Search Results (19)

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

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

Mature adipocyte-derived dedifferentiated fat (DFAT) cells show proliferative capabilities and multipotency. Given that the buccal fat pad (BFP) serves as a readily available resource for DFAT cell isolation, BFP-derived DFAT (BFP-DFAT) cells are a promising candidate in orofacial tissue engineering. In this research, we assessed the regenerative capacity of the periodontium through autologous BFP-DFAT cell transplantation in adult swine (micro-minipigs; MMPs). The BFP-DFAT cells were transplanted into inflammation-inducing two-walled infrabony periodontal defects located on the mesial of the second mandibular premolar (n = 6). Twelve weeks post-transplantation, a remarkable attachment gain was noted in the DFAT group, based on probing depths and clinical attachment levels. Histological and immunohistochemical analyses indicated new continuous cellular cementum and alveolar bone formation within the created infrabony defect. Well-organized periodontal ligament-like fibers were embedded between newly formed cementum and the alveolar bone. Histometric analysis demonstrated that the DFAT group had a 2.2-fold increase in new alveolar bone length and a 2.2-fold enhancement in vascularization than those in the control group. Except for minor inflammation in the lungs, no teratomas were detected in the recipient MMPs. BFP-DFAT cells significantly enhanced periodontal tissue regeneration, thus representing an optimal source for tissue engineering applications in dentistry. Full article

Background/Objectives: Changes in muscle mass and bone density are common in multiple myeloma (MM) patients. Dual-energy X-ray absorptiometry (DXA) offers precise, non-invasive insights into a patient’s physical condition before autologous stem cell transplantation (autoHSCT). This study examines how pre-transplant body composition impacts treatment outcomes and early complications in MM patients undergoing autoHSCT. Methods: This study is a single-center, retrospective analysis of patients with MM who were treated with first or second autoHSCT and underwent DXA pre-transplant between 11 August 2019 and 12 June 2024. Results: We conducted a study of pre-transplant body composition in 127 patients with MM. Among them, 108 (85%) qualified for first autoHSCT, while 19 (15%) qualified for a second. The median age of the patients was 64 years (range 50–73). In the Cox proportional hazards regression conducted in the group of women, Total Body %Fat was a statistically significant predictor for progression-free survival (PFS) (HR = 0.07, 95% CI = 0.01,0.6, p = 0.0157). In the Mann–Whitney U test conducted on males, Lean Mass/Height² and Appen. Lean Height² were statistically significant predictors of early infections after autoHSCT (Z = 1.98, p = 0.0473 and Z = 2.32, p = 0.0204, respectively). In males, Fat Mass/Height² was a significant predictor of non-infectious toxicity related to treatment (Z = −1.98, p = 0.0476). Conclusions: In women, higher levels of adipose tissue initially appear to exert a protective effect; however, this benefit diminishes over time, with greater fat mass eventually correlating with an increased risk of disease progression. In men, muscle mass has been identified as a significant predictor of early infection risk post-autoHSCT. Furthermore, our findings indicate that an increased amount of adipose tissue in men is statistically associated with a higher risk of non-infectious treatment-related toxicity. These conclusions highlight the critical need for further investigation into the role of body composition. Full article

Autologous fat grafting is the gold standard for treatment in patients with soft-tissue defects. However, the technique has a major limitation of unpredictable fat resorption due to insufficient blood supply in the initial phase after transplantation. To overcome this problem, we investigated the capability of a medical-grade poly L-lactide-co-poly ε-caprolactone (PLCL) scaffold to support adipose tissue and vascular regeneration. Deploying FDM 3D-printing, we produced a bioresorbable porous scaffold with interconnected pore networks to facilitate nutrient and oxygen diffusion. The compressive modulus of printed scaffold mimicked the mechanical properties of native adipose tissue. In vitro assays demonstrated that PLCL scaffolds or their degradation products supported differentiation of preadipocytes into viable mature adipocytes under appropriate induction. Interestingly, the chorioallantoic membrane assay revealed vascular invasion inside the porous scaffold, which represented a guiding structure for ingrowing blood vessels. Then, lipoaspirate-seeded scaffolds were transplanted subcutaneously into the dorsal region of immunocompetent rats (n = 16) for 1 or 2 months. The volume of adipose tissue was maintained inside the scaffold over time. Histomorphometric evaluation discovered small- and normal-sized perilipin⁺ adipocytes (no hypertrophy) classically organized into lobular structures inside the scaffold. Adipose tissue was surrounded by discrete layers of fibrous connective tissue associated with CD68⁺ macrophage patches around the scaffold filaments. Adipocyte viability, assessed via TUNEL staining, was sustained by the presence of a high number of CD31-positive vessels inside the scaffold, confirming the CAM results. Overall, our study provides proof that 3D-printed PLCL scaffolds can be used to improve fat graft volume preservation and vascularization, paving the way for new therapeutic options for soft-tissue defects. Full article

Cell-based therapy in regenerative medicine is a powerful tool that can be used both to restore various cells lost in a wide range of human disorders and in renewal processes. Stem cells show promise for universal use in clinical medicine, potentially enabling the regeneration of numerous organs and tissues in the human body. This is possible due to their self-renewal, mature cell differentiation, and factors release. To date, pluripotent stem cells seem to be the most promising. Recently, a novel stem cell niche, called multilineage-differentiating stress-enduring (Muse) cells, is emerging. These cells are of particular interest because they are pluripotent and are found in adult human mesenchymal tissues. Thanks to this, they can produce cells representative of all three germ layers. Furthermore, they can be easily harvested from fat and isolated from the mesenchymal stem cells. This makes them very promising, allowing autologous treatments and avoiding the problems of rejection typical of transplants. Muse cells have recently been employed, with encouraging results, in numerous preclinical studies performed to test their efficacy in the treatment of various pathologies. This review aimed to (1) highlight the specific potential of Muse cells and provide a better understanding of this niche and (2) originate the first organized review of already tested applications of Muse cells in regenerative medicine. The obtained results could be useful to extend the possible therapeutic applications of disease healing. Full article

Liparthroplasty has recently been discussed as a promising bridging therapy after failed conservative treatment options to postpone arthroplasty surgery of the thumb carpometacarpal joint as long as possible. The current study investigates the sustainability of this method in seven stage II and twenty-four stage III osteoarthritis patients (twenty-seven female and four male cases). Data were evaluated preinterventionally, six months postinterventionally, and two years postinterventionally, as well as a final follow-up assessment after median 5.1 years. We found a significant reduction of all postinterventional disabilities of the arm, shoulder, and hand (dash) scores and pain levels compared to the ones prior to liparthroplasty. Moreover, we even detected a reduction in both parameters within the postinterventional course, so that the DASH scores of our final investigation were significantly lower than the values after six months. Furthermore, 12 of our 31 cases demanded a surgical conversion due to recurrence of symptoms. A binary regression analysis found smokers to have 11 times higher odds for therapy failure, leading to surgical conversion. Seventeen out of nineteen patients in our final assessment stated that they were pleased with liparthroplasty. Due to favorable mid-term outcomes of 61% of the 31 initially treated patients, we recommend liparthroplasty as a reliable bridging therapy for preserving joint integrity as long as possible, especially in non-smoking patients. Full article

The resorption rate of autologous fat transfer (AFT) is 40–60% of the implanted tissue, requiring new surgical strategies for tissue reconstruction. We previously demonstrated in a rabbit model that AFT may be empowered by adipose-derived mesenchymal stromal/stem cells (AD-MSCs), which improve graft persistence by exerting proangiogenic/anti-inflammatory effects. However, their fate after implantation requires more investigation. We report a xenograft model of adipose tissue engineering in which NOD/SCID mice underwent AFT with/without human autologous AD-MSCs and were monitored for 180 days (d). The effect of AD-MSCs on AFT grafting was also monitored by evaluating the expression of CD31 and F4/80 markers. Green fluorescent protein-positive AD-MSCs (AD-MSC-GFP) were detected in fibroblastoid cells 7 days after transplantation and in mature adipocytes at 60 days, indicating both persistence and differentiation of the implanted cells. This evidence also correlated with the persistence of a higher graft weight in AFT-AD-MSC compared to AFT alone treated mice. An observation up to 180 d revealed a lower resorption rate and reduced lipidic cyst formation in the AFT-AD-MSC group, suggesting a long-term action of AD-MSCs in support of AFT performance and an anti-inflammatory/proangiogenic activity. Together, these data indicate the protective role of adipose progenitors in autologous AFT tissue resorption. Full article

Adipose tissue is composed mostly of adipocytes that are in contact with capillaries. By using a ceiling culture method based on buoyancy, lipid-free fibroblast-like cells, also known as dedifferentiated fat (DFAT) cells, can be separated from mature adipocytes with a large single lipid droplet. DFAT cells can re-establish their active proliferation ability and transdifferentiate into various cell types under appropriate culture conditions. Herein, we sought to compare the regenerative potential of collagen matrix alone (control) with autologous DFAT cell-loaded collagen matrix transplantation in adult miniature pigs (microminipigs; MMPs). We established and transplanted DFAT cells into inflammation-inducing periodontal class II furcation defects. At 12 weeks after cell transplantation, a marked attachment gain was observed based on the clinical parameters of probing depth (PD) and clinical attachment level (CAL). Additionally, micro computed tomography (CT) revealed hard tissue formation in furcation defects of the second premolar. The cemento-enamel junction and alveolar bone crest distance was significantly shorter following transplantation. Moreover, newly formed cellular cementum, well-oriented periodontal ligament-like fibers, and alveolar bone formation were observed via histological analysis. No teratomas were found in the internal organs of recipient MMPs. Taken together, these findings suggest that DFAT cells can safely enhance periodontal tissue regeneration. Full article

The skin is a natural barrier against the ultraviolet (UV) radiation of sunlight. The long-term and/or repetitive exposure to the sunlight and related UV radiation may change the skin structure, decreasing collagen production, promoting premature skin aging, which is termed “photoaging”. The signs of photoaging include wrinkle formation, mottled pigmentation, and/or cancerous changes. For many years, adipose-derived mesenchymal stem cells (AD-MSCs) and fat grafting (F-GRF) have been used to combat photoaging signs, wrinkles, loss of elasticity, and face soft tissue defects. Several studies have analyzed in vitro actions of AD-MSCs against photoaging’s effects, thanks to their migratory activity, paracrine actions, and related in vivo–ex vivo outcomes. In fact, AD-MSCs act against skin photoaging in vitro via activation of dermal fibroblast proliferation, antioxidant effect, and matrix metalloproteinases (MMPs) reduction. In vivo and ex vivo outcomes regard the local injection of AD-MSCs, F-GRF, and/or enriched-F-GRF with AD-MSCs directly in the wrinkles and the face’s soft tissue defects. This concise review summarizes the most recent in vitro, in vivo and ex vivo outcomes and developments on the effects of AD-MSCs and F-GRF against photoaging. Full article

There is a need in plastic surgery to prepare autologous adipocytes that can be transplanted in patients to reconstruct soft tissue defects caused by tumor resection, including breast cancer, and by trauma and other diseases. Direct conversion of somatic cells into adipocytes may allow sufficient functional adipocytes to be obtained for use in regeneration therapy. Chemical libraries of 10,800 molecules were screened for the ability to induce lipid accumulation in human dermal fibroblasts (HDFs) in culture. Chemical compound-mediated directly converted adipocytes (CCCAs) were characterized by lipid staining, immunostaining, and qRT-PCR, and were also tested for adipokine secretion and glucose uptake. CCCAs were also implanted into mice to examine their distribution in vivo. STK287794 was identified as a small molecule that induced the accumulation of lipid droplets in HDFs. CCCAs expressed adipocyte-related genes, secreted adiponectin and leptin, and abundantly incorporated glucose. After implantation in mice, CCCAs resided in granulation tissue and remained adipose-like. HDFs were successfully converted into adipocytes by adding a single chemical compound, STK287794. C/EBPα and PPARγ were upregulated in STK287794-treated cells, which strongly suggests involvement of these adipocyte-related transcription factors in the chemical direct conversion. Our method may be useful for the preparation of autogenous adipocytes for transplantation therapy for soft tissue defects and fat tissue atrophy. Full article

Adipose-derived mesenchymal stem cell (ASC) therapy is currently a focus of regenerative medicine. Lipoaspirate is rich in ASCs and is evolving into a promising, less-invasive tool to treat thumb carpometacarpal osteoarthritis as compared with common surgical techniques, for example, trapeziectomy or prosthesis implantation. The present study aimed to examine the effect of 1 mL intraarticular lipoaspirate injection (liparthroplasty) in 31 thumb carpometacarpal osteoarthritis patients (27 woman and four men) with a median age of 58 (interquartile range (IQR) of 10) years and Eaton–Littler Stage 2 or 3. Median pain levels assessed via visual analogue scale significantly decreased from 7 (IQR 2) to 4 (IQR 6) after six months (p < 0.0001) and 2 (IQR 5) after two years (p < 0.0001). Median pre-interventional Disabilities of the Arm, Shoulder and Hand (DASH) scores of 59 (IQR 26) significantly reduced to a value of 40 (IQR 43) after six months (p = 0.004) and to 35 (IQR 34) after two years (p < 0.0001). Subjective grip strength showed no significant improvement. However, the time until recurrence of symptoms was measured and a cumulative remission rate of 58% was detected after two years. Satisfaction rates were 68% after six months and 51% after two years. In conclusion, liparthroplasty represents a promising option to reduce pain and functional impairment and to postpone surgery for a certain period of time. Full article

The local anesthetic lidocaine, which has been used extensively during liposuction, has been reported to have cytotoxic effects and therefore would be unsuitable for use in autologous lipotransfer. We evaluated the effect of lidocaine on the distribution, number, and viability of adipose-derived stem cells (ASCs), preadipocytes, mature adipocytes, and leukocytes in the fatty and fluid portion of the lipoaspirate using antibody staining and flow cytometry analyses. Adipose tissue was harvested from 11 female patients who underwent liposuction. Abdominal subcutaneous fat tissue was infiltrated with tumescent local anesthesia, containing lidocaine on the left and lacking lidocaine on the right side of the abdomen, and harvested subsequently. Lidocaine had no influence on the relative distribution, cell number, or viability of ASCs, preadipocytes, mature adipocytes, or leukocytes in the stromal-vascular fraction. Assessing the fatty and fluid portions of the lipoaspirate, the fatty portions contained significantly more ASCs (p < 0.05), stem cells expressing the preadipocyte marker Pref-1 (p < 0.01 w/lidocaine, p < 0.05 w/o lidocaine), and mature adipocytes (p < 0.05 w/lidocaine, p < 0.01 w/o lidocaine) than the fluid portions. Only the fatty portion should be used for transplantation. This study found no evidence that would contraindicate the use of lidocaine in lipotransfer. Limitations of the study include the small sample size and the inclusion of only female patients. Full article

Due to the anatomical and functional complexity of the region, craniofacial tumor removal requires some of the most challenging surgical approaches, often complemented with advanced chemo-radiotherapy techniques. However, these modern therapies often lead to sequelae that can drastically reduce the quality of life for the surviving patients. Recent advances in the field of regenerative medicine opened new avenues for craniofacial reconstruction following head and neck cancer treatment. One of the most promising recent strategies relies on the use of autologous fat transplant. In this mini review, we briefly present some of the fat’s biological properties that make it an ideal tissue for craniofacial reconstruction following cancer treatment. We then outline the recent advances that led to a better understanding of the detailed anatomy of the craniofacial fat depots. Furthermore, we provide a succinct review of the methods used for fat harvesting, processing and engrafting in the craniofacial area after head and neck tumor removal, discussing their main applications, advantages and limitations. Full article

Autologous hematopoietic stem cell transplantation (AHCT) is an accepted strategy for various hematologic malignancies that can lead to functional impairment, fatigue, muscle wasting, and reduced quality of life (QOL). In cancer cachexia, these symptoms are associated with inflammation, hypermetabolism, and decreased anabolic hormones. The relative significance of these factors soon after AHCT setting is unclear. The purpose of this study was to characterize the acute effects of AHCT on physical function, body composition, QOL, energy expenditure, cytokines, and testosterone. Outcomes were assessed before (PRE) and 30 ± 10 days after (FU) AHCT in patients with multiple myeloma (n = 15) and non-Hodgkin lymphoma (n = 6). Six-minute walk test (6MWT; p = 0.014), lean mass (p = 0.002), and fat mass (p = 0.02) decreased; nausea and fatigue increased at FU (both p = 0.039). Recent weight change and steroid exposure were predictors of reduced aerobic capacity (p < 0.001). There were no significant changes in interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF), energy expenditure, or bioavailable testosterone. Alterations in cytokines, energy expenditure, and testosterone were not associated with functional impairment acutely following AHCT. Recent history of weight loss and steroid exposure were predictors of worse physical function after AHCT, suggesting that targeting nutritional status and myopathy may be viable strategies to mitigate these effects. Full article