Polyketides with α-glucosidase inhibitory and neuroprotective activities from Aspergillus versicolor associated with Pedicularis sylvatica.

Aspergillus versicolor, an endophytic fungus associated with the herbal medicine Pedicularis sylvatica, produced four new polyketides, aspeversins A-D (1-2 and 5-6) and four known compounds, O-methylaverufin (2), aversin (3), varilactone A (7) and spirosorbicillinol A (8). Their structures were elucidated by extensive spectroscopic data analysis, and their absolute configurations were determined by calculated electronic circular dichroism (ECD) and Mo2(AcO)4-induced CD data. Compound 5 was found to exhibit α-glucosidase inhibitory activity with an IC50 value of 25.57 µM. An enzyme kinetic study indicated that 5 was a typical uncompetitive inhibitor toward α-glucosidase, which was supported by a molecular docking study. Moreover, compounds 1-3 and 5 also improved the cell viability of PC12 cells on a 1-methyl-4-phenylpyridinium (MPP+)-induced Parkinson's disease model, indicating their neuroprotective potential as antiparkinsonian agents.

Establishment of Early Blood Perfusion Promotes CXCL12 Expression and Recruits Monocytes/Macrophages in Damaged Adipose Tissue in Mice Model.

BACKGROUND: Blood perfusion in the recipient site is important for adipose tissue repair after fat grafting. It delivers host-derived macrophages derived from monocytes in bone marrow to initiate inflammatory reactions and regenerative responses. According to the ability of CXCL12, a stromal cell-derived factor, to recruit monocytes/macrophages, we studied its effect on adipose tissue repair and regeneration under ischemic and normal conditions. METHODS: Each inguinal fat pad was crushed for 30 seconds with a clamp in mice (n = 35). The left inguinal vessels were divided and cut off (ischemic group), while the right inguinal vessels were kept patent (control group). Seven animals were sacrificed at 1, 3, 7, 14, and 30 days after surgery, and macrophages (Mac2 and CD206) and adipocytes (perilipin) were assessed. Levels of inflammatory factors (interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α) and CXCL12 were measured by quantitative PCR. RESULTS: The number of macrophages was higher in the control group than in the ischemic group at day 3 (10.33 ± 2.40 vs. 1.33 ± 0.33, p = 0.021). The percentage of M2 macrophages was higher in the control group than in the ischemic group at day 7 (p<0.05). The levels of inflammatory factors and CXCL12 were higher in the control group than in the ischemic group at the early stage (p = 0.038). CONCLUSIONS: Established blood perfusion leads to up-regulation of CXCL12 during adipose tissue repair and regeneration, which may increase recruitment of monocytes to damaged adipose tissue. These findings increase understanding of the cellular events involved in fat graft survival after grafting. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

[Progress in application of adult endogenous neurogenesis in brain injury repair].

Persistent neurogenesis exists in the subventricular zone (SVZ) of the ventricles and the subgranular zone (SGZ) of the dentate gyrus of the hippocampus in the adult mammalian brain. Adult endogenous neurogenesis not only plays an important role in the normal brain function, but also has important significance in the repair and treatment of brain injury or brain diseases. This article reviews the process of adult endogenous neurogenesis and its application in the repair of traumatic brain injury (TBI) or ischemic stroke, and discusses the strategies of activating adult endogenous neurogenesis to repair brain injury and its practical significance in promoting functional recovery after brain injury.

Alternatively activated macrophages at the recipient site improve fat graft retention by promoting angiogenesis and adipogenesis.

The inflammatory response mediated by macrophages plays a role in tissue repair. Macrophages preferentially infiltrate the donor site and subsequently, infiltrate the recipient site after fat grafting. This study aimed to trace host-derived macrophages and to evaluate the effects of macrophage infiltration at the recipient site during the early stage on long-term fat graft retention. In our novel mouse model, all mice underwent simulated liposuction and were divided into 2 groups. The fat procurement plus grafting (Pro-Grafting) group was engrafted with prepared fat (0.3 ml). The pro-Grafting+M2 group was engrafted with prepared fat (0.3 ml) mixed with 1.0 × 106 GFP+M0 macrophages, and then, 2 ng IL-4 was injected into the grafts on Day 3. In addition, 1.0 × 106 GFP+M0 macrophages were injected into the tail vein for tracing in the Pro-Grafting group. As a result, GFP+macrophages first infiltrated the donor site and subsequently infiltrated the recipient site in the Pro-Grafting group. The long-term retention rate was higher in the Pro-Grafting+M2 group (52% ± 6.5%) than in the Pro-Grafting group (40% ± 3.5%). CD34+ and CD31+ areas were observed earlier, and expression of the adipogenic proteins PPAR-γ, C/EBP and AP2 was higher in the Pro-Grafting+M2 group than in the Pro-Grafting group. The host macrophages preferentially infiltrate the donor site, and then, infiltrate the recipient site after fat grafting. At the early stage, an increase in macrophages at the recipient site may promote vascularization and regeneration, and thereby improve the fat graft retention rate.

[Research progress on muscle spindle morphology].

Muscle spindle is the key proprioceptor in skeletal muscles and plays important roles in many physiological activities, such as maintaining posture, regulating movement and controlling speed variation. It has significant clinical relevance and is emerging as a promising therapeutic target for the treatment of motor functional impairment and metabolic diseases. In this review, we summarized muscle spindle distribution and the mechanism of mechanical signal transmission, and reviewed the research progress on morphological and structural characteristics of muscle spindles.

The effects of macrophage-mediated inflammatory response to the donor site on long-term retention of a fat graft in the recipient site in a mice model.

Inflammatory responses mediated by macrophages play a role in tissue repair. However, it is unclear whether the repair in the donor site after liposuction would have any effects on fat graft retention in the recipient site. This study is designed to evaluate the effects of a macrophage-mediated inflammatory response in donor sites on long-term retention of fat grafting. In this study, mice were randomly divided into two groups. One underwent simulated liposuction, called the fat procurement plus grafting (Pro-Grafting) group, and the other underwent sham surgery, called the fat grafting only (Grafting Only) group. The prepared fat (0.3 ml each) was engrafted and cellular events over a 90-day period were assessed. We found macrophages were infiltrated into adipose tissue at the recipient site in the Grafting Only group within 7 days and the repair essentially completed within 30 days. By contrast, few macrophages infiltrated the recipient site in the Pro-Grafting group within 7 days and the entire remodeling process took 30 days longer in the Pro-Grafting than the Grafting Only group. Moreover, C-reactive protein levels were immediately upregulated after surgery, and the inflammatory factors' expression was higher at the donor rather than the recipient site. However, the repair processes and the long-term retention rate became normal when the adipose tissue was grafted after the donor site did not require macrophages for repair. Therefore, we suggest higher inflammatory factors promote macrophage infiltration and the adipose tissue regeneration process at the donor site. This process is delayed at the recipient site, which may affect long-term retention of fat grafts.

Botulinum Toxin A Improves Supramuscular Fat Graft Retention by Enhancing Angiogenesis and Adipogenesis.

BACKGROUND: Autologous fat grafting is commonly used for soft-tissue augmentation and reconstruction in plastic surgery. However, long-term graft retention rates are unpredictable, especially in muscle-related fat grafting. OBJECTIVE: To determine whether botulinum neurotoxin type A (BoNTA) may improve supramuscular fat grafting retention by reducing muscle movement, thereby enhancing angiogenesis and adipogenesis. MATERIALS AND METHODS: Pre-BTX+ nude mice were injected with BoNTA on the right quadriceps femoris and underwent supramuscular fat grafting 1 week later. BTX+ nude mice simultaneously underwent BoNTA injection and transplantation. Control nude mice underwent transplantation without BoNTA. Graft volumes were determined, and grafts underwent histological analyses and immunostaining. CatWalk XT gait analysis was conducted on BTX+ mice. RESULTS: Pre-BTX+ and BTX+ groups had significantly higher retention rates and exhibited better angiogenesis and adipocyte survival than the Control group. CONCLUSION: BoNTA injections improved the long-term retention of supramuscular fat grafts by reducing muscle movement, possibly by augmenting angiogenesis and adipogenesis.

Non-human primate models of focal cortical ischemia for neuronal replacement therapy.

Despite the high prevalence, stroke remains incurable due to the limited regeneration capacity in the central nervous system. Neuronal replacement strategies are highly diverse biomedical fields that attempt to replace lost neurons by utilizing exogenous stem cell transplants, biomaterials, and direct neuronal reprogramming. Although these approaches have achieved encouraging outcomes mostly in the rodent stroke model, further preclinical validation in non-human primates (NHP) is still needed prior to clinical trials. In this paper, we briefly review the recent progress of promising neuronal replacement therapy in NHP stroke studies. Moreover, we summarize the key characteristics of the NHP as highly valuable translational tools and discuss (1) NHP species and their advantages in terms of genetics, physiology, neuroanatomy, immunology, and behavior; (2) various methods for establishing NHP focal ischemic models to study the regenerative and plastic changes associated with motor functional recovery; and (3) a comprehensive analysis of experimentally and clinically accessible outcomes and a potential adaptive mechanism. Our review specifically aims to facilitate the selection of the appropriate NHP cortical ischemic models and efficient prognostic evaluation methods in preclinical stroke research design of neuronal replacement strategies.

Early Angiogenesis-Dependent CXCL12 Attracts Adipose-Derived Stem Cells to Promote the Repair of Fat Grafting in a Mouse Model.

BACKGROUND: The unpredictable and unstable tissue retention rate of autologous fat grafting remains an obstacle faced by plastic surgeons. The authors' previous study using a fat grafting mouse model with donor sites showed that adipose-derived stem cell (ASC) infiltration in the recipient site was delayed, leading to poor regeneration and lower retention. Thus, the mechanism behind the differential infiltration of ASCs needed to be explored. METHODS: First, the authors locally injected C-X-C chemokine ligand 12 (CXCL12) or C-X-C motif chemokine receptor 4 (CXCR4) inhibitor AMD3100 in the recipient or donor site, respectively (CXCL12 + AMD3100 - , CXCL12 - AMD3100 + , and CXCL12 + AMD3100 + groups). The authors compared the migration of ASCs, adipose regeneration, and long-term retention. Next, the authors explored the role of angiogenesis using a normal/ischemic mice model in which the authors test the expression of CXCL12/CXCR4, migration of ASCs, and adipose regeneration. RESULTS: Blocking CXCL12 in the donor site using AMD3100 (CXCL12 - AMD3100 + and CXCL12+AMD3100+ groups) could accelerate ASC infiltration and promote adipose regeneration and long-term retention ( P < 0.05) compared with the other groups. CXCL12 and its receptor CXCR4 were more highly expressed in normal than in ischemic adipose tissue; consistently, there were more ASCs infiltrating normal than ischemic adipose tissue early after surgery ( P < 0.05). CONCLUSION: Early angiogenesis is essential for CXCL12 in promoting ASC infiltration, improving adipose tissue repair in the recipient site, and potentiating the long-term fat retention rate. CLINICAL RELEVANCE STATEMENT: The authors provide a proof-of-concept way to improve the outcomes of fat grafting by locally injecting AMD3100, also known as plerixafor, to the donor site.

Circuit reconstruction of newborn neurons after spinal cord injury in adult rats via an NT3-chitosan scaffold.

An implanted neurotrophin-3 (NT3)-chitosan scaffold can recruit endogenous neural stem cells to migrate to a lesion region and differentiate into mature neurons after adult spinal cord injury (SCI). However, the identities of these newborn neurons and whether they can form functional synapses and circuits to promote recovery after paraplegia remain unknown. By using combined advanced technologies, we revealed here that the newborn neurons of several subtypes received synaptic input from the corticospinal tract (CST), rubrospinal tract (RST), and supraspinal tracts. They formed a functional neural circuit at the injured spinal region, further driving the local circuits beneath the lesion. Our results showed that the NT3-chitosan scaffold facilitated the maturation of spinal neurons and the reestablishment of the spinal neural circuit in the lesion region 12 weeks after SCI. Transsynaptic virus experiments revealed that these newborn spinal neurons received synaptic connections from the CST and RST and drove the neural circuit beneath the lesion via newly formed synapses. These re-established circuits successfully recovered the formation and function of the neuromuscular junction (NMJ) beneath the lesion spinal segments. These findings suggest that the NT3-chitosan scaffold promotes the formation of relay neural circuits to accommodate various types of brain descending inputs and facilitate functional recovery after paraplegia.

Proper wiring of newborn neurons to control bladder function after complete spinal cord injury.

Activation of endogenous neurogenesis by bioactive materials enables restoration of sensory/motor function after complete spinal cord injury (SCI) via formation of new relay neural circuits. The underlying wiring logic of newborn neurons in adult central nervous system (CNS) is unknown. Here, we report neurotrophin3-loaded chitosan biomaterial substantially recovered bladder function after SCI. Multiple neuro-circuitry tracing technologies using pseudorabies virus (PRV), rabies virus (RV), and anterograde adeno-associated virus (AAV), demonstrated that newborn neurons were integrated into the micturition neural circuits and reconnected higher brain centers and lower spinal cord centers to control voiding, and participated in the restoration of the lower urinary tract function, even in the absence of long-distance axonal regeneration. Opto- and chemo-genetic studies further supported the notion that the supraspinal control of the lower urinary tract function was partially recovered. Our data demonstrated that regenerated relay neurons could be properly integrated into disrupted long-range neural circuits to restore function of adult CNS.

Adipose-derived stem cells regulate CD4+ T-cell-mediated macrophage polarization and fibrosis in fat grafting in a mouse model.

Autologous fat grafting is becoming increasingly common worldly. However, the long-term retention of fat grafting is still unpredictable due to the inevitable fibrosis arising during tissue repair. Fibrosis may be regulated by T-cell immune responses that are influenced by adipose-derived stem cells (ASCs). Therefore, we hypothesized that overly abundant ASCs might promote fibrosis by promoting T-cell immune responses to adipose tissue. We performed 0.3 ml fat grafts with 104/ml, 106/ml and 108/ml ASCs and control group in C57 BL/6 mice in vivo. We observed retention, fibrosis, T-cell immunity, and macrophage infiltration over 12 weeks. Besides, CD4+ T-helper 1 (Th1) cells and T-helper 2 (Th2) cells were co-cultured with ASCs or ASCs conditioned media (ASCs-CM) in vitro. We detected the ratio of Th2%/Th1%. Results showed that the retention rate was higher in 104 group, while even lower in 108 group with significantly increased inflammation and fibrosis than control group at week 12 in vivo. There was no significance between control group and 106 group. Also, 108 group increased the infiltration of M2 macrophages, CD4+ T-cells and Th2/Th1 ratio. In vitro, the ratio of Th2%/Th1% induced by ASCs-transwell group was higher than ASCs-CM group and showed concentration-dependent. Accordingly, high concentrations of ASCs in adipose tissue can promote Th1-Th2 shifting, and excessive Th2 cells might promote the persistence of M2 macrophages and increase the level of fibrosis which lead to a decrease in the long-term retention of fat grafts. Also, we found ASCs promoted Th1-Th2 shifting in vitro.

Adipose matrix complex: a high-rigidity collagen-rich adipose-derived material for fat grafting.

Due to the low percentage of collagen, the rigid support capacity of fat grafts remains unsatisfactory for some clinical applications. In this study, we evaluated a strategy in which adipose matrix complex (AMC) was collected via a mechanical process and transplanted for supportive filling of the face. Our AMC samples were collected from adipose tissue by a filter device consisting of a sleeve, three internal sieves, and a filter bag (100 mesh). AMC derived from adipose tissue had fewer cells than Coleman fat, but much higher levels of collagen and stiffness. Retention rates 90 days after transplantation in nude mice were higher for AMC than for Coleman fat (75±7.5% vs. 42±13.5%; P < 0.05). In addition, AMC maintained a higher stiffness (~6 kPa vs. ~2 kPa; P < 0.01) and stably retained a higher level of collagen. Our findings demonstrate that mechanical collection of AMC from adipose tissue is a practical method for improving fat graft retention and rigid support. This strategy has the potential to improve the quality of lipoaspirates for patients requiring rigid supportive filling.

Induced Beige Adipocytes Improved Fat Graft Retention by Promoting Adipogenesis and Angiogenesis.

BACKGROUND: Fat grafting is commonly used in treating soft-tissue defects. However, the basic biology behind fat grafting is still not fully understood. Evidence of adipose browning into beige adipose tissue after fat grafting was revealed, but its role in fat grafting remains unclear. METHODS: Induced beige adipocytes and adipose-derived stem cells were obtained from human lipoaspirates and labeled with green fluorescent protein. Nude mice were each injected with 300 mg of human lipoaspirate containing green fluorescent protein-labeled adipose-derived stem cells, green fluorescent protein-labeled induced beige adipocytes, or phosphate-buffered saline. Grafted fat was harvested after 1, 4, 8, and 12 weeks for immunohistochemistry and histologic examination. Graft retention, vascularization, and adipogenic gene expression were compared. RESULTS: After 7 days' induction, adipocytes achieved browning with multilocular lipid droplets, increased mitochondria, and up-regulated browning gene expression. Fat graft retention rates at week 12 were significantly higher after injection of induced beige adipocytes than after injection of phosphate-buffered saline (46.0 ± 4.9 percent versus 31.0 ± 3.6 percent; p = 0.01), but were similar after injection of induced beige adipocytes and adipose-derived stem cells (p > 0.05). Induced beige adipocytes underwent rewhitening into white adipocytes and showed up-regulation of peroxisome proliferator-activated receptor-γ expression. Induced beige adipocytes enhanced angiogenesis, but were not active in forming vessel structures. CONCLUSIONS: Induced beige adipocytes and adipose-derived stem cells were comparable in improving fat graft retention rates. Induced beige adipocytes promote angiogenesis in a paracrine manner and are prone to rewhitening after fat grafting.

Identification of High-Quality Fat Based on Precision Centrifugation in Lipoaspirates Using Marker Floats.

BACKGROUND: Centrifugation creates "graded densities" of fat with varying cellular and biological compositions that influence graft retention. This study aimed to find an accurate method to identify fat fractions that are suitable for implantation. METHODS: Five marker floats (0.925, 0.930, 0.935, 0.940, and 0.945 g/ml) were added to human lipoaspirates that were then centrifuged at 1200 g for 3 minutes to grade the density of centrifuged lipoaspirates. After centrifugation, four fat fractions divided by floats were collected for fat characteristics analysis and in vivo grafting, with Coleman fat as a control. RESULTS: Fat characteristics varied significantly between the centrifuged fat fractions divided by the 0.935-g/ml marker float. Compared with low-quality fat (<0.935 g/ml), high-quality fat (>0.935 g/ml) contains more stromal vascular fraction, adipose-derived stem cells, and extracellular matrix content. Furthermore, adipocytes were found to be significantly smaller in high-quality fat than in low-quality fat, and high-quality fat persisted at a greater volume compared with low-quality fat in vivo at week 12. CONCLUSIONS: High-quality fat contains more stromal vascular fraction cells, extracellular matrix content, and small adipocytes, leading to the highest implant volume retention, whereas low-quality fat contains more fragile large adipocytes, leading to the least volume retention. Marker floats can be used to grade the density of lipoaspirates, with fat greater than 0.935 g/ml recommended as a suitable alternative for implantation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Application of External Force Regulates the Migration and Differentiation of Adipose-Derived Stem/Progenitor Cells by Altering Tissue Stiffness.

Large soft-tissue defects are challenging to reconstruct surgically. Expansion of soft tissue using an external volume expansion (EVE) device is a noninvasive method to improve such reconstruction; however, the underlying mechanism is unclear. In this study, we created fat flaps in Sprague-Dawley rats, applied an external force of 3 or 6 kPa using an EVE device, and investigated the migration and differentiation of adipose-derived stem/progenitor cells (ASCs). In addition, we performed finite element analysis to explore the stiffness of adipose tissue. An external force of 3 kPa promoted the migration and adipogenic differentiation of ASCs. By comparison, an external force of 6 kPa had a larger effect on migration of ASCs, but a smaller effect on adipogenic differentiation of ASCs. External force affected adipose tissue stiffness. In conclusion, external force generated by an EVE device increases the stiffness of adipose tissue, which influences the migration and differentiation of ASCs. The size of the external force can be altered according to the tissue stiffness required at particular time points to promote long-term adipose tissue regeneration. Impact Statement Stem cell therapy in clinic mostly requires the addition of exogenous stem cells, therefore the safety and controllability is always defective. In this study, the external force of external volume expansion regulates adipose-derived stem/progenitor cells (ASCs) migration and differentiation through tissue stiffness. Using tissue engineering without exogenous ASCs can promote long-term adipose tissue regeneration. The findings of this study provide theoretical support for clinical tissue engineering applications and improvements in stem cell therapy.

TGF-ß prevents the denervation-induced reduction of bone formation and promotes the bone regeneration through inhibiting ubiquitin-proteasome pathway.

Background: Transforming growth factor beta (TGF-ß) can stimulate osteogenesis as a multifunctional protein. The present study was to explore if TGF-ß can prevent denervation-induced reduction of bone formation.Materials & methods: The 6-week-old male mice were treated with recombinant human TGF-ß1 (rhTGF-ß1). Bone formation, endochondral bone growth rates, and gene expression of osteoblast markers were measured in the skeletal tissue by real-time PCR.Results: RhTGF-ß1 treatment prevented the denervation-induced decrease in bone formation rates, endochondral growth, and expression of Cbfa1/Runx2 (runt-related transcription factor 2), Ostecalcin (OC), and ColIA1. TGF-ß1 partially inhibited the denervation-induced ubiquitination of Cbfa1/Runx2 in mouse cancellous bones via ubiquitin-proteasome pathway.Conclusion: TGF-ß prevents denervation-induced reduction of bone formation and promotes the bone regeneration through inhibiting ubiquitin-proteasome pathway at least partially.

Validation study of neurotrophin-3-releasing chitosan facilitation of neural tissue generation in the severely injured adult rat spinal cord.

It was previously reported that a tube holding chitosan carriers loaded with neurotrophin-3 (NT-3), after insertion into a 5 mm long transection gap in the adult rat spinal cord, triggered de novo neural tissue generation and functional recovery. Here, we report an effort to validate these findings using stringent blinding methodologies, which are crucial for robustness in reproducing biomedical studies. Radio frequency identification (RFID) chips were utilized to label rats that were randomly assigned into three experimental groups: transection with chitosan-NT-3 implant (C-NT3), transection only (T-controls), and laminectomy only (S-controls), blinding the experimenters to the treatments. Three months after surgery, animals only known by their RFID were functionally, electrophysiologically, and anatomically assessed. The data were then collected into the proper groups and statistically analyzed. Neural tissue with nestin-, Tuj1-, and NeuN-positive cells was found bridging the transection gap in C-NT3 rats, but not in T-controls. Motor- and somatosensory-evoked potentials were detected in C-NT3 rats and S-controls, but not in T-controls. Hind limb movement was significantly better in C-NT3 rats compared with T-controls. Our validation study indicates that C-NT3 implants facilitate neural tissue generation, at least in part, by eliciting endogenous neurogenesis. Our data support the use of C-NT3 implants for tissue remodeling in the injured spinal cord.

Mechanical micronization of lipoaspirates for the treatment of hypertrophic scars.

BACKGROUND: Hypertrophic scars cause cosmetic and functional problems for patients, and their treatment remains challenging. Mechanical micronization of adipose tissue can remove adipocytes and concentrate functional cells. Stromal vascular fraction (SVF)-gel is obtained by a series of simple mechanical processes, including shifting between syringes and centrifugation. This study aimed to assess the therapeutic effect of SVF-gel on hypertrophic scars. METHODS: A model of hypertrophic scars was established in rabbit ears. SVF-gel and SVF cells were obtained from rabbit inguinal fat pads and injected into scars. Phosphate-buffered saline (PBS) was used as a control. Scars were structurally characterized by histologic and immunohistochemical analyses. Expression of inflammatory and fibrogenic genes was evaluated. RESULTS: Hypertrophic scars became less visible and softer following injection of SVF-gel or SVF cells. Dermal thickness was significantly lower in the groups treated with SVF-gel and SVF cells than in the PBS-treated group. Treatment with SVF-gel restored subcutaneous fat tissue in scars, while treatment with SVF cells and PBS did not. Injection of SVF-gel and SVF cells reduced macrophage infiltration in the dermal layer and decreased mRNA expression of interleukin-6 and monocyte chemoattractant protein-1. In addition, the level of myofibroblasts and collagen deposition were reduced in the groups treated with SVF-gel and SVF cells. CONCLUSIONS: SVF-gel has therapeutic effects on hypertrophic scars. Injection of SVF-gel into hypertrophic scars restores subcutaneous fat tissue and reduces the levels of macrophages and myofibroblasts; thus, it decreased the dermal thickness of the scar.