Efficient wound repair with skin appendage regeneration following severe trauma poses a challenge due to the scarcity of skin grafts and decreased drug effectiveness in protease‐rich wound microenvironments. Here, a multifunctional artificial skin (NIR‐mFAS) with photothermal‐triggered drug delivery capabilities is designed to actively and comprehensively improve the regenerative potential of full‐thickness wounds. The antibacterial chitosan/silk fibroin hydrogel matrix of artificial skin, cross‐linked by electrostatic interactions, effectively encapsulates and sustains the release of epidermal growth factor (EGF) to accelerate re‐epithelialization and neovascularization by promoting the migration and proliferation of repair cells. Subsequently, the photothermal responsive polydopamine nanoparticles (PDA‐NPs) dispersed in the matrix enable precise control over the release of BMP4 under the irradiation of 1064 nm NIR, thereby inhibiting scarring by reducing myofibroblasts during the proliferative stage. Importantly, the concurrent controlled release of CHIR99021 can modulate cell fate by inducing the conversion of myofibroblasts into dermal papilla‐like cells, leading to hair follicle and sebaceous gland regeneration. The NIR‐mFAS functions as an advanced delivery system for achieving high‐quality wound healing with appendage regeneration and offers a smart therapeutic approach that can be applied to other treatments requiring coordinated delivery of multiple pharmacological agents.

The regeneration of skin appendages including hair follicles (HF), sweat glands (SwG), and sebaceous glands (SeG) is the prerequisite for functional skin repair. However, it is far from being done that how to induce in situ multiple skin appendage regeneration (MSAR) during wound healing. LGR6+ epidermal stem cells (EpSC) have been reported to generate all skin cell lineages. Given the advantages of biomaterials for tissue repair and their influence on cellular behavior that may regulate cell reprogramming, we developed a cell-reprogrammed three lineage-driven biomimetic device (TLBD) by using liposome nanoparticle drug delivery system, photo-responsive hyaluronic acid shell, positively charged polyamide and epidermal cell recruitment factor modification, microfluidic and photo-crosslinking techniques. The LGR6+ EpSC-activating chemical cocktail was the active center of TLBD, and polyamide for a positive charge that made TLBD match the wound electric fields. In vitro and in vivo studies demonstrated that TLBD can efficiently recruit endogenous epidermal cells and activate the LGR6+ EpSC property, prompting their response to wound microenvironment to differentiate into HF, SwG, and SeG lineages, thus facilitating re-epithelialization, wound healing and in situ MSAR. As a novel biomaterial used for in situ skin reprogramming, TLBD may have the great potential for functionally recapitulating damaged skin.

Loss of sweat glands (SwGs) commonly associated with extensive skin defects is a leading cause of hyperthermia and heat stroke. In vivo tissue engineering possesses the potential to take use of the body natural ability to regenerate SwGs, making it more conducive to clinical translation. Despite recent advances in regenerative medicine, reconstructing SwG tissue with the same structure and function as native tissue remains challenging. Elucidating the SwG generation mechanism and developing biomaterials for in vivo tissue engineering is essential for understanding and developing in vivo SwG regenerative strategies. Here, we outline the cell biology associated with functional wound healing and the characteristics of bioactive materials. We critically summarize the recent progress in bioactive material-based cell modulation approaches for in vivo SwG regeneration, including the recruitment of endogenous cells to the skin lesion for SwG regeneration and in vivo cellular reprogramming for SwG regeneration. We discussed the re-establishment of microenvironment via bioactive material-mediated regulators. Besides, we offer promising perspectives for directing in situ SwG regeneration via bioactive material-based cell-free strategy, which is a simple and effective approach to regenerate SwG tissue with both fidelity of structure and function. Finally, we discuss the opportunities and challenges of in vivo SwG regeneration in detail. The molecular mechanisms and cell fate modulation of in vivo SwG regeneration will provide further insights into the regeneration of patient-specific SwGs and the development of potential intervention strategies for gland-derived diseases.

Functional appendage regeneration is essential for skin rehabilitation, but it has always failed by current existing healing approaches, owing to their inefficacy in preventing disfiguring scars. In this study, a novel regeneration-directing artificial skin (RDAS) system is presented, which is based on the rational design of multi-layered hydrogels that closely mimic natural skin matrices. By leveraging the programmability and architectural rigidity of DNA components, without the need for exogenous cell transplantation, such RDAS effectively minimizes tissue fibrosis by accurately guiding the regenerative process in wound fibroblasts, enabling rapid scarless wound repair, restoration of dermal function, and successful in situ regeneration of multiple appendages, such as hair follicles (HFs), sebaceous glands (SGs), and sweat glands (SwGs). Therefore, the RDAS offers a cell-free antiscarring therapeutic strategy for regenerative wound healing, resulting in improved outcomes. This innovative approach holds great potential for future clinical applications and burn rehabilitation.

The scar repair inevitably causes damage of skin function and loss of skin appendages such as hair follicles (HF). It is of great challenge in wound repair that how to intervene in scar formation while simultaneously remodeling HF niche and inducing in situ HF regeneration. Here, chemical reprogramming techniques are used to identify a clinically chemical cocktail (Tideglusib and Tamibarotene) that can drive fibroblasts toward dermal papilla cell (DPC) fate. Considering the advantage of biomaterials in tissue repair and their regulation in cell behavior that may contributes to cellular reprogramming, the artificial HF seeding (AHFS) hydrogel microspheres, inspired by the natural processes of "seeding and harvest", are constructed via using a combination of liposome nanoparticle drug delivery system, photoresponsive hydrogel shell, positively charged polyamide modification, microfluidic and photocrosslinking techniques. The identified chemical cocktail is as the core nucleus of AHFS. In vitro and in vivo studies show that AHFS can regulate fibroblast fate, induce fibroblast-to-DPC reprogramming by activating the PI3K/AKT pathway, finally promoting wound healing and in situ HF regeneration while inhibiting scar formation in a two-pronged translational approach. In conclusion, AHFS provides a new and effective strategy for functional repair of skin wounds.

Background:Skin wound is a widespread health problem and brings extraordinary burdens to patients. Exosomes derived from adipose-derived stem cells (ADSC-Exos) are considered promising strategies for repairing skin wounds. E2F1 is a member of the E2F family of transcription factors involved in cell growth and apoptosis. E2F1 deficiency in mice enhances wound healing by improving collagen deposition and angiogenesis. Additionally, E2F1 can regulate the transcription and paracrine activity of multiple miRNAs, which will inevitably reshape the paracrine expression profile of ADSC-Exos. This study aimed to investigate the impact of transcription factor E2F1 deficiency on the functions of ADSC-Exos in promoting wound healing. Methods:First, we obtained ADSCs from subcutaneous adipose tissues of WT and E2F1-/- C57BL/6 mice and separated their exosomes, denoted as ADSCWT-Exos and ADSCE2F1-/--Exos. The wound healing effects of ADSCWT-Exos and ADSCE2F1-/--Exos in full-thickness skin wound models were investigated by wound images, H&E staining, and immunohistochemical staining. For the in vitro study, the abilities of ADSCWT-Exos and ADSCE2F1-/--Exos to promote cell activities, collagen formation, and angiogenesis were evaluated. The potential mechanism by which ADSCE2F1-/--Exos promote wound healing was determined by miRNA sequencing, ChIP‒qPCR, and dual-luciferase assays. Results:ADSCE2F1-/--Exos accelerated wound healing by promoting collagen formation and angiogenesis. As a result, compared with the lower wound healing rate of 30.5% within 7 days in the control group and 42.3% in the ADSCWT-Exo group, ADSCE2F1-/--Exos significantly increased the wound healing rate to 72.5%. In vitro, ADSCE2F1-/--Exos activated the function of fibroblasts and vascular endothelial cells. The loss of E2F1 promoted miR-130b-5p expression in ADSCE2F1-/--Exos through transcriptional regulation. MiRNA high-throughput sequencing identified 12 differently expressed miRNAs between ADSCE2F1-/- and ADSCWT. ADSCE2F1-/--Exos enhanced fibroblast activities via the miR-130b-5p/TGFBR3 axis and TGF-β activation. Conclusion:Our results indicated that ADSCE2F1-/--Exos effectively promoted wound healing by regulating the miR-130b-5p/TGFBR3 axis, thus providing a novel strategy of gene-engineered stem cell exosomes for accelerating wound healing.

The ageing process is a systemic decline from cellular dysfunction to organ degeneration, with more predisposition to deteriorated disorders. Rejuvenation refers to giving aged cells or organisms more youthful characteristics through various techniques, such as cellular reprogramming and epigenetic regulation. The great leaps in cellular rejuvenation prove that ageing is not a one-way street, and many rejuvenative interventions have emerged to delay and even reverse the ageing process. Defining the mechanism by which roadblocks and signaling inputs influence complex ageing programs is essential for understanding and developing rejuvenative strategies. Here, we discuss the intrinsic and extrinsic factors that counteract cell rejuvenation, and the targeted cells and core mechanisms involved in this process. Then, we critically summarize the latest advances in state-of-art strategies of cellular rejuvenation. Various rejuvenation methods also provide insights for treating specific ageing-related diseases, including cellular reprogramming, the removal of senescence cells (SCs) and suppression of senescence-associated secretory phenotype (SASP), metabolic manipulation, stem cells-associated therapy, dietary restriction, immune rejuvenation and heterochronic transplantation, etc. The potential applications of rejuvenation therapy also extend to cancer treatment. Finally, we analyze in detail the therapeutic opportunities and challenges of rejuvenation technology. Deciphering rejuvenation interventions will provide further insights into anti-ageing and ageing-related disease treatment in clinical settings.

Background Nowadays, wound is associated with a complicated repairing process and still represents a significant biomedical burden worldwide. Bone marrow mesenchymal stem cells (BMSCs) possess multidirectional differentiation potential and secretory function, emerging as potential cellular candidates in treating wounds. Ascorbic acid 2-glucoside (AA2G) is a well-known antioxidant and its function in BMSC-promoting wound healing is worth exploring. Methods The in vitro cell proliferation, migration, and angiogenesis of BMSCs and AA2G-treated BMSCs were detected by flow cytometry, EDU staining, scratch assay, transwell assay, and immunofluorescence (IF). Besides, the collagen formation effect of AA2G-treated BMSCs conditioned medium (CM) on NIH-3T3 cells was evaluated by hydroxyproline, qRT-PCR and IF staining detection. Next, in the wound healing mouse model, the histological evaluation of wound tissue in PBS, BMSCs, and AA2G-treated BMSCs group were further investigated. Lastly, western blot and ELISA were used to detect the expression levels of 5-hmc, TET2 and VEGF protein, and PI3K/AKT pathway activation in BMSCs treated with or without AA2G. Results The in vitro results indicated that AA2G-treated BMSCs exhibited stronger proliferation and improved the angiogenesis ability of vascular endothelial cells. In addition, the AA2G-treated BMSCs CM enhanced migration and collagen formation of NIH-3T3 cells. In vivo, the AA2G-treated BMSCs group had a faster wound healing rate and a higher degree of vascularization in the new wound, compared with the PBS and BMSCs group. Moreover, AA2G preconditioning might enhance the demethylation process of BMSCs by regulating TET2 and up-regulating VEGF expression by activating the PI3K/AKT pathway. Conclusions AA2G-treated BMSCs promoted wound healing by promoting angiogenesis and collagen deposition, thereby providing a feasible strategy to reinforce the biofunctionability of BMSCs in treating wounds.

BackgroundTumors in the central and nipple portion (TCNP) are associated with poor prognosis and aggressive clinicopathological characteristics. The availability and safety of postmastectomy reconstruction in breast cancer patients with TCNP have still not been deeply explored. It is necessary to investigate whether reconstruction is appropriate for TCNP compared with non-reconstruction therapy in terms of survival outcomes.MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) database, we enrolled TCNP patients diagnosed between the years 2010 and 2016. The propensity score matching (PSM) technique was applied to construct a matched sample consisting of pairs of non-reconstruction and reconstruction groups. Survival analysis was performed with the Kaplan–Meier method. Univariate and multivariate Cox proportional hazard models were applied to estimate the factors associated with breast cancer-specific survival (BCSS) and overall survival (OS).ResultsIn the overall cohort, a total of 6,002 patients were enrolled. The patients in the reconstruction group showed significantly better BCSS (log-rank, p < 0.01) and OS (log-rank, p < 0.01) than those in the non-reconstruction group (832 patients) after PSM. However, the multivariate Cox regression model revealed that breast reconstruction was not associated with worse BCSS and OS of TCNP patients.ConclusionOur study provided a new perspective showing that breast reconstruction did not affect the survival and disease prognosis in the cohort of TCNP patients from SEER databases, compared with non-reconstruction. This finding provides further survival evidence supporting the practice of postmastectomy reconstruction for suitable TCNP patients, especially those with a strong willingness for breast reconstruction.

脂肪干细胞外泌体作为细胞间通讯介质，在整形美容领域日益受到关注。脂肪干细胞外泌体通过多种机制在皮肤、骨、软组织修复与再生的组织工程、创面与瘢痕处理、肥胖和乳腺癌等方面有重要作用；并可广泛用于皮肤的抗衰老治疗、创面与瘢痕的修复、皮肤炎症治疗、骨与软骨组织的修复、肥胖症防治、乳房整形和重建等整形美容相关领域，在未来的治疗应用中具有广阔的前景。

Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is an uncommon type of T-cell lymphoma. Although with a low incidence, the epidemiological data raised the biosafety and health concerns of breast reconstruction and breast augmentation for BIA-ALCL. Emerging evidence confirms that genetic features, bacterial contamination, chronic inflammation, and textured breast implant are the relevant factors leading to the development of BIA-ALCL. Almost all reported cases with a medical history involve breast implants with a textured surface, which reflects the role of implant surface characteristics in BIA-ALCL. With this review, we expect to highlight the most significant features on etiology, pathogenesis, diagnosis, and therapy of BIA-ALCL, as well as we review the physical characteristics of breast implants and their potential pathogenic effect and hopefully provide a foundation for optimal choice of type of implant with minimal morbidity.

脂肪移植是整形外科领域一种成熟的填充技术，越来越多地应用于组织填充、面部年轻化、毛发再生等重建和美容手术中。深入了解移植后脂肪细胞的生物学特性，尤其是脂肪相关干细胞分化、血供状态、代谢水平等，对提高脂肪移植存活率有重要意义，促进脂肪移植技术的临床应用。

Abstract Fat transplantation is widely used for soft‐tissue filling and wound repair. Owing to the biological changes in adipocytes in some metabolic diseases, allograft fat can provide a better source of donor fat than autologous fat. Fingolimod (FTY720) possesses a powerful immunomodulatory function. This study aimed to investigate the protective effect of FTY720 in allogeneic fat transplantation. C57BL/6J mice that received allografts were randomly divided into two groups and treated with saline and FTY720, respectively. Fat graft samples were obtained at 1, 6, and 20 weeks posttransplantation. Graft volumes, graft structure, and immune cells were estimated using histological examination, immunohistochemistry, staining immunofluorescence (IF), and quantitative real‐time polymerase chain reaction (qRT‐PCR). Inflammatory cytokine mRNA expression in grafts was detected by qRT‐PCR. FTY720 treatment significantly enhanced allograft retention, structural integrity, and neovascularization, thereby demonstrating the potential of FTY720 in improving graft survival. Further IF staining showed that FTY720 increased regulatory T cell infiltration and reduced macrophage infiltration to some extent. FTY720 treatment also enhanced the expression of the anti‐inflammatory cytokines interleukin (IL)‐4 and IL‐10 and weakened the expression of the pro‐inflammatory cytokines TNF‐α and IL‐6. Furthermore, FTY720 treatment upregulated the expression of CD31 positive cells. This study demonstrated the potential efficacy of FTY720 in improving the graft survival rate of syngeneic fat allograft models, possibly by suppressing immune rejection and promoting angiogenesis. Therefore, this study offers key insights into the potential application of a drug‐assisted strategy to prolong allograft fat survival.

As one of the most frequently occurring malignancies in women, breast cancer (BC) is still an enormous threat to women all over the world. The high mortality rates in BC patients are associated with BC recurrence, metastatic progression to distant organs, and therapeutic resistance. Circular RNAs (circRNAs), belonging to the non-coding RNAs (ncRNAs), are connected end to end to form covalently closed single-chain circular molecules. CircRNAs are widely found in different species and a variety of human cells, with the features of diversity, evolutionary conservation, stability, and specificity. CircRNAs are emerging important participators in multiple diseases, including cardiovascular disease, inflammation, and cancer. Recent studies have shown that circRNAs are involved in BC progress by regulating gene expression at the transcriptional or post-transcriptional level via binding to miRNAs then inhibiting their function, suggesting that circRNAs may be potential targets for early diagnosis, treatment, and prognosis of BC. Herein, in this article, we have reviewed and summarized the current studies about the biogenesis, features, and functions of circRNAs. More importantly, we emphatically elucidate the pivotal functions and mechanisms of circRNAs in BC growth, metastasis, diagnosis, and drug resistance. Deciphering the complex networks, especially the circRNA-miRNA target gene axis, will endow huge potentials in developing therapeutic strategies for combating BC.

BACKGROUND:N6-methyladenosine (m6A), the most abundant and reversible modification of mRNAs in eukaryotes, plays pivotal role in breast cancer (BC) tumorigenesis and progression. Circular RNAs (circRNAs) can act as tumor promoters or suppressors by microRNA (miRNA) sponges in BC. However, the underlying mechanism of circRNAs in BC progression via regulating m6A modulators remains unclear.METHODS:Prognostic m6A RNA methylation regulators were identified in 1065 BC patients from The Cancer Genome Atlas (TCGA) project. Differentially expressed (DE) miRNAs and DE circRNAs were identified between BC and normal samples in TCGA and GSE101123, respectively. MiRNA-mRNA interactive pairs and circRNA-miRNA interactive pairs were verified by MiRDIP and Circular RNA Interactome. GSEA, KEGG, and ssGSEA were executed to explore the potential biological and immune functions between HNRNPC-high and HNRNPC-low expression groups. qRT-PCR and Western blot were used to quantify the expression of HNRNPC and circBACH2 in MCF-7 and MDA-MB-231 cells. The proliferation of BC cells was assessed by CCK-8 and EdU assay.RESULTS:2 m6A RNA methylation regulators with prognostic value, including HNRNPC and YTHDF3, were identified in BC patients. Then, the regulatory network of circRNA-miRNA-m6A modulators was constructed, which consisted of 2 DE m6A modulators (HNRNPC and YTHDF3), 12 DE miRNAs, and 11 DE circRNAs. Notably, BC patients with high expression of HNRNPC and low expression of hsa-miR-944 were correlated with late clinical stages and shorter survival times. Besides, the results from the KEGG inferred that the DE HNRNPC was associated with the MAPK signaling pathway in BC. Moreover, the circBACH2 (hsa_circ_0001625) was confirmed to act as hsa-miR-944 sponge to stimulate HNRNPC expression to promote BC cell proliferation via MAPK signaling pathway, thus constructing a circBACH2/hsa-miR-944/HNRNPC axis in BC.CONCLUSIONS:Our findings decipher a novel circRNA-based m6A regulatory mechanism involved in BC progression, thus providing attractive diagnostic and therapeutic strategies for combating BC.

Breast cancer (BC) is the most frequently invasive malignancy and the leading cause of tumor-related mortality among women worldwide. Cancer metastasis is a complex, multistage process, which eventually causes tumor cells to colonize and grow at the metastatic site. Distant organ metastases are the major obstacles to the management of advanced BC patients. Notably, exosomes are defined as specialized membrane-enclosed extracellular vesicles with specific biomarkers, which are found in a wide variety of body fluids. Recent studies have demonstrated that exosomes are essential mediators in shaping the tumor microenvironment and BC metastasis. The transferred tumor-derived exosomes modify the capability of invasive behavior and organ-specific metastasis in recipient cells. BC exosomal components, mainly including noncoding RNAs (ncRNAs), proteins, lipids, are the most investigated components in BC metastasis. In this review, we have emphasized the multifaceted roles and mechanisms of tumor-derived exosomes in BC metastasis based on these important components. The underlying mechanisms mainly include the invasion behavior change, tumor vascularization, the disruption of the vascular barrier, and the colonization of the targeted organ. Understanding the significance of tumor-derived exosomal components in BC metastasis is critical for yielding novel routes of BC intervention.

Autologous fat transplantation is widely regarded as an increasingly popular method for augmentation or reshaping applications in soft tissue defects. Although the fat transplantation is of simple applicability, low donor site morbidity and excellent biocompatibility, the clinical unpredictability and high resorption rates of the fat grafts remain an inevitable problem. In the sites of fat transplantation, the most essential components are the adipocyte and adipose-derived stem cells (ADSCs). The survival of adipocytes is the direct factor determining fat retention. The efficacy of fat transplantation is reduced by fat absorption and fibrosis due to the inadequate blood flow, adipocyte apoptosis and fat necrosis. ADSCs, a heterogeneous mixture of cells in adipose tissue, are closely related to tissue survival. ADSCs exhibit the ability of multilineage differentiation and remarkable paracrine activity, which is crucial for graft survival. This article will review the recent existing research on the mechanisms of adipocytes and ADSCs in fat transplantation, especially including adipocyte apoptosis, mature adipocyte dedifferentiation, adipocyte browning, ADSCs adipogenic differentiation and ADSCs angiogenesis. The in-depth understanding of the survival mechanism will be extremely valuable for achieving the desired filling effects.

Obesity is associated with energy metabolic disturbance and is caused by long-term excessive energy storage in white adipose tissue (WAT). The WAT browning potentially reduces excessive energy accumulation, contributing an attractive target to combat obesity. As a pivotal regulator of cell growth, the transcription factor E2F1 activity dysregulation leads to metabolic complications. The regulatory effect and underlying mechanism of E2F1 knockout on WAT browning, have not been fully elucidated. To address this issue, in this study, the in vivo adipose morphology, mitochondria quantities, uncoupling protein 1 (UCP-1), autophagy-related genes in WAT of wild-type (WT) and E2F1(-/-) mice were detected. Furthermore, we evaluated the UCP-1, and autophagy-related gene expression in WT and E2F1(-/-) adipocyte in vitro. The results demonstrated that E2F1 knockout could increase mitochondria and UCP-1 expression in WAT through autophagy suppression in mice, thus promoting WAT browning. Besides, adipocytes lacking E2F1 showed upregulated UCP-1 and downregulated autophagy-related genes expression in vitro. These results verified that E2F1 knockout exerted effects on inducing mice WAT browning through autophagy inhibition in vivo and in vitro. These findings regarding the molecular mechanism of E2F1-modulated autophagy in controlling WAT plasticity, provide a novel insight into the functional network with the potential therapeutic application against obesity.

Exposure to the external environment may lead to instability and dysfunction of the skin, resulting in refractory wound, skin aging, pigmented dermatosis, hair loss, some immune-mediated dermatoses, and connective tissue diseases. Nowadays, many skin treatments have not achieved a commendable balance between medical recovery and cosmetic needs. Exosomes are cell-derived nanoscale vesicles carrying various biomolecules, including proteins, nucleic acids, and lipids, with the capability to communicate with adjacent or distant cells. Recent studies have demonstrated that endogenic multiple kinds of exosomes are crucial orchestrators in shaping physiological and pathological development of the skin. Besides, exogenous exosomes, such as stem cell exosomes, can serve as novel treatment options to repair, regenerate, and rejuvenate skin tissue. Herein, we review new insights into the role of endogenic and exogenous exosomes in the skin microenvironment and recent advances in applications of exosomes related to dermatology and cutaneous medical aesthetics. The deep understanding of the mechanisms by which exosomes perform biological functions in skin is of great potential to establish attractive therapeutic methods for the skin.

Autologous fat grafting (AFG) is widely regarded as an important method for breast reconstruction after mastectomy among breast cancer (BC) patients. FTY720 has been proved to affect macrophage polarization and improve the sensitivity of postoperative BC treatment. This study aimed to explore FTY720 function and underlying mechanism in fat transplantation. The C57BL/6 J mice that received AFG were randomly divided into two groups treated with saline and FTY720, respectively. The fat graft samples were obtained at week 1, 2, 4, and 12 post-transplantation. Graft volumes, graft structures, M2 macrophages, and STAT3 protein expression were estimated by histological examination, immunofluorescence, flow cytometry, and western blot, respectively. In vitro, mouse preadipocytes were stimulated with FTY720 treated-M2 macrophages conditioned medium (FTY720-M2-CM) to evaluate the adipogenesis effect. The level of adipogenic mRNA expression in preadipocytes was detected by RT-PCR. The in vivo results showed that FTY720 treatment significantly enhanced the fat graft retention, structure integrity, and neovascularization, indicating the potential of FTY720 in improving graft survival. The histology results showed more polarized M2 macrophage presented in the FTY720 group. In the in vitro assay, after FTY720-M2-CM treatment, the 3T3-L1 preadipocytes showed the increased triglyceride content and adipogenic mRNA expression, including FABP4, C/EBP-α, Adipoq, and PPARγ. Furthermore, FTY720 treatment up-regulated the expression level of M2 biomarker CD206, Arg-1, Fizz-1, which could be weakened by the STAT3 inhibitor. Together, this study confirmed the potential efficacy of FTY720 in improving graft survival in the AFG model, possibly mediated by polarizing macrophages to M2 type through activating the STAT3 pathway.