Search Results (166)

Background: Autologous fat grafting is increasingly used in daily clinical practice across various surgical fields, including the treatment of chronic wounds, scars, burns, and non-healing perianal fistulas. Recently, some studies have shown that non-enteric cutaneous fistulas can also benefit from adipose tissue injections, but the efficacy remains unclear. This study aims to systematically review the literature on fat grafting in the context of non-enteric cutaneous fistulas and to assess treatment outcomes. Methods: A comprehensive search of the PubMed/Medline database was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines up to January 2024 without restrictions on the time period or the language of publication. Results: Seven studies meeting the inclusion criteria were analyzed, encompassing 13 patients with non-healing cutaneous fistulas treated with injections of autologous fat. The mean age of the patients was 58 ± 3 years, of which 85% had comorbidities. Fat grafting resulted in complete healing in 92% of the cases, with a mean fistula persistence of 158 days before treatment. Treatment protocols varied among patients, including preparation of the fistulous tract, fat processing techniques, and suturing of the fistulous orifice. Conclusions: The results highlight the potential of autologous fat grafting in promoting tissue regeneration and healing of non-enteric cutaneous fistulas. Standardized protocols are essential to confirm and optimize treatment efficacy and, eventually, improve patient outcomes. Further research with a larger sample size and standardization is needed to confirm fat graft efficacy. Full article

Background: Chronic wounds represent a persistent clinical challenge and impose a considerable burden on healthcare systems. These lesions often require multidisciplinary management due to underlying factors such as microbial colonization, impaired immunity, and vascular insufficiencies. Regenerative therapies, particularly autologous approaches, have emerged as promising strategies to enhance wound healing. Adipose tissue-derived stem cells (ADSCs) and platelet-rich plasma (PRP) may improve outcomes through paracrine effects and growth factor release. Methods: A prospective observational study was conducted on 31 patients with chronic wounds that were unresponsive to conservative treatment for over six weeks. Clinical and photographic evaluations were employed to monitor healing. All patients underwent surgical debridement, with adjunctive interventions—negative pressure wound therapy, grafting, or flaps—applied as needed. PRP infiltration and/or autologous adipose tissue transfer were administered based on wound characteristics. Wound area reduction was the primary outcome measure. Results: The cohort included 17 males and 14 females (mean age: 59 years). Etiologies included venous insufficiency (39%), diabetes mellitus (25%), arterial insufficiency (16%), and trauma (16%). Most lesions (84%) were located on the lower limbs. All patients received PRP therapy; five underwent combined PRP and fat grafting. Over the study period, 64% of the patients exhibited >80% wound area reduction, with complete healing in 48.3% and a mean healing time of 49 days. Conclusions: PRP therapy proved to be a safe, effective, and adaptable treatment, promoting substantial healing in chronic wounds. Autologous adipose tissue transfer did not confer additional benefit. PRP may warrant inclusion in national treatment protocols. Full article

Micro-fragmented adipose tissue (MFAT) is a promising autologous therapy for knee osteoarthritis. To avoid repeated liposuction procedures for its clinical application, MFAT obtained from patients with knee osteoarthritis was stored at −80 °C in a tissue bank. This study describes the preparation, cryopreservation, thawing, and washing, as well as comprehensive analysis of cell populations in fresh and MFAT thawed after two years. Immunophenotyping of both fresh and thawed MFAT showed a significant presence of endothelial progenitors and pericytes in the stromal vascular fraction. Viability before (59.75%) and after freezing (55.73%) showed no significant difference. However, the average cell count per gram of MFAT was significantly reduced in thawed samples (3.00 × 10⁵) compared to fresh ones (5.64 × 10⁵), likely due to processing steps. Thawed MFAT samples showed increased CD73 expression on the CD31^highCD34^high subset of EP and SA-ASC, as well as increased expression of CD105 on EP, the CD31^lowCD34^low subset of EP, pericytes, and SA-ASC. Microbiological testing confirmed 100% sterility, and double washing efficiently removed DMSO, confirming sample safety. Histological analysis revealed healthy, uniformly shaped adipocytes with intact membranes. This approach allows accurate estimation of cell yield for intra-articular injection, ensuring delivery of the target cell number into the knee. Quality control analysis confirms that cryopreserved MFAT retains high cellular and structural integrity, supporting its safety and suitability for clinical application. Full article

Current treatment strategies for partial tendon tears often lack the capacity to promote true tissue regeneration and improve long-term clinical outcomes. This study tested the hypothesis that treatment of a partial defect in the rabbit common calcaneus tendon (CCT) with uncultured, unmodified, autologous, adipose-derived regenerative cells (UA-ADRCs) enables regenerative healing without scar formation. A full-thickness, 3 mm defect was produced in the midsubstance of the right gastrocnemius tendon, a component of the CCT, in adult female New Zealand white rabbits. Animals received either an injection of 28.3 × 10⁶ UA-ADRCs in 0.5 mL Ringer’s lactated solution (RLS) or saline, or RLS or saline alone as sham treatment. Tendons were analyzed 4 or 12 weeks post-treatment using histology, immunohistochemistry and non-destructive biomechanical testing. UA-ADRC-treated tendons showed newly formed connective tissue consistent with tendon regeneration, whereas sham-treated tendons developed scar tissue. Biomechanical testing showed significantly higher percent relaxation in UA-ADRC-treated tendons compared to sham controls (p < 0.05), indicating greater viscoelasticity characteristic of healthy or well-integrated tissue. Together, these findings suggest that UA-ADRC therapy may provide a regenerative, structure-modifying treatment for partial tendon tears. Full article

Mesenchymal stem cells (MSCs) exhibit low immunogenicity, multipotency, and are abundantly present in adipose tissue, making this tissue an easily accessible resource for regenerative medicine. Different commercial procedures have been developed to micro-fragment the adipose tissue aspirate from patients before its reinjection. We explored a commercial device which mechanically micro-fragments human lipoaspirate (LA) resulting in a homogeneous micro-fragmentation of fat tissue (MFAT). This device has been successfully employed in several clinical applications involving autologous adipose tissue transplantation. Here, we compare the untargeted/targeted lipidomic profile of LA and MFAT looking for differences in terms of qualitative modifications occurring during the handling of the original LA material. In MFAT, different lipid subclasses such as diacylglycerols, triacylglycerols, phospholipids, and sphingolipids are more represented than in LA. In addition, via targeted fatty acids analysis, we found a lower abundance of monounsaturated fatty acids in MFAT. The biological implications of these findings must be better investigated to contribute to a better understanding of the clinical efficacy of MFAT and for its potential use as a scaffold for drug delivery applications. Full article

Background: The traditional management of acute burn wounds using eschar debridement followed by split-thickness skin grafting has notable drawbacks. Stromal vascular fraction (SVF), derived from autologous adipose tissue, promotes epithelialization and angiogenesis, while platelet-rich fibrin (PRF), obtained via centrifugation of patient blood, enhances wound healing. This study retrospectively analyzes the outcomes of patients with thermal injuries treated with a combination of topical SVF and PRF at the University Hospital Zurich Burn Center. Methods: From 2018 to 2020, 13 patients with deep partial-thickness burns (DPTBs) or mixed-pattern burns (MPBs) received combined topical SVF and PRF treatment. Eschar removal was performed enzymatically or surgically following hydrotherapy. SVF was collected via liposuction, and PRF from centrifuged blood. Healing progress, additional surgeries, and scar outcomes (assessed by the Manchester Scar Scale, MSS) were evaluated retrospectively. Results: The mean total body surface area burned was 29.6%, with 6.3% treated using SVF and PRF. Five patients required further surgical intervention for residual defects. Complete healing occurred within 20 days in patients without residual defects and within 51 days in those with defects. Higher MSS scores were observed in patients requiring additional surgery. No adverse effects were noted. Conclusions: Topical SVF and PRF offer a potentially less-invasive treatment for MPB and DPTB. However, due to frequent residual defects and regulatory concerns around SVF use, this approach cannot yet be considered a standard treatment. Full article

The impact of donor age on Adipose-derived mesenchymal stem cell (ASC) functionality and safety remains insufficiently characterized, particularly in equine models. This study investigates the influence of age on ASCs proliferation dynamics and the expression of tumorigenic and apoptosis-related markers. Equine ASCs were isolated from juvenile (<5 years), middle-aged (5–15 years), and geriatric (>15 years) horses and assayed across multiple passages. The relative mRNA expressions of pluripotency (Oct4), tumorigenic (CA9), and apoptosis-related (Bax and Bcl 2) markers were evaluated. The Gompertz growth model, population doubling time (PDT), and tissue non-specific ALP activity also followed. The expression of pluripotency and tumorigenic markers showed passage-dependent up-regulation, raising concerns about prolonged culture expansion. Apoptotic regulation displayed a shift with aging, as evidenced by alterations in the Bax/Bcl2 ratio, suggesting compromised cell survival in older ASCs. An age-associated decline in proliferation rates was established, as evidenced by declining alkaline phosphatase (ALP) activity. These findings underscore the necessity for stringent age-based selection criteria in equine stem cell therapies and the challenges associated with using autologous stem cells for regenerative therapies in aged horses. Future research should focus on molecular interventions to mitigate age-related functional decline, ensuring the safety and efficacy of ASCs-based regenerative medicine in equine practice. Full article

Soft tissue reconstruction remains a challenge in clinical practice, particularly for restoring substantial volume loss due to surgical resections or contour deformities. Current methods, such as autologous fat transplantation, have limitations, including donor site morbidity and insufficient tissue availability, necessitating an innovative approach. This study characterizes alloClae, a minimally manipulated human-derived adipose allograft prepared using a detergent-based protocol to reduce DNA content while preserving adipose tissue structure. Proteomic analysis revealed that alloClae retains key native proteins critical for graft integration with the host and stability, with key extracellular matrix (ECM) components, collagens, elastins, and laminin, which are more concentrated as a result of the detergent-based protocol. Biocompatibility of alloClae was assessed in vitro using cytotoxicity and cell viability assays in fibroblast cultures, revealing no adverse effects on cell viability, membrane integrity, or oxidative stress. Additionally, in vitro studies with adipose-derived stem cells (ASCs) demonstrated attachment and differentiation, with lipid droplet accumulation observed by day 14, indicating support for adipogenesis. A 6-month longitudinal study in athymic mice showed stable graft retention, host cell infiltration, and formation of new adipocytes and vasculature within alloClae by 3 months. The findings highlight alloClae’s ability to support host-driven adipogenesis and angiogenesis while maintaining graft stability throughout the study period. It presents a promising alternative to the existing graft materials, offering a clinically translatable solution for soft tissue reconstruction. Full article

Background: An autologous minimally manipulated homologous adipose tissue (AMHAT) fabricated using three-dimensional (3D) bioprinting has shown potential in the treatment of diabetic foot ulcers and other chronic wounds. Methods: This study assessed the efficacy of AMHAT fabricated using 3D bioprinting for treating skin defects after a wide excision of skin cancer lesions where primary closure was not feasible. A total of 10 consecutive patients were included. The wounds were photographed and analyzed using AI, and the fat tissue harvested from the lower abdomen was processed into an AMHAT patch using a 3D bioprinter. The wound area was measured weekly until complete wound closure was achieved. Results: The area of the skin defects ranged from 1.77–6.22 cm², averaging 2.72 cm². Complete closure was achieved in 3–5 (average, 4.2) weeks. The residual area decreased from 52% after 1 week to 3% after 4 weeks. The scar appearance was esthetically favorable, with one patient showing mild nostril asymmetry. Furthermore, patient-reported outcome evaluation using the Japanese version of SCAR-Q for postoperative scars showed a very high level of satisfaction. Conclusions: The 3D bioprinted AMHAT accelerates wound healing with minimal scarring, offering an important option for skin defects where esthetics are a priority. Full article

The use of autologous biological preparations (ABPs) and their combinations fills the void in healthcare treatment options that exists between surgical procedures, like plastic reconstructive, cosmetic, and orthopedic surgeries; non-surgical musculoskeletal biological procedures; and current pharmaceutical treatments. ABPs, including high-density platelet-rich plasma (HD-PRP), bone marrow aspirate concentrates (BMACs), and adipose tissue preparations, with their unique stromal vascular fractions (SVFs), can play important roles in tissue regeneration and repair processes. They can be easily and safely prepared at the point of care. Healthcare professionals can employ ABPs to mimic the classical wound healing cascade, initiate the angiogenesis cascade, and induce tissue regenerative pathways, aiming to restore the integrity and function of damaged tissues. In this review, we will address combining autologous HD-PRP with adipose tissue, in particular the tissue stromal vascular fraction (t-SVF), as we believe that this biocellular combination demonstrates a synergistic effect, where the HD-PRP constituents enhance the regenerative potential of t-SVF and its adipose-derived mesenchymal stem cells (AD-MSCs) and pericytes, leading to improved functional tissue repair, tissue regeneration, and wound healing in variety of clinical applications. We will address some relevant platelet bio-physiological aspects, since these properties contribute to the synergistic effects of combining HD-PRP with t-SVF, promoting overall better outcomes in chronic inflammatory conditions, soft tissue repair, and tissue rejuvenation. Full article

Knee osteoarthritis (OA) is a chronic, progressive, inflammatory, and degenerative whole-joint disease. Early-stage OA treatments typically include physiotherapy, weight-loss, pain relief medications, and intra-articular knee injections, such as corticosteroids, hyaluronic acid, or platelet-rich plasma. These treatments primarily provide symptomatic relief rather than reversing or halting disease progression. Recently, mesenchymal stromal cell (MSC) injections have garnered attention due to their immunomodulatory and regenerative capacities. MSCs, which can be derived from sources such as bone marrow, umbilical cord, or adipose tissue, and can be allogeneic or autologous, have demonstrated promising results in both animal models and several human studies. However, different protocols have been employed, presenting challenges for comparing outcomes. In this review, we address these variable settings, evaluate current practices, and identify key factors critical in optimizing MSC-based therapies by critically reviewing clinical trials of ex vivo expanded MSC therapies for OA undertaken between 2008 and 2023. Specific attention was given to two key aspects: (1) the cell culture process employed in manufacturing of autologous or allogeneic MSC products, and (2) the post-culture methods employed in storage, reconstitution and administration of the MSCs. Our findings suggest that standardizing MSC production for clinical applications remains a significant challenge, primarily due to variations in tissue sources, harvesting techniques, and manufacturing protocols, and due to broad discrepancies in reporting. Thus, we propose a set of minimal reporting criteria to guide future clinical trials. A common reporting guideline is a critical step towards a more standardized MSC production across different laboratories and clinical settings, thereby enhancing reproducibility and advancing the field of regenerative medicine for knee OA, as well as other disease settings. Full article

Background/Objectives: Treatment of knee osteoarthritis (OA) with autologous stem cells from microfragmented adipose tissue (MFAT) has shown promising but varying results. Multiple stem cell types, including CD34⁺, CD146⁺, and CD271⁺ stem cells, have been identified within MFAT. Patient-specific heterogeneity in stem cell populations and the content of highly potent cells may be determining factors for a successful treatment outcome. The current study aimed to identify the most promising stem cell type in MFAT to treat OA, focusing on their chondrogenic and osteogenic differentiation performance. Methods: CD34⁺, CD146⁺, and CD271⁺ stem cells from the MFAT of eight patients with knee OA were separated using magnetic-activated cell sorting (MACS) and analyzed as subtypes. Unsorted cells were used as a control. Chondrogenic and osteogenic in vitro differentiation were assessed through Safranin-O and H&E staining, pellet size, and qPCR for chondrogenesis, as well as Alizarin Red S staining and qPCR for osteogenesis. Results: CD34⁺, CD146⁺, and CD271⁺ stem cells were doubled using MACS. All subtypes were able to undergo osteogenic differentiation with Alizarin Red S staining, revealing a significant increase in calcium deposits of induced cells compared to non-induced controls. CD146⁺ stem cells showed higher calcium deposition compared to CD34⁺, CD271⁺, and unsorted stem cells. All cell types could form chondrogenic pellets. CD271⁺ stem cells produced more proteoglycans, as shown by Safranin-O staining, than CD34⁺ and CD146⁺ stem cells, but not more than the unsorted stem cells. After differentiation induction, all cell types showed an upregulation of most chondrogenic and osteogenic biomarkers. Conclusions: CD146⁺ stem cells showed the highest osteogenic differentiation performance for calcium deposition, while CD271⁺ stem cells showed the greatest chondrogenic differentiation performance for proteoglycan formation. The prevalence of these stem cell types may play a critical role in the clinical effectiveness when treating OA. Full article

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. Full article

The skin functions as the body’s primary defense barrier; when compromised, it can lead to dehydration, infection, shock, or potentially life-threatening conditions. Miniature pigs exhibit skin characteristics and healing processes highly analogous to humans. Mesenchymal stem cells contribute to skin injury repair through a paracrine mechanism involving exosomes. This research examines whether adipose-derived MSC exosomes effectively enhance healing following autologous skin grafting in miniature pigs. It also compares the roles and distinctions of ADSCs and ADSC-Exos in inflammatory responses and tissue regeneration. This study found significantly reduced levels of oxidative stress products and pro-inflammatory factors, while antioxidant factors, anti-inflammatory factors, and pro-regenerative factors were elevated, and anti-regenerative factor levels decreased. Moreover, the expression levels of key markers—namely, PI3K, Akt, and mTOR—in the regeneration-associated signaling pathway were increased. The alterations in these indicators indicate that ADSC-Exos can regulate inflammatory responses and promote regeneration. This study provides a novel theoretical foundation for the implementation of acellular therapy in clinical settings. Full article

Bilio-biliary anastomosis (BBA) is a critical surgical procedure that is performed with the objective of restoring bile duct continuity. This procedure is often required in cases where there has been an injury to the extrahepatic bile ducts or during liver transplantation. Despite advances in surgical techniques, the healing of BBA remains a significant challenge, with complications such as stricture formation and leakage affecting patient outcomes. The stromal vascular fraction (SVF), a heterogeneous cell population derived from adipose tissue, has demonstrated promise in regenerative medicine due to its rich content of stem cells, endothelial progenitor cells, and growth factors. The objective of this study was to evaluate the potential of locally administered autologous SVF to enhance the healing of BBAs. Bilio-biliary anastomosis was performed on a swine model (female Landrace pigs). Six swine were divided into two groups: the treatment group (n = 3) received a local application of autologous SVF around the anastomosis site immediately following BBA formation, while the control group (n = 3) received saline. The primary outcomes were assessed over an eight-week period post-surgery, and included anastomosis healing, stricture formation, and bile leakage. Histological analysis was performed to evaluate fibrosis, angiogenesis, and inflammation. Immunohistochemistry was conducted to assess healing-related markers (CD34, α-SMA) and the immunological microenvironment (CD3, CD10, tryptase). The SVF-treated group exhibited significantly enhanced healing of the BBA. Histological examination revealed increased angiogenesis and reduced fibrosis in the SVF group. Immunohistochemical staining demonstrated higher vascular density in the anastomosed area of the SVF-treated group (390 vs. 210 vessels per 1 mm², p = 0.0027), as well as a decrease in wall thickness (1.9 vs. 1.0 mm, p = 0.0014). There were no statistically significant differences in mast cell presence (p = 0.40). Immunohistochemical staining confirmed the overexpression of markers associated with tissue repair. Local injections of autologous SVF at the site of BBA have been demonstrated to significantly enhance healing and promote tissue regeneration. These findings suggest that SVF could be a valuable adjunctive therapy in BBA surgery, potentially improving surgical outcomes. However, further investigation is needed to explore the clinical applicability and long-term benefits of this novel approach in clinical practice as a minimally manipulated cell application. Full article