Osteoarthritis (OA) is a degenerative joint disease that significantly impacts quality of life and poses a growing economic burden. Adipose tissue-derived therapies, including both cell-based and cell-free products, have shown promising potential in promoting cartilage repair, modulating inflammation, and improving joint function. Recent studies and clinical trials have demonstrated their regenerative effects, highlighting their feasibility as a novel treatment approach for OA. This review summarises the therapeutic mechanisms and latest advancements in adipose tissue-derived therapies, providing insights into their clinical applications and future prospects.

Mesenchymal stem cells (MSCs) and their secretome have significant potential in promoting hair follicle development. However, the effects of MSC therapy have been reported to vary due to their heterogeneous characteristics. Different sources of MSCs or culture systems may cause heterogeneity of exosomes.

To define the potential of human adipose-derived MSC exosomes (hADSC-Exos) and human umbilical cord-derived MSC exosomes (hUCMSC-Exos) for improving dermal papillary cell proliferation in androgenetic alopecia.

We conducted liquid chromatography-mass spectrometry proteomic analysis of hADSC-Exos and hUCMSC-Exos. Liquid chromatography-mass spectrometry suggested that hADSC-Exos were related to metabolism and immunity. Additionally, the hADSC-Exo proteins regulated the cell cycle and other 9 functional groups.

We verified that hADSC-Exos inhibited glycogen synthase kinase-3β expression by activating the Wnt/β-catenin signaling pathway via cell division cycle protein 42, and enhanced dermal papillary cell proliferation and migration. Excess dihydrotestosterone caused androgenetic alopecia by shortening the hair follicle growth phase, but hADSC-Exos reversed these effects.

This study indicated that hair development is influenced by hADSC-Exo-mediated cell-to-cell communication via the Wnt/β-catenin pathway.

Androgenetic alopecia (AGA), a leading cause of progressive hair loss, affects up to 50% of males aged 50 years, causing significant psychological burden. Current treatments, such as anti-androgen drugs and minoxidil, show heterogeneous effects, even with long-term application. Meanwhile, the large-scale adoption of other adjuvant therapies has been slow, partly due to insufficient mechanistic evidence. A major barrier to developing better treatment for AGA is the incomplete understanding of its pathogenesis. The predominant academic consensus is that AGA is caused by abnormal expression of androgens and their receptors in individuals with a genetic predisposition. Emerging evidence suggests the contributing role of factors such as immune responses, oxidative stress, and microbiome changes, which were not previously given due consideration. Immune-mediated inflammation and oxidative stress disrupt hair follicles' function and damage the perifollicular niche, while scalp dysbiosis influences local metabolism and destabilizes the local microenvironment. These interconnected mechanisms collectively contribute to AGA pathogenesis. These additional aspects enhance our current understanding and confound the conventional paradigm, bridging the gap in developing holistic solutions for AGA. In this review, we gather existing evidence to discuss various etiopathogenetic factors involved in AGA and their possible interconnections, aiming to lay the groundwork for the future identification of therapeutic targets and drug development. Additionally, we summarize the advantages and disadvantages of AGA research models, ranging from cells and tissues to animals, to provide a solid basis for more effective mechanistic studies.

Androgenetic alopecia (AGA) continues to pose a significant challenge due to the paucity of effective therapeutic options. Upon lysis, platelet-rich plasma (PRP) releases numerous growth factors (GFs), which facilitate tissue reconstruction and hair regeneration. However, concerns such as infection, bleeding, local erythema, and patient anxiety associated with injections have substantially diminished patient acceptance. To address these issues, we developed a microneedle (MN) system loaded with PRP lysate (PL), termed PL-MN, designed to deliver GFs transdermal to sites of hair loss without inducing significant discomfort. The PL-MN not only exhibits a well-defined needle structure but also demonstrates excellent in vivo penetration and external transdermal efficacy. Upon skin penetration, the needle matrix rapidly dissolves, releasing GFs directly to the target site. In animal tests, the PL-MN shows synergistic effects by orchestrating an upregulation in the expression of Ki67 and CD31, which collectively foster cell proliferation and migration, thereby facilitating the expedited progression of hair follicles (HFs) into the anagen phase and promoting peripheral angiogenesis. Compared with minoxidil, the first-line clinical drug for treating AGA (administered once per day, 20 times in total), the PL-loaded MN could induce hair regeneration in mice with a lower frequency of administration (once every 3 days, 5 times in total). Consequently, such a safe and GFs-releasing MNs patch shows great potential for clinical AGA treatment.

Preimplantation embryos in vivo are exposed to various growth factors in the female reproductive tract that are absent in in vitro embryo culture media. Cell-free fat extract exerts antioxidant, anti-ageing, and ovarian function-promoting effects. However, its effects on embryo quality are yet to be investigated.

We assessed the effect of cell-free fat extract supplementation on embryo culture using a naturally ageing mouse model. We assessed the model's efficacy in influencing embryo development and pregnancy rates in older women with in vitro fertilization failure. In addition, we performed immunofluorescence staining, multiplex immunoassay, whole-genome amplification and DNA sequencing, time-lapse embryo monitoring, and in vitro experiments.

Cell-free fat extract-supplemented media has a suitable osmolarity and pH and contains high levels of bioactive growth factors. Cell-free fat extract promoted embryo development and implantation in aged mice, probably by increasing embryo growth rate, inhibiting cell apoptosis, and promoting blastocyst adhesion. Clinical results showed that the cell-free fat extract group had significantly higher rates of the day 3 available and high-quality embryos than the control group, and the rate of usable embryos tended to be higher in the cell-free fat extract group. Furthermore, implantation and clinical pregnancy rates improved in the cell-free fat extract group than in the control group.

Our study implies that cell-free fat extract supplementation can promote embryo development and clinical outcomes and may serve as a rescue strategy for older women with in vitro fertilization failure.

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.

Formation of adequate vascular network within engineered three-dimensional (3D) tissue substitutes postimplantation remains a major challenge for the success of biomaterials-based tissue regeneration. To better mimic the in vivo angiogenic and vasculogenic processes, nowadays increasing attention is given to the strategy of functionalizing biomaterial scaffolds with multiple bioactive agents. Aimed at engineering electrospun biomimicking fibers with pro-vasculogenic capability, this study was proposed to functionalize electrospun fibers of polycaprolactone/gelatin (PCL/GT) by cell-free fat extract (CEFFE or FE), a newly emerging natural "cocktail" of cytokines and growth factors extracted from human adipose tissue. This was achieved by having the electrospun PCL/GT fiber surface coated with polydopamine (PDA) followed by PDA-mediated immobilization of FE to generate the pro-vasculogenic fibers of FE-PDA@PCL/GT. It was found that the PDA-coated fibrous mat of PCL/GT exhibited a high FE-loading efficiency (∼90%) and enabled the FE to be released in a highly sustained manner. The engineered FE-PDA@PCL/GT fibers possess improved cytocompatibility, as evidenced by the enhanced cellular proliferation, migration, and RNA and protein expressions (e.g., CD31, vWF, VE-cadherin) in the human umbilical vein endothelial cells (huvECs) used. Most importantly, the FE-PDA@PCL/GT fibrous scaffolds were found to enormously stimulate tube formation in vitro, microvascular development in the in ovo chick chorioallantoic membrane (CAM) assay, and vascularization of 3D construct in a rat subcutaneous embedding model. This study highlights the potential of currently engineered pro-vasculogenic fibers as a versatile platform for engineering vascularized biomaterial constructs for functional tissue regeneration.