Adipose-Derived Stem Cells for Facial Rejuvenation

The interest in regenerative medicine is increasing, and it is a dynamically developing branch of aesthetic surgery. Biocompatible and autologous-derived products such as platelet-rich plasma or adult mesenchymal stem cells are often used for aesthetic purposes. Their application originates from wound healing and orthopaedics. Adipose-derived stem cells are a powerful agent in skin rejuvenation. They secrete growth factors and anti-inflammatory cytokines, stimulate tissue regeneration by promoting the secretion of extracellular proteins and secrete antioxidants that neutralize free radicals. In an office procedure, without cell incubation and counting, the obtained product is stromal vascular fraction, which consists of not only stem cells but also other numerous active cells such as pericytes, preadipocytes, immune cells, and extra-cellular matrix. Adipose-derived stem cells, when injected into dermis, improved skin density and overall skin appearance, and increased skin hydration and number of capillary vessels. The main limitation of mesenchymal stem cell transfers is the survival of the graft. The final outcomes are dependent on many factors, including the age of the patient, technique of fat tissue harvesting, technique of lipoaspirate preparation, and technique of fat graft injection. It is very difficult to compare available studies because of the differences and multitude of techniques used. Fat harvesting is associated with potentially life-threatening complications, such as massive bleeding, embolism, or clots. However, most of the side effects are mild and transient: primarily hematomas, oedema, and mild pain. Mesenchymal stem cells that do not proliferate when injected into dermis promote neoangiogenesis, that is why respectful caution should be taken in the case of oncologic patients. A longer clinical observation on a higher number of participants should be performed to develop reliable indications and guidelines for transferring ADSCs.

Engineered adipose-derived stem cells with IGF-1-modified mRNA ameliorates osteoarthritis development

Background Osteoarthritis (OA), a prevalent degenerative disease characterized by degradation of extracellular matrix (ECM), still lacks effective disease-modifying therapy. Mesenchymal stem cells (MSCs) transplantation has been regarded as the most promising approach for OA treatment while engrafting cells alone might not be adequate for effective regeneration. Genetic modification has been used to optimize MSC-based therapy; however, there are still significant limitations that prevent the clinical translation of this therapy including low efficacy and safety concerns. Recently, chemically modified mRNA (modRNA) represents a promising alternative for the gene-enhanced MSC therapy. In this regard, we hypothesized that adipose derived stem cells (ADSCs) engineered with modRNA encoding insulin-like growth factor 1 (IGF-1) were superior to native ADSCs on ameliorating OA development. Methods Mouse ADSCs were acquired from adipose tissue and transfected with modRNAs. First, the kinetics and efficacy of modRNA-mediated gene transfer in mouse ADSCs were analyzed in vitro. Next, we applied an indirect co-culture system to analyze the pro-anabolic potential of IGF-1 modRNA engineered ADSCs (named as IGF-1-ADSCs) on chondrocytes. Finally, we evaluated the cell retention and chondroprotective effect of IGF-1-ADSCs in vivo using fluorescent labeling, histology and immunohistochemistry. Results modRNA transfected mouse ADSCs with high efficiency (85 ± 5%) and the IGF-1 modRNA-transfected ADSCs facilitated burst-like production of bio-functional IGF-1 protein. In vitro, IGF-1-ADSCs induced increased anabolic markers expression of chondrocytes in inflammation environment compared to untreated ADSCs. In a murine OA model, histological and immunohistochemical analysis of knee joints harvested at 4 weeks and 8 weeks after OA induction suggested IGF-1-ADSCs had superior therapeutic effect over native ADSCs demonstrated by lower histological OARSI score and decreased loss of cartilage ECM. Conclusions These findings collectively supported the therapeutic potential of IGF-1-ADSCs for clinical OA management and cartilage repair.

Intra-articular Injection of Autologous Adipose-Derived Stem Cells or Stromal Vascular Fractions: Are They Effective for Patients With Knee Osteoarthritis? A Systematic Review With Meta-analysis of Randomized Controlled Trials

Background: Intra-articular injection of adipose-derived stem cells, which are divided into adipose-derived mesenchymal stem cells (ASCs) and adipose-derived stromal vascular fractions (ADSVFs), has been reported to be a viable treatment modality for knee osteoarthritis (OA); however, its efficacy remains limited. Purpose: This study aimed to provide comprehensive information about the efficacy and safety of intra-articular injections of autologous ASCs and ADSVFs without adjuvant treatment in patients with knee OA. Study Design: Meta-analysis; Level of evidence, 1. Methods: A systematic search of the MEDLINE, Embase, Web of Science, and Cochrane Library databases was performed to identify randomized controlled trials (RCTs) that evaluated the efficacy and safety of intra-articular injections of autologous ASCs or ADSVFs without adjuvant treatments compared with placebo or hyaluronic acid in patients with knee OA. Clinically, the 100-mm visual analog scale for pain relief and the Western Ontario and McMaster Universities Osteoarthritis Index for functional improvement were implemented. Radiologically, cartilage status was assessed using magnetic resonance imaging (MRI). Procedure-related knee pain, swelling, and adverse events (AEs) were evaluated for safety. Additionally, we performed subgroup analyses comparing ASCs versus ADSVFs. Methodological quality was assessed using the modified Coleman Methodology Score (mCMS). Results: A total of 5 RCTs were included in this study. Based on the meta-analysis, ASCs or ADSVFs showed significantly better pain relief at 6 months ( Z = 7.62; P < .0001) and 12 months ( Z = 7.21; P < .0001) and functional improvement at 6 months ( Z = 4.13; P < .0001) and 12 months ( Z = 3.79; P = .0002), without a difference in procedure-related knee pain or swelling compared with controls. Although a meta-analysis with regard to cartilage improvements was not performed owing to heterogeneous MRI assessment, 3 studies reported significantly improved cartilage status after the injection. No serious AEs associated with ASCs or ADSVFs were reported. Subgroup analyses showed similar efficacy between ASC and ADSVF treatments. The median mCMS was 70 (range, 55-75). Conclusion: For patients with knee OA, intra-articular injection of autologous ASCs or ADSVFs without adjuvant treatment showed remarkable clinical efficacy and safety at short-term follow-up. Some degree of efficacy has been shown for cartilage regeneration in knee OA, although the evidence remains limited. Further RCTs that directly compare ASCs and ADSVFs are needed.

Exosomes derived from adipose-derived stem cells alleviate cigarette smoke-induced lung inflammation and injury by inhibiting alveolar macrophages pyroptosis

Background Chronic obstructive pulmonary disease (COPD) is a frequently encountered disease condition in clinical practice mainly caused by cigarette smoke (CS). The aim of this study was to investigate the protective roles of human adipose-derived stem cells-derived exosomes (ADSCs-Exo) in CS-induced lung inflammation and injury and explore the underlying mechanism by discovering the effects of ADSCs-Exo on alveolar macrophages (AMs) pyroptosis. Methods ADSCs were isolated from human adipose tissues harvested from three healthy donors, and then ADSCs-Exo were isolated. In vivo, 24 age-matched male C57BL/6 mice were exposed to CS for 4 weeks, followed by intratracheal administration of ADSCs-Exo or phosphate buffered saline. In vitro, MH-S cells, derived from mouse AMs, were stimulated by 2% CS extract (CSE) for 24 h, followed by the treatment of ADSCs-Exo or phosphate buffered saline. Pulmonary inflammation was analyzed by detecting pro-inflammatory cells and mediators in the bronchoalveolar lavage fluid. Lung histology was assessed by hematoxylin and eosin staining. Mucus production was determined by Alcian blue-periodic acid-Schiff staining. The profile of AMs pyroptosis was evaluated by detecting the levels of pyroptosis-indicated proteins. The inflammatory response in AMs and the phagocytic activity of AMs were also investigated. Results In mice exposed to CS, the levels of pro-inflammatory cells and mediators were significantly increased, mucus production was markedly increased and lung architecture was obviously disrupted. AMs pyroptosis was elevated and AMs phagocytosis was inhibited. However, the administration of ADSCs-Exo greatly reversed these alterations caused by CS exposure. Consistently, in MH-S cells with CSE-induced properties modelling those found in COPD, the cellular inflammatory response was elevated, the pyroptotic activity was upregulated while the phagocytosis was decreased. Nonetheless, these abnormalities were remarkably alleviated by the treatment of ADSCs-Exo. Conclusions ADSCs-Exo effectively attenuate CS-induced airway mucus overproduction, lung inflammation and injury by inhibiting AMs pyroptosis. Therefore, hADSCs-Exo may be a promising cell-free therapeutic candidate for CS-induced lung inflammation and injury.

Adipose Tissue Uses in Peripheral Nerve Surgery

Currently, many different techniques exist for the surgical repair of peripheral nerves. The degree of injury dictates the repair and, depending on the defect or injury of the peripheral nerve, plastic surgeons can perform nerve repairs, grafts, and transfers. All the previously listed techniques are routinely performed in human patients, but a novel addition to these peripheral nerve surgeries involves concomitant fat grafting to the repair site at the time of surgery. Fat grafting provides adipose-derived stem cells to the injury site. Though fat grafting is performed as an adjunct to some peripheral nerve surgeries, there is no clear evidence as to which procedures have improved outcomes resultant from concomitant fat grafting. This review explores the evidence presented in various animal studies regarding outcomes of fat grafting at the time of various types of peripheral nerve surgery.

The synthetic artificial stem cell (SASC): Shifting the paradigm of cell therapy in regenerative engineering

Stem cells are of great interest in tissue regeneration due to their ability to modulate the local microenvironment by secreting bioactive factors (collectively, secretome). However, secretome delivery through conditioned media still requires time-consuming cell isolation and maintenance and also may contain factors antagonistic to targeted tissue regeneration. We have therefore engineered a synthetic artificial stem cell (SASC) system which mimics the paracrine effect of the stem cell secretome and provides tailorability of the composition for targeted tissue regeneration. We report the first of many applications of the SASC system we have formulated to treat osteoarthritis (OA). Choosing growth factors important to chondrogenesis and encapsulating respective recombinant proteins in poly (lactic-coglycolic acid) 85:15 (PLGA) we fabricated the SASC system. We compared the antiinflammatory and chondroprotective effects of SASC to that of adipose-derived stem cells (ADSCs) using in vitro interleukin 1B-induced and in vivo collagenase-induced osteoarthritis rodent models. We have designed SASC as an injectable therapy with controlled release of the formulated secretome. In vitro, SASC showed significant antiinflammatory and chondroprotective effects as seen by the up-regulation of SOX9 and reduction of nitric oxide, ADAMTS5, and PRG4 genes compared to ADSCs. In vivo, treatment with SASC and ADSCs significantly attenuated cartilage degeneration and improved the biomechanical properties of the articular cartilage in comparison to OA control. This SASC system demonstrates the feasibility of developing a completely synthetic, tailorable stem cell secretome which reinforces the possibility of developing a new therapeutic strategy that provides better control over targeted tissue engineering applications.

Adipose-derived stem cells in the treatment of knee osteoarthritis: from extraction methods to the preparation of the transplant

Introduction: Recent studies have investigated the use of adipose tissue as source of mesenchymal stem cells in the treatment of knee osteoarthritis in humans. However, there are still several protocols being performed. Objective: Analyze the protocols published in the literature in the last ten years and to investigate how they are being carried out and if they are following the criteria adopted by the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Methodology: Articles from the PubMed, ScienceDirect and Lilacs database published in January / 2010 until the present time, which were evaluated in order to investigate the use of adipose-derived stem cells in the treatment of knee osteoarthritis. Results: Thirty four articles were evaluated in its entiraty. The abdominal area was the most choosen to do the liposuction, however the quantities of adipose tissue removed and the number of cells transplanted was variable. It is hightlited the enzimatic digestion of adipose tissue with collagenase as extraction method. Only 14 articles complied all the 3 criteria required to prove the real presence of mesenchymal stem cells in the samples that was transplanted. However, all the articles showed improvement of function and pain. Final considerations: Thus, even the results found are promising, the evidence is still limited in humans and the variability of the methodology makes it difficult to standardize the technique, also its implementation as a reference in the treatment of knee osteoarthritis.

Porous Cellulose-Collagen Scaffolds For Soft Tissue Regeneration: Influence of Cellulose Derivatives On Mechanical Properties And Compatibility With Adipose-Derived Stem Cells.

This study deals with cellulose derivatives in relation to the collagen fibrils in composite collagen-cellulose scaffolds for soft tissue engineering. Two types of cellulose, i.e., oxidized cellulose (OC) and carboxymethyl cellulose (CMC), were blended with collagen (Col) to enhance its elasticity, stability and sorptive biological properties, e.g. hemostatic and antibacterial features. The addition of OC supported the resistivity of the Col fibrils in a dry environment, while in a moist environment OC caused a radical drop. The addition of CMC reduced the mechanical strength of the Col fibrils in both environments. The elongation of the Col fibrils was increased by both types of cellulose derivatives in both environments, which is closely related to tissue like behaviour. In these various mechanical environments, the ability of human adipose-derived stem cells (hADSCs) to adhere and proliferate was significantly greater in the Col and Col/OC scaffolds than in the Col/CMC scaffold. This is explained by deficient mechanical support and loss of stiffness due to the high swelling capacity of CMC. Although Col/OC and Col/CMC acted differently in terms of mechanical properties, both materials were observed to be cytocompatible, with varying degrees of further support for cell adhesion and proliferation. While Col/OC can serve as a scaffolding material for vascular tissue engineering and for skin tissue engineering, Col/CMC seems to be more suitable for moist wound healing, e.g. as a mucoadhesive gel for exudate removal, since there was almost no cell adhesion.