Xiao

et al. 2024

The FASEB Journal

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High‐quality fat (HQF) improves the survival rate of fat and volumetric filling compared to traditional Coleman fat. However, this HQF strategy inevitably leads to a significant amount of unused fat being wasted. “CEFFE” (cell‐free fat extract) is an acellular aqueous‐phase liquid, rich in bioactive proteins. The remaining fat from preparing HQF can be further processed into CEFFE to promote the survival of HQF. HQF was obtained and the remaining fat was processed into CEFFE, then HQF was transplanted subcutaneously in nude mice. Animal studies showed that CEFFE significantly improved the survival rate of HQF. Histological analysis revealed that CEFFE improved the survival rate of HQF, by enhancing cell proliferation activity, reducing apoptosis, increasing angiogenesis, and improving the inflammatory state. Under simulated anaerobic conditions, CEFFE also improved the viability of HQF. In vitro, studies demonstrated that CEFFE enhanced the survival rate of HQF through multiple mechanisms. Transcriptomic analysis and qPCR showed that CEFFE increased the expression of angiogenesis‐related genes in ADSCs while enhancing their proliferation‐related gene expression and suppressing the expression of three differentiation‐related genes. Moreover, functional experiments demonstrated that CEFFE‐induced ADSCs exhibited stronger proliferation and adipogenic differentiation abilities. Tube formation and migration assays revealed that CEFFE promoted tube formation and migration of HUVECs, indicating its inherent pro‐angiogenic properties. CEFFE facilitated the development of M0 to M2 macrophages, suggesting its role in improving the inflammatory state. This innovative clinical strategy optimizes HQF transplantation strategy, minimizing fat wastage and enhancing the efficiency of fat utilization.

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“…Moreover, Crdf induced transient M2-polarized macrophages infiltration, in contrast to the chronic M1 macrophages in the Df group. Previous studies had shown that rapid inflammatory responses could activate chemotaxis of host-derived mesenchymal stem cells and promote angiogenesis in the early stage of grafting ( Zhan and Lu, 2017 ; Cai et al, 2018 ). While persistent high levels of macrophage infiltration inhibit adipogenesis and cause severe fibrosis ( Cai et al, 2017a , b ).…”

Section: Discussionmentioning

confidence: 99%

Characterized the Adipogenic Capacity of Adipose-Derived Stem Cell, Extracellular Matrix, and Microenvironment With Fat Components Grafting

Jiang

Cai

Guan

et al. 2021

Front. Cell Dev. Biol.

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Background: Autologous fat grafting has been a widely used technique; however, the role of adipose-derived stem cells (ASCs), extracellular matrix (ECM), and microenvironment in fat regeneration are not fully understood.Methods: Lipoaspirates were obtained and processed by inter-syringe shifting to remove adipocytes, yielding an adipocyte-free fat (Aff). Aff was then exposed to lethal dose of radiation to obtain decellularized fat (Df). To further remove microenvironment, Df was rinsed with phosphate-buffered saline (PBS) yielding rinsed decellularized fat (Rdf). Green fluorescent protein (GFP) lentivirus (LV-GFP)-transfected ASCs were added to Df to generate cell-recombinant decellularized fat (Crdf). Grafts were transplanted subcutaneously into nude mice and harvested over 3 months.Results: Removal of adipocytes (Aff) didn’t compromise the retention of fat grafts, while additional removal of stromal vascular fraction (SVF) cells (Df) and microenvironment (Rdf) resulted in poor retention by day 90 (Aff, 82 ± 7.1% vs. Df, 28 ± 6.3%; p < 0.05; vs. Rdf, 5 ± 1.2%; p < 0.05). Addition of ASCs to Df (Crdf) partially restored its regenerative potential. Aff and Crdf exhibited rapid angiogenesis and M2-polarized macrophages infiltration, in contrast to impaired angiogenesis and M1-polarized inflammatory pattern in Df. GFP + ASCs participated in angiogenesis and displayed a phenotype of endothelial cells in Crdf.Conclusion: Adipose ECM and microenvironment have the capacity to stimulate early adipogenesis while ECM alone cannot induce adipogenesis in vivo. By directly differentiating into endothelial cells and regulating macrophage polarization, ASCs coordinate early adipogenesis with angiogenesis and tissue remodeling, leading to better long-term retention and greater tissue integrity.

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Activated macrophages as key mediators of capsule formation on adipose constructs in tissue engineering chamber models

Cited by 7 publications

References 49 publications

CD8+ T cells are involved in early inflammation before macrophages in a rat adipose tissue engineering chamber model

CD8+ T cells are involved in early inflammation before macrophages in a rat adipose tissue engineering chamber model

Enhancing high‐quality fat survival: A novel strategy using cell‐free fat extract

Characterized the Adipogenic Capacity of Adipose-Derived Stem Cell, Extracellular Matrix, and Microenvironment With Fat Components Grafting

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