Wenjie Zhang’s research while affiliated with Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and other places

What is this page?


This page lists works of an author who doesn't have a ResearchGate profile or hasn't added the works to their profile yet. It is automatically generated from public (personal) data to further our legitimate goal of comprehensive and accurate scientific recordkeeping. If you are this author and want this page removed, please let us know.

Publications (112)


Enhanced osteo-angiogenic coupling by a bioactive cell-free fat extract (CEFFE) delivered through electrospun fibers
  • Article

December 2024

·

8 Reads

Journal of Materials Chemistry B

Donghong Li

·

Tingting Xu

·

Xiaoli Wang

·

[...]

·

Fat extract (FE) components released from the FE-PDA@PCL/GT fiber mesh promoted paracrine signaling communication between osteoblastic and endothelial cells. This interaction together with FE, contributed to the enhanced osteo–angiogenic coupling.


(A) Experimental workflow. (B) A diagram of the injection sites. (C) The state of CEFFE in a 1 mL syringe. (D) Representative infraorbital 2D images (Patient 7 and Patient 10). (E) Representative skin texture images (Patient 2 and Patient 7), with white arrows indicating infraorbital pigmentation as positioning markers.
(A) Changes in WSRS between baseline and the 12‐month follow‐up. (B–D) Skin wrinkle improvement assessments at the 3‐, 6‐, and 12‐month follow‐ups, including SEr%, SEsm%, and SEw%. (E–G) Skin elasticity improvement assessments at the 3‐, 6‐, and 12‐month follow‐ups, including R2%, R5%, and R7%. (H) TEWL assessments at the 3‐, 6‐, and 12‐month follow‐ups.
Autologous Cell‐Free Fat Extract: A Novel Approach for Infraorbital Rejuvenation—A Pilot Study
  • Article
  • Full-text available

December 2024

·

13 Reads

Background and Objective CEFFE (Cell‐free fat extract) treatment for periocular fine lines requires thorough clinical evaluation to determine its efficacy and safety in enhancing skin quality. The research enrolled 10 healthy female participants aged 31–58, focusing on skin texture, elasticity, and barrier function. Methods and Results CEFFE treatment demonstrated significant benefits, with notable improvements observed as early as 3 months posttreatment, which continued throughout the 12‐month follow‐up period. Objective assessments revealed reductions in SEr% and SEw%, indicative of reduced skin roughness and wrinkles, particularly pronounced after the third month of treatment. Enhanced skin elasticity, as indicated by improvements in R2%, R5%, and R7%, was observed, with the most significant enhancements noted at the 6‐month follow‐up. Furthermore, TEWL decreased consistently, highlighting CEFFE's potential in maintaining the skin's barrier function and moisture retention. High patient satisfaction levels, with 70% expressing satisfaction ranging from satisfied to very satisfied, underscored CEFFE's clinical significance. Conclusions CEFFE demonstrates potential as an effective and safe intervention for addressing periocular fine lines, providing a solution for fine lines while ensuring skin health (ChiCTR1900024329).

Download

Cell-Free Fat Extract with Anti-melanogenic Property Improves the Appearance of Infraorbital Dark Circles: A Preliminary Clinical Study

November 2024

·

2 Reads

Aesthetic Plastic Surgery

The formation of infraorbital dark circles involves various factors including hyperpigmentation, skin aging and laxity. This study is to investigate whether cell-free fat extract (CEFFE) inhibits melanin synthesis and improves the appearance of infraorbital dark circles. Imaging systems analysed the melanin content in three groups of zebrafish embryos treated with 0 (CTRL), 100, and 200μg/mL of CEFFE. Eleven patients with infraorbital dark circles were enrolled and received intradermal injections of autologous CEFFE. Clinical trial assessments included subjective assessments (Global Aesthetic Improvement Scale and Likert satisfaction scale) and objective assessments (standard two-dimensional photographs, VISIA® photographs, and infraorbital skin colour measurement). In the experiment of zebrafish embryos, the melanin content of CEFFE treatment was significantly reduced. In clinical trial, 72.73% of patients considered CEFFE treatment for infraorbital dark circles to be effective, and more than half of the patients were satisfied with the treatment. In the evaluation of skin colour at the inner, middle, and outer edges of the infraorbital dark circles, there was a gradual improvement in infraorbital skin colour after each treatment and at the 3-month follow-up, with a statistically significant improvement in skin colour on the outer edge of the infraorbital dark circles (p < 0.05). Simultaneously, we observed a reduction in periocular wrinkles, with a significant difference at the 3-month follow-up (p < 0.05). The events observed included bruising, erythema, and oedema, which resolved spontaneously. Our study demonstrated that CEFFE inhibits melanogenesis and is a safe and effective treatment for infraorbital dark circles. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.



Annexin-A5 monomer as a membrane repair agent for the treatment of renal ischemia-reperfusion injury

May 2024

·

18 Reads

·

1 Citation

Molecular Biology Reports

Background Renal ischemia-reperfusion injury (IRI) is one of the causes of acute kidney injury. Annexin A5 (AnxA5), a calcium-dependent cell membrane-binding protein, shows protective effects in various organ IRI models. This study explored the therapeutic effect of exogenous AnxA5 monomer protein on renal IRI and its potential mechanism of action. Methods and results Different doses of AnxA5 were injected intravenously to treat bilateral renal IRI in SD rats. This model confirmed the protective effects of AnxA5 on kidney structure and function. In vitro, HK-2 cells were subjected to hypoxia for 12 h, followed by restoration of normal oxygen supply to simulate IRI. In vitro experiments demonstrated the mechanism of action of AnxA5 by measuring cellular activity and permeability. A comparison of the mutant AnxA5 protein M23 and the application of a calcium-free culture medium further validated the protective effect of AnxA5 by forming a network structure. Conclusions Exogenous AnxA5 monomers prevented renal IRI by binding to the damaged renal tubular epithelial cell membrane, forming a two-dimensional network structure to maintain cell membrane integrity, and ultimately prevent cell death.


Annexin A5 Derived from Cell-free Fat Extract Attenuates Osteoarthritis via Macrophage Regulation

May 2024

·

16 Reads

·

2 Citations

International Journal of Biological Sciences

Osteoarthritis (OA) is a challenging degenerative joint disease to manage. Previous research has indicated that cell-free fat extract (CEFFE) may hold potential for OA treatment. This study investigated the role of Annexin A5 (AnxA5) within CEFFE in regulating macrophage polarization and protecting chondrocytes. In vitro experiments demonstrated that AnxA5 effectively inhibited M1 macrophage polarization by facilitating toll-like receptor (TLR) 4 internalization and lysosomal degradation through calcium-dependent endocytosis. This process decreased TLR4 expression, suppressed pro-inflammatory mediator release, and reduced the production of reactive oxygen species. Furthermore, AnxA5 displayed protective effects against chondrocyte necrosis and apoptosis. In vivo, studies revealed that intra-articular administration of AnxA5 ameliorated pain symptoms in a monosodium iodoacetate-induced osteoarthritis rat model. Histological analyses indicated a decrease in synovial inflammation and mitigation of cartilage damage following AnxA5 treatment. These results underscored the potential of AnxA5 as a therapeutic option for OA due to its capacity to regulate macrophage polarization and maintain chondrocyte viability. Further investigation into the specific mechanisms and clinical applications of AnxA5 may help improve the management of OA.


Fig. 1. A5 Accelerates Diabetic Wound Healing. A: Schematic representation of the animal experiment. B: Representative macroscopic photographs of wounds from the CTRL group, GelMA group, and GelMA-A5 group at days 0, 3, 7, 10, and 14. C: Percentage of wound area at days 0, 3, 7, 10, and 14. Data are presented as mean ± SEM, with n ¼ 6 for each group. Statistical analyses were performed by comparing the GelMA and GelMA-A5 groups to the CTRL group, where *p < 0.05, **p < 0.05; and by comparing the GelMA and GelMA-A5 groups, where #p < 0.05, ##p < 0.05.
Fig. 2. Histological Changes in Diabetic Wounds Following Treatment of A5 On the 14th Day. A: HE staining of the CTRL group, GelMA group, and GelMA-A5 group. B: Masson's trichrome staining of the CTRL group, GelMA group, and GelMA-A5 group. The scale bar for the full wound tissue display is 1000 mm, and the scale bar for the local wound tissue display is 250 mm.
Fig. 3. The effect of A5 on regulating inflammation in diabetic wounds. A. Representative images of immunohistochemical anti-CD68 staining in diabetic wounds was performed. B. Quantitative analysis of integral optical density of anti-CD68-positive cell. C. Representative images of immunofluorescence anti-CD86 and anti-CD206 staining was performed. D&E. Quantitative analysis of fluorescence intensity of anti-CD86 and anti-CD206. F. Relative expression levels of IL-1b, IL-6, TGF-b and CD206 detected by qRT-PCR in diabetic wounds from the CTRL group, GelMA group, and GelMA-A5 group. Data are presented as mean ± SEM. Statistical analyses were performed by comparing the GelMA and GelMA-A5 groups to the CTRL group, where *p < 0.05, **p < 0.05; and by comparing the GelMA and GelMA-A5 groups, where #p < 0.05, ##p < 0.05.
Fig. 4. The effect of A5 of angiogenesis and epithelial proliferation in diabetic wounds. A. Representative images of immunohistochemical anti-CD31 staining in diabetic wounds was performed. B. Quantitative analysis of capillary density of the number of anti-CD31-positive vessels. C. Representative images of immunohistochemical anti-PCNA staining in diabetic wounds was performed. D. Quantitative analysis of integral optical density of epithelial anti-PCNA-positive cell. Data are presented as mean ± SEM.
Fig. 5. A5 regulated LPS-stimulated inflammation of BMDMs. A. Morphology of LPS-stimulated primary macrophage BMDMs after 24 h of A5 treatment. B. Relative expression levels of IL-1b, IL-6, TNF-a and ARG-1 detected by qRT-PCR in LPS-stimulated BMDMs treated with A5 for 24 h. C&D. Percentages of CD86 þ cells of BMDMs after stimulated by LPS and treated with A5 detected by flow cytometry. E. Representative images of immunocytofluorescence anti-CD86 staining in LPS-stimulated BMDMs treated with A5. Data are presented
Recombinant human annexin A5 accelerates diabetic wounds healing by regulating skin inflammation

April 2024

·

20 Reads

·

1 Citation

Regenerative Therapy

Background One of the key obstacles to the healing of diabetic wound is the persistence of active inflammation. We previously demonstrated the potential of cell-free fat extract (CEFFE) to promote the healing of diabetic wounds, and annexin A5 (A5) is a crucial anti-inflammatory protein within CEFFE. This study aimed to evaluate the therapeutic potential of A5 in diabetic wounds. Methods A5 was loaded into GelMA hydrogels and applied to skin wounds of diabetic mice in vivo. The diabetic wounds with the treatment of GelMA-A5 were observed for 14 days and evaluated by histological analysis. Accessment of inflammation regulation were conducted through anti-CD68 staining, anti-CD86 and anti-CD206 staining, and qRT-PCR of wound tissue. In presence of A5, macrophages stimulated by lipopolysaccharide (LPS) in vitro, and detected through qRT-PCR, flow cytometry, and immunocytofluorescence staining. Besides, epithelial cells were co-cultured with A5 for epithelialization regulation by CCK-8 assay and cell migration assay. Results A5 could promote diabetic wound healing and regulate inflammations by promoting the transition of macrophages from M1 to M2 phenotype. In vitro experiments demonstrated that A5 exerted a significant effect on reducing pro-inflammatory factors and inhibiting the polarization of macrophages from M0 toward M1 phenotype. A5 significantly promoted the migration of epithelial cells. Conclusion Annexin A5 has a significant impact on the regulation of macrophage inflammation and promotion of epithelialization.


FIGURE 1 CEFFE promotes axon regeneration. (A) Confocal images of optic nerve longitudinal sections showing regenerating fibers labelled with CTB-555. * Represents crush site. Scale bar, 100 μm. (B) Quantification of regenerating axons at different distances distal to the lesion site. ***p < 0.001, ****p < 0.0001. Data are presented as means ± standard error of mean, n = 6 mice per group. Two-way analysis of variance with Tukey's test.
FIGURE 4
FIGURE 5 CEFFE attenuates microglia activation and modulate inflammation factors in retina. (A) Representative confocal pictures of sections showing CD11b-positive microglia (green) in retina. (GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer plexiform layer). Scale bar, 50 μm. (B) Quantification of CD11b-positive cells in GCL and entire retina. (C) Quantification of ARG, IL-10, CD206, and TGF-β mRNA expression by RT-qPCR. (D) Quantification of IL-1β, IL-6, iNOS, and TNF-α mRNA expression by RT-qPCR. One-way ANOVA and Tukey's multiple comparisons test. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 (n = 5 mice per group).
Mean inflammation factors concentration in CEFFE (n = 6, pg./ml).
Cell-free fat extract promotes axon regeneration and retinal ganglion cells survival in traumatic optic neuropathy

March 2024

·

32 Reads

·

1 Citation

Frontiers in Cellular Neuroscience

Injuries to axons within the central nervous system (CNS) pose a substantial clinical challenge due to their limited regenerative capacity. This study investigates the therapeutic potential of Cell-free fat extract (CEFFE) in CNS injury. CEFFE was injected intravitreally after the optic nerve was crushed. Two weeks post-injury, quantification of regenerated axons and survival rates of retinal ganglion cells (RGCs) were performed. Subsequently, comprehensive gene ontology (GO) an-notation elucidated the cellular origins and functional attributes of CEFFE components. Molecular mechanisms underlying CEFFE’s therapeutic effects were explored through Western blotting (WB). Additionally, levels of inflammatory factors within CEFFE were determined using enzyme-linked immunosorbent assay (ELISA), and histological staining of microglia was conducted to assess its impact on neuroinflammation. CEFFE demonstrated a significant capacity to promote axon re-generation and enhance RGCs survival. GO annotation revealed the involvement of 146 proteins within CEFFE in axonogenesis and neurogenesis. WB analysis unveiled the multifaceted pathways through which CEFFE exerts its therapeutic effects. Elevated levels of inflammatory factors were detected through ELISA, and CEFFE exhibited a modulatory effect on microglial activation in the retinal tissue following optic nerve crush (ONC). The present study highlights the therapeutic promise of CEFFE in the management of CNS injuries, exemplified by its ability to foster axon regeneration and improve RGCs survival.



Figure 2
Figure 3
Figure 7
Annexin-A5 monomer as a membrane repair agent for the treatment of renal ischemia-reperfusion injury

February 2024

·

16 Reads

Background: Renal ischemia-reperfusion injury (IRI) is one of the causes of acute kidney injury. Annexin A5 (AnxA5) as a calcium-dependent cell membrane binding protein has shown good protective effects in various organ IRI models. This study explored the therapeutic effect of exogenous AnxA5 monomer protein on renal IRI and its potential mechanism. Methods: In vivo, different doses of AnxA5 were injected intravenously to treat bilateral renal IRI models in SD rats. This model confirms the protective effect of AnxA5 on the structure and function of the kidneys. In vitro, HK-2, the renal tubular epithelial cells, was subjected to hypoxia for 12 hours, followed by restoration of normal oxygen supply to simulate IRI. In vitro experiments have demonstrated the mechanism of action of AnxA5 by measuring cell activity and permeability. The comparison of the mutant AnxA5 protein M23 and the application of calcium-free culture medium further validated the protective effect of AnxA5 by forming a network structure. Results: In vivo, AnxA5 monomer improved kidney function damage caused by IRI and prevented the deterioration of the pathological structure. In vitro, AnxA5 protected cell viability, reduced cell membrane permeability, and inhibited cell apoptosis induced by IRI treatment. However, AnxA5 lost its protective effect in the calcium-free culture medium and the M23 that lack the ability of forming a two-dimensional network structure could not reduce cell membrane permeability and lost its protective effect on cell viability, indicating that the formation of a two-dimensional network structure of AnxA5 is critical to the repair of the cell membrane. Conclusions: Exogenous AnxA5 monomer could prevent renal IRI by binding to the damaged renal tubular epithelial cell membrane, forming a two-dimensional network structure to maintain cell membrane integrity, and ultimately prevent cell death.


Citations (73)


... There is an extensive body of literature demonstrating the multiple properties of endogenous and recombinant Annexin A5 in vitro and in vivo. The pharmacologic effects of recombinant human Annexin A5 that might be of relevance to RVO and other retinal diseases include its anti-adherent [11], anti-inflammatory [18,24], anti-thrombotic [20], and cell-protecting effects [15,109]. ...

Reference:

New Therapeutic Strategies in Retinal Vascular Diseases: A Lipid Target, Phosphatidylserine, and Annexin A5—A Future Theranostic Pairing in Ophthalmology
Annexin-A5 monomer as a membrane repair agent for the treatment of renal ischemia-reperfusion injury

Molecular Biology Reports

... The improving understanding of PS's biology, such as the predominant PS target availability on the cell surface under pathologic circumstances, makes it an attractive target for diagnostic [34] and therapeutic interventions. Indeed, PS has been postulated to be a pharmacologic target in a number of non-ophthalmic diseases, and the therapeutic use of Annexin A5 to target PS has been proposed in RVO [11], cancer [17], sepsis [18,24], viral infections including COVID-19 [25,26], inflammatory bowel disease [27], osteoporosis [28], Alzheimer's [13], vaso-occlusive crisis in sickle cell disease [29], diabetic skin wounds [16], and cardiovascular disease [14]. Multiple independent pre-clinical proof of concept efficacy studies related to using recombinant human Annexin A5 to target PS in vivo are available, although this is not within the scope of this review. ...

Recombinant human annexin A5 accelerates diabetic wounds healing by regulating skin inflammation

Regenerative Therapy

... Previous studies show that CEFFE activates the TGFβ pathway and might promote cell proliferation and antagonise apoptosis of ovary granulosa cells. CEFFE promotes the proliferation of human dermal papilla cells by inhibiting cell cycle arrest and apoptosis [12,29]. Compared with the control group, the CEFFE medium significantly improved blastocyst cell numbers and hatched blastocyst development and reduced apoptosis frequency in aged mice. ...

Cell-free fat extract restores hair loss: a novel therapeutic strategy for androgenetic alopecia

Stem Cell Research & Therapy

... Moreover, CEFFE is a liquid without cellular components, thus preventing the safety issues associated with cell-based therapies. In addition, safety evaluations suggested that CEFFE had no adverse effects on the offspring's growth and biosafety in mice and rats [12][13][14]. Therefore, we hypothesised that CEFFE supplementation in culture media might be particularly beneficial for the in vitro culture of embryos. ...

Cell-free fat extract-loaded microneedles attenuate inflammation-induced apoptosis and mitochondrial damage in tendinopathy
  • Citing Article
  • August 2023

Materials Today Bio

... Cell-free fat extract (CEFFE) is a novel experimental treatment method that is currently being researched primarily in China for applications such as osteoarthritis attenuation [96], tissue regeneration [97] and osteoclastogenic modulation [98]. It is rich in growth factors and anti-inflammatory properties, both of which have had positive effects in other studies mentioned in this review. ...

Fat Extract Modulates Calcium Signaling and Protects against Hyperactive Osteoclastogenesis in Bone Remodeling with Antioxidant Capacity

... The main shortcoming of this study is that we only explored the effects of DPSCs-Exos on some biological behaviors of KFs and NFs in vitro, but did not carry out in vivo research and further explore its mechanism. Although the advantages of using animal models for in vivo experiments are obvious, the pathological manifestations of keloids are only seen in human subjects 53,54 and, due to the vast physiological and immunological differences between humans and animals 55,56 , this calls into question the reliability of animal models in clinical studies simulating human keloids [57][58][59] . In addition, the exact mechanism of keloid formation is still unclear, and its pathological process involves a complex immune response. ...

Combined analyses of RNA-sequence and Hi-C along with GWAS loci—A novel approach to dissect keloid disorder genetic mechanism

... Sphingomyelin liposomes encapsulating the photosensitizer IR780 are used to stabilize an oxygen-carrying perfluorocarbon (PFC) nanoemulsion, forming the liposomal NB. FE, a cell-free liquid extracted from human fat tissues, has demonstrated regenerative potential in applications such as ischemic stroke [13], fat graft survival [14], and hindlimb ischemia [15] due to its hydrophilic nature, low immunogenicity, and enrichment in growth factors. We hypothesized that FE could be integrated into a thermosensitive and injectable F-127 hydrogel for wound healing purposes. ...

Targeted delivery of fat extract by platelet membrane-cloaked nanocarriers for the treatment of ischemic stroke

... In addition to mimicking the nonlinear stress-strain behavior of ligaments, PLLA fibers are instructive in cell morphology and promote ligament phenotypic gene expression. Zhenying Chen et al. [6] prepared crimped poly l-lactic acid/poly (3-hydroxybut yrate-co-3-hydroxyvalerate) (PLLA/PHBV) fibers to mimic tendon tissue, and these fibers were observed to be more effective in enhancing collagen production and assembly under mechanical stimulation. ...

Synergistic effects of mechanical stimulation and crimped topography to stimulate natural collagen development for tendon engineering

Acta Biomaterialia

... 9 The CEFFE is abundant in growth factors and other bioactive molecules, potentially promoting tissue healing and regeneration. [9][10][11][12][13][14][15] In recent years, CEFFE has been widely applied in medical aesthetics, plastic surgery, tissue engineering, etc., contributing to wound healing, reducing signs of skin aging, and enhancing tissue volume. [16][17][18][19][20] Therefore, we believe that further processing the residual fat from HQF preparation into CEFFE may significantly enhance the survival rate of transplanted fat. ...

Cell-free fat extract attenuates osteoarthritis via chondrocytes regeneration and macrophages immunomodulation

Stem Cell Research & Therapy