Adipose-derived stem cells (ADSCs) are a type of stem cell found in adipose tissue with the capacity to differentiate into multiple lineages, including osteoblasts. The differentiation of ADSCs into osteoblasts underlies osteogenic and pathological cellular basis in osteoporosis, bone damage and repair.

Focused on ADSCs osteogenic differentiation, we conducted mRNA, microRNA expression and bioinformatics analysis, including gene differential expression, time series-based trend analysis, functional enrichment, and generates potential nuclear activating miRNAs (NamiRNA) regulatory network. The screened mRNAs in NamiRNA regulatory network were validated with correlation analysis.

The NamiRNA Regulatory Network reveals 4 mRNAs (C12orf61, MIR31HG, NFE2L1, and PCYOX1L) significantly downregulated in differentiated group and may be associated with ADSCs stemness. Furthermore, the significantly upregulated 10 genes (ACTA2, TAGLN, LY6E, IFITM3, NGFRAP1, TCEAL4, ATP5C1, CAV1, RPSA, and KDELR3) were significantly enriched in osteogenic-related pathways, and negatively correlated with ADSCs cell stemness in vitro.

These findings uncover potential genes related to ADSCs osteogenic differentiation, and provide theoretical basis for underlying ADSCs osteogenic differentiation and related diseases.

Burns are common injuries, but their treatment remains challenging due to the complex nature of the wound healing process. Burn wounds are classified into different categories based on their size and depth. Treatment modalities vary significantly across these categories, primarily focusing on the inflammation, proliferation, and remodeling phases of burn wound healing. This review summarizes current research on various approaches to enhance burn wound recovery, including advancements in wound dressings, the use of platelet-rich plasma, stem cells, their soluble factors primarily in the form of secretomes or extracellular vesicles, and nano-technologies. Additionally, advancements in modernized traditional medicine are discussed to give a new aspect for burn wound healing. This review also summarizes the barriers in translating bench research to clinical practice in burn wound treatment methods. For an effective translation, researchers and industrial partners should work more closely, while regulatory bodies should streamline the approval procedure.

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by vasculopathy and tissue fibrosis affecting the skin and internal organs. Genetic and environmental factors influence susceptibility, severity, and onset. Current treatments are limited and not always effective, leading researchers to investigate new approaches, such as the use of adipose-derived mesenchymal stem cells (ADSCs) through fat grafting. This review seeks to understand how ADSCs may impact the development and progression of SSc, with a particular focus on how these cells could alter immune responses and reduce fibrosis. ADSCs have been found to affect various immune cells, including T cells, B cells, macrophages, and dendritic cells, by releasing cytokines, chemokines, and growth factors. These interactions generally suppress inflammation and promote a regulatory immune environment. Additionally, ADSCs can influence the extracellular matrix, helping to prevent fibrosis through signaling molecules like exosomes. ADSCs show promise as a treatment for SSc due to their ability to modulate the immune system and reduce fibrosis. Early clinical studies are encouraging, but more research is needed to fully understand how they work and to develop effective treatment protocols.

Dermal white adipose tissue (dWAT), distinguished by its origin from cells within the dermis and independence from subcutaneous fat tissue, has garnered significant attention for its non-metabolic functions. Characterized by strong communication with other components of the skin, dWAT mediates the proliferation and recruitment of various cell types by releasing adipogenic and inflammatory factors. Here, we focus on the modulatory role of dWAT at different stages during wound healing, highlighting its ability to mediate the adipocyte-to-myofibroblast transition which plays a pivotal role in the physiology and pathology processes of skin fibrosis, scarring, and aging. This review highlights the regulatory potential of dWAT in modulating wound healing processes and presents it as a target for developing therapeutic strategies aimed at reducing scarring and enhancing regenerative outcomes in skin-related disorders.

Stem cell treatment may enhance erectile dysfunction (ED) in individuals with cavernous nerve injury (CNI). Nevertheless, no investigations have directly ascertained the implications of varying amounts of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on ED. We compare the efficacy of three various doses of HUC-MSCs as a therapeutic strategy for ED. Sprague-Dawley rats (total = 175) were randomly allocated into five groups. A total of 35 rats underwent sham surgery and 140 rats endured bilateral CNI and were treated with vehicles or doses of HUC-MSCs (1 × 106 cells, 5 × 106 cells, and 1 × 107 cells in 0.1 ml, respectively). Penile tissues were harvested for histological analysis on 1 day, 3 days, 7 days, 14 days, 28 days, 60 days, and 90 days postsurgery. It was found that varying dosages of HUC-MSCs enhanced the erectile function of rats with bilateral CNI and ED. Moreover, there was no significant disparity in the effectiveness of various dosages of HUC-MSCs. However, the expression of endothelial markers (rat endothelial cell antigen-1 [RECA-1] and endothelial nitric oxide synthase [eNOS]), smooth muscle markers (alpha smooth muscle actin [α-SMA] and desmin), and neural markers (neurofilament [RECA-1] and neurogenic nitric oxide synthase [nNOS]) increased significantly with prolonged treatment time. Masson's staining demonstrated an increased in the smooth muscle cell (SMC)/collagen ratio. Significant changes were detected in the microstructures of various types of cells. In vivo imaging system (IVIS) analysis showed that at the 1st day, the HUC-MSCs implanted moved to the site of damage. Additionally, the oxidative stress levels were dramatically reduced in the penises of rats administered with HUC-MSCs.

Peripheral nerve injuries are common complications in surgical and dental practices, often resulting in functional deficiencies and reduced quality of life. Current treatment choices, such as autografts, have limitations, including donor site morbidity and suboptimal outcomes. Adipose-derived stem cells (ADSCs) have shown assuring regenerative potential due to their accessibility, ease of harvesting and propagation, and multipotent properties. This review investigates the therapeutic potential of ADSCs in peripheral nerve regeneration, focusing on their use in bioengineered nerve conduits and supportive microenvironments. The analysis is constructed on published case reports, organized reviews, and clinical trials from Phase I to Phase III that investigate ADSCs in managing nerve injuries, emphasizing both peripheral and orofacial applications. The findings highlight the advantages of ADSCs in promoting nerve regeneration, including their secretion of angiogenic and neurotrophic factors, support for cellular persistence, and supplementing scaffold-based tissue repair. The regenerative capabilities of ADSCs in peripheral nerve injuries offer a novel approach to augmenting nerve repair and functional recovery. The accessibility of adipose tissue and the minimally invasive nature of ADSC harvesting further encourage its prospective application as an autologous cell source in regenerative medicine. Future research is needed to ascertain standardized protocols and optimize clinical outcomes, paving the way for ADSCs to become a mainstay in nerve regeneration.

A catalytic ROS-scavenging hydrogel (HGel) was developed to enhance the growth factor secretion and the therapeutic efficacy of human adipose-derived stem cells (hADSCs) in inflammatory environments. The HGel is composed of heparin and hyaluronic acid, further functionalized with hemin to endow superoxide dismutase and catalase activities. The functionalization of hemin enables the HGel to effectively scavenge ROS (superoxide and H2O2), thereby protecting encapsulated hADSCs from oxidative stress and maintaining their metabolic activities. As a result, the HGel enhanced growth factor secretion of hADSCs in inflammatory conditions compared to non-functionalized, bare heparin/hyaluronic acid hydrogel (Gel). The therapeutic efficacy of the hADSC-encapsulated HGel (C/HGel) was evaluated in a diabetic wound model. The C/HGel significantly accelerated wound closure, reduced ROS levels, mitigated inflammation, and promoted angiogenesis compared to the hADSC-encapsulated Gel (C/Gel) as well as the HGel itself. The HGel has the potential to be utilized as an excellent cell carrier for stem cell therapy in various inflammatory diseases. Overall, this study demonstrated a strategy of enhancing growth factor secretion from stem cells using catalytic antioxidant hydrogels for superior regenerative effects in cell therapy.

Adipose-derived stem cells (ADSCs) are characterized by their low immunogenicity and unique immunosuppressive properties, providing many opportunities for autologous transplantation in regenerative medicine and plastic surgery. These methods are characterized by low rejection rates and intense stimulation of tissue regeneration. However, procedures during which fat tissue is harvested occur under local anaesthesia. To better understand the effects and mechanisms of anaesthetic compounds in cosmetic and therapeutic procedures, the present study used a mixture of these compounds (0.1% epinephrine, 8.4% sodium bicarbonate, and 4% articaine) and examined their impact on a human adipose-derived stem cell line. The results showed anesthetics' negative, dose-dependent effect on cell viability and proliferation, especially during the first 24 h of incubation. After extending the exposure to 48 and 72 h of incubation, cells adapted to new culture conditions. In contrast, no significant changes were observed in immunophenotype, cell cycle progression, and apoptosis. The results obtained from this study provide information on the effect of the selected mixture of anaesthetics on the characteristics and function of ASC52telo cells. The undesirable changes in the metabolic activity of cells suggest the need to search for new drugs to harvest cells with unaltered properties and higher efficacy in aesthetic medicine treatments.

Skin wound healing is a complicated biological process that mainly occurs in response to injury, burns, or diabetic ulcers. It can also be triggered by other conditions such as dermatitis and melanoma-induced skin cancer. Delayed healing or non-healing after skin injury presents an important clinical issue; therefore, further explorations into the occurrence and development of wound healing at the cellular and molecular levels are necessary. Single-cell sequencing (SCS) is used to sequence and analyze the genetic messages of a single cell. Furthermore, SCS can accurately detect cell expression and gene sequences. The use of SCS technology has resulted in the emergence of new concepts pertaining to wound healing, making it an important tool for studying the relevant mechanisms and developing treatment strategies. This article discusses the application value of SCS technology, the effects of the latest research on skin wound healing, and the value of SCS technology in clinical applications. Using SCS to determine potential biomarkers for wound repair will serve to accelerate wound healing, reduce scar formation, optimize drug delivery, and facilitate personalized treatments.

Skin has strong self-regenerative capacity, while severe skin defects do not heal without appropriate treatment. Therefore, in order to cover the wound sites and hasten the healing process, wound dressings are required. Hydrogels have emerged as one of the most promising candidates for wound dressings because of their hydrated and porous molecular structure. Chitosan (CS) with biocompatibility, oxygen permeability, hemostatic and antimicrobial properties is beneficial for wound treatment and it can generate self-healing hydrogels through reversible crosslinks, from dynamic covalent bonding, such as Schiff base bonds, boronate esters, and acylhydrazone bonds, to physical interactions like hydrogen bonding, electrostatic interaction, ionic bonding, metal-coordination, host-guest interactions, and hydrophobic interaction. Therefore, various chitosan-based self-healing hydrogel dressings have been prepared in recent years to cope with increasingly complex wound conditions. This review's objective is to provide comprehensive information on the self-healing mechanism of chitosan-based hydrogel wound dressings, discuss their advanced functions including antibacterial, conductive, anti-inflammatory, anti-oxidant, stimulus-responsive, hemostatic/adhesive and controlled release properties, further introduce their applications in the promotion of wound healing in two categories: acute and chronic (infected, burn and diabetic) wounds, and finally discuss the future perspective of chitosan-based self-healing hydrogel dressings for wound healing.

Hepatocellular carcinoma (HCC) ranks as the most prevalent of primary liver cancers and stands as the third leading cause of cancer-related deaths. Early-stage HCC can be effectively managed with available treatment modalities ranging from invasive techniques, such as liver resection and thermoablation, to systemic therapies primarily employing tyrosine kinase inhibitors. Unfortunately, these interventions take a significant toll on the body, either through physical trauma or the adverse effects of pharmacotherapy. Consequently, there is an understandable drive to develop novel HCC therapies. Adipose-derived stem cells (ADSCs) are a promising therapeutic tool. Their facile extraction process, coupled with the distinctive immunomodulatory capabilities of their secretome, make them an intriguing subject for investigation in both oncology and regenerative medicine. The factors they produce are both enzymes affecting the extracellular matrix (specifically, metalloproteinases and their inhibitors) as well as cytokines and growth factors affecting cell proliferation and invasiveness. So far, the interactions observed with various cancer cell types have not led to clear conclusions. The evidence shows both inhibitory and stimulatory effects on tumor growth. Notably, these effects appear to be dependent on the tumor type, prompting speculation regarding their potential inhibitory impact on HCC. This review briefly synthesizes findings from preclinical and clinical studies examining the effects of ADSCs on cancers, with a specific focus on HCC, and emphasizes the need for further research.

Adipose tissue injections, a rich source of mesenchymal stem cells, have been successfully used to promote anal fistula healing. This study aimed to investigate the efficacy of adipose tissue injection in treating patients with complex and recurrent fistulas of cryptoglandular origin.

We conducted a prospective, single-center, open-label, non-randomized, interventional clinical trial from January 2020 to December 2022. We enrolled nine patients, who were evaluated after at least 12 months of follow-up. All patients had seton removal, fistula tract excision or curettage, and a mucosal flap if possible or, alternatively, an internal opening suture. We used a commercially available system to collect and process adipose tissue prior to injection. This system allowed the collection, microfragmentation, and filtration of tissue.

Selected cases included six men and three women with a median age of 42 (range 31-55) years. All patients had an extended disease course period, ranging from 3 to 13 (mean 6.6) years, and a history of multiple previous surgeries, including two to eight interventions (a mean of 4.4 per case). All fistulas were high transsphincteric, four cases horseshoe and two cases with secondary suprasphincteric or peri-elevator tract fistulas. Six cases (66%) achieved complete fistula healing at a mean follow-up of 18 (range 12-36) months. Three cases (33.3%) experienced reduced secretion and decreased anal discomfort.

In patients with complex and recurrent fistulas, such as the ones described, many from palliative treatments with setons, the adjuvant injection of adipose tissue might help achieve complete healing or improvement in a significant percentage of cases.

The study protocol was prospectively registered on ClinicalTrials.gov (NCT04750499).

This study aims to investigate the potential of stromal vascular fraction (SVF) for peripheral nerve regeneration.

A scoping review of Scopus and PubMed databases was conducted. Inclusion criteria were human or animal studies exploring the use of SVF for peripheral nerve regeneration. Studies were categorized by assessed outcomes: pain assessment, neural integrity, muscle recovery, and functional recovery. Level of evidence and study quality were assessed.

Nine studies met the inclusion criteria. SVF injection in humans with trigeminal neuropathic pain reduced pain scores from 7.5 ± 1.58 to 4.3 ± 3.28. SVF injection improved sensation in humans with leprosy neuropathy. Repairing transected rat sciatic nerves with SVF-coated nerve autografts improved wet muscle weight ratios (0.65 ± 0.11 vs 0.55 ± 0.06) and sciatic functional index (SFI) scores (-68.2 ± 9.2 vs -72.5 ± 8.9). Repairing transected rat sciatic nerves with SVF-coated conduits increased the ratio of gastrocnemius muscle weights (RGMW) (7-10% improvement), myelinated fibers (1,605 ± 806.2 vs 543.6 ± 478.66), and myelin thickness (5-20% increase). Repairing transected rat facial nerves with SVF-coated conduits improved whisker motion (9.22° ± 0.65° vs 1.90° ± 0.84°) and myelin thickness (0.57 μm ± 0.17 vs 0.45 μm ± 0.14 μm). Repairing transected rat sciatic nerves with SVF-coated nerve allografts improved RGMW (85 vs 50%), SFI scores (-20 to -10 vs -40 to -30), and Basso, Beatie, and Bresnahan locomotor scores (18 vs 15). All metrics mentioned above were statistically significant. The human studies were level 4 evidence due to being case series, while animal studies were the lowest level of evidence.

Despite initial promising results, the low-level evidence from the included studies warrants further investigation.

Adipose-derived stem cells (ADSCs) are promising in regenerative medicine. Their proliferation, survival and activation are influenced by specific signals within their microenvironment, also known as niche. The stem cell niche is regulated by complex interactions between multiple cell types. When transplanted in a specific area, ADSCs can secrete several immunomodulatory factors. At the same time, a tumor microenvironment can influence stem cell behavior, modulating proliferation and their ability to differentiate into a specific phenotype. Whitin this context, we exposed ADSCs to plasma samples derived from human patients diagnosed with prostate cancer (PC), or precancerous lesions (PL), or benign prostatic hyperplasia (BPH) for 4, 7 or 10 days. We then analyzed the expression of main stemness-related markers and cell-cycle regulators. We also measured cytokine production and polyamine secretion in culture medium and evaluated cell morphology and collagen production by confocal microscopy. The results obtained from this study show significant changes in the morphology of ADSCs exposed to plasma samples, especially in the presence of prostate cancer plasma, suggesting important implications in the use of ADSCs for the development of new treatments and application in regenerative medicine.

Adipose tissues in the hypodermis, the crucial stem cell reservoir in the skin and the endocrine organ for the maintenance of skin homeostasis undergo significant changes during skin aging. Dermal white adipose tissue (dWAT) has recently been recognized as an important organ for both non-metabolic and metabolic health in skin regeneration and rejuvenation. Defective differentiation, adipogenesis, improper adipocytokine production, and immunological dissonance dysfunction in dWAT lead to age-associated clinical changes. Here, we review age-related alterations in dWAT across levels, emphasizing the mechanisms underlying the regulation of aging. We also discuss the pathogenic changes involved in age-related fat dysfunction and the unfavorable consequences of accelerated skin aging, such as chronic inflammaging, immunosenescence, delayed wound healing, and fibrosis. Research has shown that adipose aging is an early initiation event and a potential target for extending longevity. We believe that adipose tissues play an essential role in aging and form a potential therapeutic target for the treatment of age-related skin diseases. Further research is needed to improve our understanding of this phenomenon.

Diabetic foot ulcers (DFUs) pose a critical medical challenge, significantly im-pairing the quality of life of patients. Adipose-derived stem cells (ADSCs) have been identified as a promising therapeutic approach for improving wound healing in DFUs. Despite extensive exploration of the mechanical aspects of ADSC therapy against DFU, its clinical applications remain elusive. In this review, we aimed to bridge this gap by evaluating the use and advancements of ADSCs in the clinical management of DFUs. The review begins with a discussion of the classification and clinical management of diabetic foot conditions. It then discusses the current landscape of clinical trials, focusing on their geographic distribution, reported efficacy, safety profiles, treatment timing, administration techniques, and dosing considerations. Finally, the review discusses the preclinical strategies to enhance ADSC efficacy. This review shows that many trials exhibit biases in study design, unclear inclusion criteria, and intervention protocols. In conclusion, this review underscores the potential of ADSCs in DFU treatment and emphasizes the critical need for further research and refinement of therapeutic approaches, with a focus on improving the quality of future clinical trials to enhance treatment outcomes and advance the field of diabetic wound care.

In the realm of large-area trauma flap transplantation, averting ischaemic necrosis emerges as a pivotal concern. Several key mechanisms, including the promotion of angiogenesis, the inhibition of oxidative stress, the suppression of cell death, and the mitigation of inflammation, are crucial for enhancing skin flap survival. Apoptotic bodies (ABs), arising from cell apoptosis, have recently emerged as significant contributors to these functions. This study engineered three-dimensional (3D)-ABs using tissue-like mouse adipose-derived stem cells (mADSCs) cultured in a 3D environment to compare their superior biological effects against 2D-ABs in bolstering skin flap survival. The findings reveal that 3D-ABs (85.74 ± 4.51) % outperform 2D-ABs (76.48 ± 5.04) % in enhancing the survival rate of ischaemic skin flaps (60.45 ± 8.95) % (all p < 0.05). Mechanistically, they stimulated angiogenesis, mitigated oxidative stress, suppressed apoptosis, and facilitated the transition of macrophages from M1 to M2 polarization (all p < 0.05). A comparative analysis of microRNA (miRNA) profiles in 3D- and 2D-ABs identified several specific miRNAs (miR-423-5p-up, miR30b-5p-down, etc.) with pertinent roles. In summary, ABs derived from mADSCs cultured in a 3D spheroid-like arrangement exhibit heightened biological activity compared to those from 2D-cultured mADSCs and are more effective in promoting ischaemic skin flap survival. These effects are attributed to their influence on specific miRNAs.

Introduction  The history of wounds dates back to the evolution of mankind. Throughout the centuries, management modalities of wounds have undergone drastic changes. With the advent of technology, we have multiple options for wound care, but none of them can be called the gold standard of wound care. Autologous fat grafting (AFG) is one of the most routinely performed procedures in aesthetic surgery. Fat grafting has shown beneficial effects in the healing of wounds. The regenerative potential of autologous fat is contributed by the adipose-derived stem cells present within the stromal vascular fraction, which are capable of differentiating into multiple cell types. This study aims to analyze the usefulness of AFG in cutaneous wound healing. Materials and Methods  This prospective, study was conducted in our institute between April 2021 and May 2023. Eighteen patients with nonhealing wounds were included in the study. For assessing wound healing all the patients were first managed with conventional dressing for 2 weeks before surgery. After routine preoperative workup, the procedure was performed under local anesthesia in most cases. Fat was harvested from the lower abdomen and after emulsification, was injected into the edge and floor of the ulcer. The dressing was changed on the third postoperative day and the outcome was assessed. Results  Eighteen patients (M:F ratio 8:1), with a mean age of 35.61 ± 12. 64 years (range 10-65 years), were included in this study. The most common etiology was trauma (44%), others being postop infection (17%), veno-lymphatic ulcer (17%), burns (11%), insect bite (5%), and trophic ulcer (5%). Majority of the wounds (95%) healed without the need for any extra intervention. The mean period taken for complete wound healing was 5.05 weeks. Conclusion  Complete wound healing was achieved in majority of the patients without any complications. We recommend the usage of AFG for nonhealing wounds, as the procedure is relatively simple and can be performed after basic training. Larger-scale randomized controlled trials should be conducted to prove their efficacy in the management of complicated wounds.

Significance: Half of all cancer patients receive radiation therapy as a component of their treatment regimen, and the most common resulting complication is radiation-induced fibrosis (RIF) of the skin and soft tissue. This thickening of the dermis paired with decreased vascularity results in functional limitations and esthetic concerns and poses unique challenges when considering surgical exploration or reconstruction. Existing therapeutic options for RIF of the skin are limited both in scope and efficacy. Cell-based therapies have emerged as a promising means of utilizing regenerative cell populations to improve both functional and esthetic outcomes, and even as prophylaxis for RIF. Recent Advances: As one of the leading areas of cell-based therapy research, adipose-derived stromal cells (ADSCs) demonstrate significant therapeutic potential in the treatment of RIF. The introduction of the ADSC-augmented fat graft has shown clinical utility. Recent research dedicated to characterizing specific ADSC subpopulations points toward further granularity in understanding of the mechanisms driving the well-established clinical outcomes seen with fat grafting therapy. Critical Issues: Various animal models of RIF demonstrated improved clinical outcomes following treatment with cell-based therapies, but the cellular and molecular basis underlying these effects remains poorly understood. Future Directions: Recent literature has focused on improving the efficacy of cell-based therapies, most notably through (1) augmentation of fat grafts with platelet-rich plasma and (2) the modification of expressed RNA through epitranscriptomics. For the latter, new and promising gene targets continue to be identified which have the potential to reverse the effects of fibrosis by increasing angiogenesis, decreasing inflammation, and promoting adipogenesis.

Circular RNAs (circRNAs) have been identified as important regulators in different developmental processes and disease pathogenesis. The loop structure of circRNAs makes them very stable in different conditions and microenvironments. circRNAs can affect microRNA (miRNA) and RNA binding protein (RBP) activity, encode functional proteins and regulate gene transcription. Recently, two circNFIX variants derived from the same gene, the Nuclear Factor I X (NFIX) gene, were determined as participants in the pathological processes of various diseases such as heart diseases and cancers. Both circNFIX variants are exonic circular RNAs and mainly function by sponging miRNAs. In this review, we summarize the current knowledge on circRNAs, elucidate the origins and properties of two circNFIX variants, explore the roles of two circNFIX variants in different diseases, and present clinical perspectives.

Objective: A few studies have focused on the quality of life (QoL) of patients with chronic non-responsive pressure skin ulcers. The aim of this study was to assess how correct treatment (advanced wound care [AWC] dressings alone or vacuum assisted closure [VAC] therapy alone) changes the QoL of these patients. Approach: One hundred six patients with chronic non-responsive pressure skin ulcers, who had previously used galenic dressings, applied without proper therapeutic indication, were included in this study. We administered the WOUND-Q, at time 0 and after 1 month of appropriate therapy, to assess patient-reported outcome measures. Group 1 consisted of 30 patients treated with advanced dressings, Group 2: 22 patients treated with VAC therapy, and Group 3: 30 patients continuing conventional galenic dressings (Control group). Statistical analysis allowed us to analyze QoL changes over time and to compare WOUND-Q Group 1 and 2 deltas with those of Group 3. The study followed the STROBE statement. Results and Innovation: In all the scales evaluated (Assessment, Drainage, Smell, Life impact, Psychological, Social, Sleep and Dressing), there were significant improvements in mean values for Groups 1 and 2. Kruskal-Wallis tests with Dunn's multiple-comparisons tests and Brown-Forsythe and Welch Analysis of Variance tests demonstrated significant differences between deltas of Group 1 and Group 2 compared with those of Group 3 for most scales analyzed. Conclusions: Administration of the WOUND-Q demonstrated that the application of advanced dressings alone or VAC therapy alone positively affects the QoL of patients with chronic nonresponsive pressure wounds, in comparison with galenic dressings alone. The WOUND-Q has been shown to be a valid tool in studying changes in QoL of these patients.

The combination of cells and biomaterials has become a powerful approach to regenerative medicine in recent years. Understanding the in-vitro interactions between cells and biomaterials is crucial for the success of regenerative medicine.

In this study, we developed an AD-pectin/chitosan/nano-crystalline cellulose scaffold with nano-hydroxy-apatite (n-HAP) and alendronate (ALN). The second step was to evaluate its effect on the immunomodulatory properties and biological behaviors of seeded adipose-derived mesenchymal stem cells (ADSCs) for bone tissue repair.

After preparing and evaluating the characterization tests of the new combined n-HAP scaffold, we established different culture conditions to evaluate ADSC growth on this scaffold with or without ALN. The main assays were MTT assay, RT-PCR, and ELISA.

Our data regarding characterization tests (including SEM, TGA, FTIR, gelation time, swelling ratio, rheology and degradation tests) of ALN-loaded n-HAP scaffold showed the proper stability and good mechanical status of the scaffold. ADSC proliferation and viability increased in the presence of the scaffold compared with other conditions. Moreover, our data demonstrated increased gene expression and protein levels of anti-inflammatory TGF-β, HGF, and IDO cytokines in the presence of the ALN-loaded n-HAP scaffold, indicating the increased immunosuppressive activity of ADSCs in vitro.

This study demonstrates the promising abilities of the ALN-loaded n-HAP scaffold to increase the proliferation, viability, and immunomodulatory capacity of ADSCs, elucidating new aspects of cell-material interactions that can be used for bone tissue regeneration/repair, and paving the path of future research in developing new approaches for MSC- based therapy.

This review comprehensively explores the versatile potential of mesenchymal stem cells (MSCs) with a specific focus on adipose-derived MSCs. Ophthalmic and oculoplastic surgery, encompassing diverse procedures for ocular and periocular enhancement, demands advanced solutions for tissue restoration, functional and aesthetic refinement, and aging. Investigating immunomodulatory, regenerative, and healing capacities of MSCs, this review underscores the potential use of adipose-derived MSCs as a cost-effective alternative from bench to bedside, addressing common unmet needs in the field of reconstructive and regenerative surgery.

Cells and extracts derived from adipose tissue are gaining increasing attention not only in plastic surgery and for aesthetic purposes but also in regenerative medicine. The ability of hyaluronan (HA) to support human adipose stromal cell (hASC) viability and differentiation has been investigated. However, the compatibility of adipose tissue with HA-based formulation in terms of biophysical and rheological properties has not been fully addressed, although it is a key feature for tissue integration and in vivo performance. In this study, the biophysical and biochemical properties of highly concentrated (45 mg/mL) high/low-molecular-weight HA hybrid cooperative complex were assessed with a further focus on the potential application in adipose tissue augmentation/regeneration. Specifically, HA hybrid complex rheological behavior was observed in combination with different adipose tissue ratios, and hyaluronidase-catalyzed degradation was compared to that of a high-molecular-weight HA (HHA). Moreover, the HA hybrid complex's ability to induce in vitro hASCs differentiation towards adipose phenotype was evaluated in comparison to HHA, performing Oil Red O staining and analyzing gene/protein expression of PPAR-γ, adiponectin, and leptin. Both treatments supported hASCs differentiation, with the HA hybrid complex showing better results. These outcomes may open new frontiers in regenerative medicine, supporting the injection of highly concentrated hybrid formulations in fat compartments, eventually enhancing residing staminal cell differentiation and improving cell/growth factor persistence towards tissue regeneration districts.

The application of adult mesenchymal stem cells (MSCs) in the field of tissue regeneration is of increasing interest to the scientific community. In particular, scaffolds and/or hydrogel based on glycosaminoglycans (GAGs) play a pivotal role due to their ability to support the in vitro growth and differentiation of MSCs toward a specific phenotype. Here, we describe different possible approaches to develop GAGs-based biomaterials, hydrogel, and polymeric viscous solutions in order to assess/develop a suitable biomimetic environment. To sustain MSCs viability and promote their differentiation for potential therapeutic applications.

Vascularized composite allotransplantation (VCA), which can effectively improve quality of life, is a promising therapy for repair and reconstruction after face or body trauma. However, intractable issues are associated with VCA, such as the inevitable multiple immunogenicities of different tissues that cause severe rejection, the limited protocols available for clinical application, and the shortage of donor sources. The existing regimens used to extend the survival of patients receiving VCAs and suppress rejection are generally the lifelong application of immunosuppressive drugs, which have side effects. Consequently, studies aiming at tissue engineering methods for VCA have become a topic. In this review, we summarize the emerging therapeutic strategies for tissue engineering aimed to prolong the survival time of VCA grafts, delay the rejection and promote prevascularization and tissue regeneration to provide new ideas for future research on VCA treatment.

Human cartilage tissue remains a challenge for the development of therapeutic options due to its poor vascularization and reduced regenerative capacities. There are a variety of research approaches dealing with cartilage tissue engineering. In addition to different biomaterials, numerous cell populations have been investigated in bioreactor-supported experimental setups to improve cartilage tissue engineering. The concept of the present study was to investigate spider silk cocoons as scaffold seeded with adipose-derived stromal cells (ASC) in a custom-made bioreactor model using cyclic axial compression to engineer cartilage-like tissue. For chemical induction of differentiation, BMP-7 and TGF-β2 were added and changes in cell morphology and de-novo tissue formation were investigated using histological staining to verify chondrogenic differentiation. By seeding spider silk cocoons with ASC, a high colonization density and cell proliferation could be achieved. Mechanical induction of differentiation using a newly established bioreactor model led to a more roundish cell phenotype and new extracellular matrix formation, indicating a chondrogenic differentiation. The addition of BMP-7 and TGF-β2 enhanced the expression of cartilage specific markers in immunohistochemical staining. Overall, the present study can be seen as pilot study and valuable complementation to the published literature.

This study aimed to develop a novel culture method for rat adipose-derived stem cells (rADSC) and evaluate their osteogenic potential. The rADSC cultured in xeno-free culture medium (XF-rADSCs) or conventional culture medium containing fetal bovine serum (FBS-rADSCs) were combined with micropieces of xeno-free recombinant collagen peptide to form 3-dimensional aggregates (XF-rADSC-CellSaic or FBS-rADSC-CellSaic). Both FBS-rADSC and XF-ADSC in CellSaic exhibited multilineage differentiation potential. Compared to FBS-rADSC-CellSaic, XF-rADSC-CellSaic accelerated and promoted osteogenic differentiation in vitro. When transplanted into rat mandibular congenital bone defects, the osteogenically differentiated XF-rADSC-CellSaic induced regeneration of bone tissue with a highly maturated structure compared to FBS-rADSC-CellSaic. In conclusion, XF-rADSC-CellSaic is a feasible 3-dimensional platform for efficient bone formation.

Vascularized composite allotransplantation (VCA) has become a clinical reality in the past two decades. However, its routine clinical applications are limited by the risk of acute rejection, and the side effects of the lifelong immunosuppression. Therefore, there is a need for new protocols to induce tolerance and extend VCA survival. Cell- based therapies have emerged as an attractive strategy for tolerance induction in VCA. This manuscript reviews the current strategies and applications of cell-based therapies for tolerance induction in VCA.

Cellular therapies, including the application of bone marrow cells (BMC), mesenchymal stem cells (MSC), adipose stem cells, regulatory T cells (Treg) cells, dendritic cells and donor recipient chimeric cells (DRCC) show promising potential as a strategy to induce tolerance in VCA. Ongoing basic science research aims to provide insights into the mechanisms of action, homing, functional specialization and standardization of these cellular therapies. Additionally, translational preclinical and clinical studies are underway, showing encouraging outcomes.

Cellular therapies hold great potential and are supported by preclinical studies and clinical trials demonstrating safety and efficacy. However, further research is needed to develop novel cell-based immunosuppressive protocol for VCA.

This study aimed to investigate the effects of a collagen endometrial patch (EM patch) loaded with adipose-derived mesenchymal stem cells (ADSCs) on endometrial regeneration in a rat model with thin endometrium.

Thin endometrium was induced in female rats and divided into treatment groups as outlined: control, group 1(G1), local injection of ADSCs into the uterus, group 2 (G2), an EM patch without ADSCs, group 3 (G3), and an EM patch loaded with ADSCs, group 4 (G4). The rats were euthanized at either two weeks or four weeks after modeling and treatment followed by histological and biochemical analyses to examine the regenerative effects on the injured endometrium.

Transplantation of the ADSC-loaded EM patch significantly promoted endometrial proliferation and increased the luminal epithelial area. Two weeks after treatment, the mean number of von Villebrand factor (vWF)+ or cluster of differentiation (CD) 31+-stained blood vessels was significantly higher in G4 than in G1 and G2. The mRNA and protein expression levels of TGF-β and FGF2 were significantly upregulated in G4 compared to those in the control. G4 exhibited significantly increased LIF mRNA levels and immunoreactivity compared with the other groups at both two weeks and four weeks after treatment. Cell tracking after ADSCs treatment revealed the presence of a substantial number of ADSCs grafted in the uterine tissues of G4, whereas a low number of ADSCs that were focally clustered were present in G2.

Transplantation of EM patches loaded with ADSCs resulted in the histological and biochemical restoration of an injured endometrium. The strategic integration of EM patches and ADSCs holds significant promise as an innovative therapeutic approach for effectively treating impaired endometrial conditions.

Mesenchymal stem cells (MSCs) are pivotal players in tissue repair and hold great promise as cell therapeutic agents for regenerative medicine. Additionally, they play a significant role in the development of various human diseases. Studies on MSC biology have encountered a limiting property of these cells, which includes a low number of passages and a decrease in differentiation potential during in vitro culture. Although common methods of immortalization through gene manipulations of cells are well established, the resulting MSCs vary in differentiation potential compared to primary cells and eventually undergo senescence. This study aimed to immortalize primary adipose-derived MSCs by overexpressing human telomerase reverse transcriptase (hTERT) gene combined with a knockdown of TP53. The research demonstrated that immortalized MSCs maintained a stable level of differentiation into osteogenic and chondrogenic lineages during 30 passages, while also exhibiting an increase in cell proliferation rate and differentiation potential towards the adipogenic lineage. Long-term culture of immortalized cells did not alter cell morphology and self-renewal potential. Consequently, a genetically stable line of immortalized adipose-derived MSCs (iMSCs) was established.

The idea of the anterolateral thoracic musculature in men during the contour procedure is very limited, particularly in terms of surgical techniques that improve its appearance and aesthetics. Therefore, this study aimed to describe a technique of deep definition liposuction with intramuscular grafting of the serratus external oblique muscle complex.

A retrospective case series of a total of 11 cases of male patients aged between 29 and 60 years in the year 2022 is presented. These patients underwent body contouring surgery and subsequently underwent ultrasound-guided intramuscular fat grafting in the serratus external oblique complex. As part of the study, measurements were taken before and immediately after surgery. The data were stored in a database and analyzed with the statistical software SPSS, v23.0.

The patients were aged between 29 and 60 years, with a mean age of 38.3 years (±8.5). All cases had a body mass index of 30. Results were matched preinfiltration and postinfiltration; These results were subjected to statistical validation using the Student t test for related samples, and statistically significant differences were obtained in all the measures tested.

The technique of fat grafting in the oblique-serratus complex allows for increasing muscle thickness. The measurements were made only immediately after the infiltration; it is important in the future to show the long-term follow-up. No adverse events occurred during the study.

With its involvement in cell proliferation, migration and differentiation basic fibroblast growth factor (bFGF) has great potential for tissue engineering purposes. So far, however, clinical translation of soluble bFGF-based therapies is unsuccessful, because the required effective doses are often supraphysiological, which may cause adverse effects. An effective solution is growth factor immobilization, whereby bFGF retains its bioactivity at increased efficacy. Studied carriers include films, solid scaffolds, and particles, as well as natural and synthetic hydrogels. However, these synthetic hydrogels poorly resemble the characteristics of the native extracellular matrix (ECM). In this work, bFGF is covalently conjugated to the synthetic, but highly biocompatible, polyisocyanide-based hydrogel (PIC-bFGF), which closely mimics the architecture and mechanical properties of the ECM. The growth factor conjugation protocol is straightforward and readily extrapolated to other growth factors or proteins. The PIC-bFGF hydrogel shows a prolonged bioactivity up to 4 weeks although no clear effects on the ECM metabolism are observed. Beyond the future potential of the PIC-bFGF hydrogel toward various tissue engineering applications, this work underlines that simple biological conjugation procedures are a powerful strategy to induce additional bioactivity in 3D synthetic cell culture matrices.

Photoaging is a degenerative biological process that affects the quality of life. It is caused by environmental factors including ultraviolet radiation (UVR), deep skin burns, smoking, active oxygen, chemical substances, and trauma. Among them, UVR plays a vital role in the aging process.

With the continuous development of modern medicine, clinical researchers have investigated novel approaches to treat aging. In particular, mesenchymal stem cells (MSCs), non-coding RNAs are involved in various physiological processes have broad clinical application as they have the advantages of convenient samples, abundant sources, and avoidable ethical issues.

This article reviews research progress on five types of stem cell, exosomes, non-coding RNA in the context of photoaging treatment: adipose-derived stem cell, human umbilical cord MSCs, epidermal progenitor cells, keratinocyte stem cells, and hair follicle stem cells (HFSCs). It also includes stem cell related exosomes and their non-coding RNA research.

The results have clinical guiding significance for prevention and control of the onset and development of photoaging. It is found that stem cells secrete cytokines, cell growth factors, non-coding RNA, exosomes and proteins to repair aging skin tissues and achieve skin rejuvenation. In particular, stem cell exosomes and non-coding RNA are found to have significant research potential, as they possess the benefits of their source cells without the disadvantages which include immune rejection and granuloma formation.

Foot deformities and gait abnormalities can result in locally elevated peak pedal pressures or atypical pedal biomechanics. Combined with underlying comorbidities such as neuropathy, stroke, atrophic fat padding and history of ulcerations, this can lead to recurrent ulcerations and pain. Pedal fat grafting (PFG) is a treatment modality that has been shown to reduce peak pressures and accelerate wound healing. This study aimed to investigate the utility of PFG to treat and prevent ulcerations.

We retrospectively analyzed medical history, demographics, wound volume at time of procedure, volume of fat injected, surgical outcomes, and presence of new wounds in 15 patients who underwent PFG at Keck Hospital between 2018 and 2023.

Seventeen feet from 15 patients (63 ± 12 years old, body mass index 30.9 ± 3.1) received PFG with an average volume of fat injected of 10.7 mL and procedure time of 84.6 minutes. At the time of PFG, nine wounds were present on nine feet with an average wound volume of 1.6 ± 2.7 cm3. Average follow-up was 6.9 months (range 1-36 months), with no complications or recurrent ulcerations since the procedure.

PFG is a promising treatment option for reducing peak pedal pressure and preventing ulcer recurrence in patients with various conditions. Further study is warranted for long-term follow-up.

Chronic diabetic wounds remain a globally recognized clinical challenge. They occur due to high concentrations of reactive oxygen species and vascular function disorders. A promising strategy for diabetic wound healing is the delivery of exosomes, comprising bioactive dressings. Metformin activates the vascular endothelial growth factor pathway, thereby improving angiogenesis in hyperglycemic states. However, multifunctional hydrogels loaded with drugs and bioactive substances synergistically promote wound repair has been rarely reported, and the mechanism of their combinatorial effect of exosome and metformin in wound healing remains unclear. Here, we engineered dual-loaded hydrogels possessing tissue adhesive, antioxidant, self-healing and electrical conductivity properties, wherein 4-armed SH-PEG cross-links with Ag⁺, which minimizes damage to the loaded goods and investigated their mechanism of promotion effect for wound repair. Multiwalled carbon nanotubes exhibiting good conductivity were also incorporated into the hydrogels to generate hydrogen bonds with the thiol group, creating a stable three-dimensional structure for exosome and metformin loading. The diabetic wound model of the present study suggests that the PEG/Ag/CNT-M + E hydrogel promotes wound healing by triggering cell proliferation and angiogenesis and relieving peritraumatic inflammation and vascular injury. The mechanism of the dual-loaded hydrogel involves reducing the level of reactive oxygen species by interfering with mitochondrial fission, thereby protecting F-actin homeostasis and alleviating microvascular dysfunction. Hence, we propose a drug-bioactive substance combination therapy and provide a potential mechanism for developing vascular function-associated strategies for treating chronic diabetic wounds.

Purpose: This study aimed to explore the effect of biomaterials with different stiffness on Adipose Derived Mesenchymal Stem Cells (ADSC)-macrophage crosstalk in bone tissue engineering and its role in bone repair. Methods: Biomaterials with Young's modulus of 64 and 0.2 kPa were selected, and the crosstalk between ADSCs and macrophages was investigated by means of conditioned medium treatment and cell co-culture, respectively. Polymerase chain reaction (PCR) and flow cytometry were used to evaluate the polarization of macrophages. Alkaline phosphatase (ALP) and alizarin red staining (ARS) solutions were used to evaluate the osteogenic differentiation of ADSCs. Transwell assay was used to evaluate the chemotaxis of ADSCs and macrophages. Moreover, mass spectrometry proteomics was used to analyze the secreted protein profile of ADSCs of different substrates and macrophages in different polarization states. Results: On exploring the influence of biomaterials on macrophages from ADSCs on different substrates, we found that CD163 and CD206 expression levels in macrophages were significantly higher in the 64-kPa group than in the 0.2-kPa group in conditioned medium treatment and cell co-culture. Flow cytometry showed that more cells became CD163+ or CD206+ cells in the 64-kPa group under conditioned medium treatment or cell co-culture. The Transwell assay showed that more macrophages migrated to the lower chamber in the 64-kPa group. The proteomic analysis found that ADSCs in the 64-kPa group secreted more immunomodulatory proteins, such as LBP and RBP4, to improve the repair microenvironment. On exploring the influence of biomaterials on ADSCs from macrophages in different polarization states, we found that ALP and ARS levels in ADSCs were significantly higher in the M2 group than in the other three groups (NC, M0, and M1 groups) in both conditioned medium treatment and cell co-culture. The Transwell assay showed that more ADSCs migrated to the lower chamber in the M2 group. The proteomic analysis found that M2 macrophages secreted more extracellular remodeling proteins, such as LRP1, to promote bone repair. Conclusion: In bone tissue engineering, the stiffness of repair biomaterials can affect the crosstalk between ADSCs and macrophages, thereby regulating local repair immunity and affecting bone repair.

Esophageal stricture after extensive endoscopic submucosal dissection impairs the quality of life of patients with superficial esophageal carcinoma. Beyond the limitations of conventional treatments including endoscopic balloon dilatation and the application of oral/topical corticosteroids, several cell therapies have been recently attempted. However, such methods are still limited in clinical situations and existing setups, and the efficacies are less in some cases since the transplanted cells hardly remain at the resection site for a long time due to swallowing and peristalsis of the esophagus. Thus, a cell transplantation platform directly applicable with clinically established equipment and enabling stable retention of transplanted cells can be a promising therapeutic option for better clinical outcomes. Inspired by ascidians that rapidly self-regenerate, this study demonstrates endoscopically injectable and self-crosslinkable hyaluronate that allows both endoscopic injection in a liquid state and self-crosslinking as an in situ-forming scaffold for stem cell therapy. The pre-gel solution may compatibly be applied with endoscopic tubes and needles of small diameters, based on the improved injectability compared to the previously reported endoscopically injectable hydrogel system. The hydrogel can be formed via self-crosslinking under in vivo oxidative environment, while also exhibiting superior biocompatibility. Finally, the mixture containing adipose-derived stem cells and the hydrogel can significantly alleviate esophageal stricture after endoscopic submucosal dissection (75% of circumference, 5 cm in length) in a porcine model through paracrine effects of the stem cell in the hydrogel, which modulate regenerative processes. The stricture rates on Day 21 were 79.5% ± 2.0%, 62.8% ± 1.7%, and 37.9% ± 2.9% in the control, stem cell only, and stem cell-hydrogel groups, respectively (p < 0.05). Therefore, this endoscopically injectable hydrogel-based therapeutic cell delivery system can serve as a promising platform for cell therapies in various clinically relevant situations.

Cellular senescence, a hallmark of aging, has been implicated in the pathogenesis of many major age-related disorders, including neurodegeneration, atherosclerosis, and metabolic disease. Therefore, investigating novel methods to reduce or delay the accumulation of senescent cells during aging may attenuate age-related pathologies. microRNA-449a-5p (miR-449a) is a small, noncoding RNA down-regulated with age in normal mice but maintained in long-living growth hormone (GH)-deficient Ames Dwarf (df/df) mice. We found increased fibroadipogenic precursor cells, adipose-derived stem cells, and miR-449a levels in visceral adipose tissue of long-living df/df mice. Gene target analysis and our functional study with miR-449a-5p have revealed its potential as a serotherapeutic. Here, we test the hypothesis that miR-449a reduces cellular senescence by targeting senescence-associated genes induced in response to strong mitogenic signals and other damaging stimuli. We demonstrated that GH downregulates miR-449a expression and accelerates senescence while miR-449a upregulation using mimetics reduces senescence, primarily through targeted reduction of p16Ink4a, p21Cip1, and the PI3K-mTOR signaling pathway. Our results demonstrate that miR-449a is important in modulating key signaling pathways that control cellular senescence and the progression of age-related pathologies.