Effects Of Adipose-derived Stem Cells Research Articles

Effect of cell therapy with adipose-derived stem cells in the treatment of acute rupture of the Achilles tendon in humans.

The aim of this study was to evaluate the effect of adipose-derived stem cells (ADSCs) in the treatment of acute rupture of the Achilles tendon. It was a cross-sectional study involving 15 patients. Patients were randomly divided: group 1-rupture; group 2-suture; group 3-rupture + ADSCs. In the AOFAS score, the score was higher in group 3 with a significant difference. In the ATRS score, the score was higher in groups 2 and 3, also with a significant difference. As for the ultrasound score, there was a significant difference between the experimental groups in relation to this score, however, in the multiple comparisons test, comparing two groups at a time, it was possible to observe a significant difference of the experimental groups. It can be concluded that cell therapy in this condition may be a treatment option due to tissue regeneration and significant recovery of function.

Exploring Anti-Fibrotic Effects of Adipose-Derived Stem Cells: Transcriptome Analysis upon Fibrotic, Inflammatory, and Hypoxic Conditioning.

Autologous fat transfers show promise in treating fibrotic skin diseases, reversing scarring and stiffness, and improving quality of life. Adipose-derived stem cells (ADSCs) within these grafts are believed to be crucial for this effect, particularly their secreted factors, though the specific mechanisms remain unclear. This study investigates transcriptomic changes in ADSCs after in vitro fibrotic, inflammatory, and hypoxic conditioning. High-throughput gene expression assays were conducted on ADSCs exposed to IL1-β, TGF-β1, and hypoxia and in media with fetal bovine serum (FBS). Flow cytometry characterized the ADSCs. RNA-Seq analysis revealed distinct gene expression patterns between the conditions. FBS upregulated pathways were related to the cell cycle, replication, wound healing, and ossification. IL1-β induced immunomodulatory pathways, including granulocyte chemotaxis and cytokine production. TGF-β1 treatment upregulated wound healing and muscle tissue development pathways. Hypoxia led to the downregulation of mitochondria and cellular activity.

O124: Investigating the Immuno-modulatory Effect of Adipose-derived Stem Cells in Radiation- Induced Fibrosis

Abstract Background and Introduction Radiation-induced fibrosis (RIF) is a complication of radiotherapy in the treatment of head and neck carcinoma with high patient morbidity. Autologous fat grafting is a viable method to treat RIF, and adipose-derived stem cells (ADSC) were found to be one of the main components to contribute to that effect. Method Experimental group consists of irradiated human-derived fibroblasts (iHDF) in vitro with the control group unexposed to radiation. Both groups were then inoculated with ADSC-controlled media and co-culture with ADSC, whilst levels of key immunomodulators expressed by iHDF cells were obtained and measured via enzyme-linked immunosorbent assay (ELISA) and real-time reverse transcription-polymerase chain reaction (RT-PCR). Results There is marginal decrease in CCL2 concentrations in co-cultured iHDF samples compared to untreated iHDF samples (p = 0.0006). There is a slight increase in CCL3 levels in iHDF co-culture samples compared to untreated iHDF samples (p = 0.0247). iHDF co-culture samples shows a statistically significant increase in IL-8 levels when compared to untreated samples of iHDF (p = 0.027). Col1A1 is reduced in iHDF samples when compared to control groups. Discussion CCL2 is implicated in recruitment of ADSCs to target sites. The increase in IL-8 secretion in ADSC samples is implicated in the pro-angiogenic properties of ADSC secretions to encourage healing in fibrotic tissue. Conclusion ADSC was demonstrated to have anti-fibrotic capabilities by promoting pro- angiogenic factors, however, experimental evidence points to a simultaneous increase in pro-inflammatory factors. Future works required to further investigate in vivo effects of ADSC.

Inhibition of PTEN promotes osteointegration of titanium implants in type 2 diabetes by enhancing anti-inflammation and osteogenic capacity of adipose-derived stem cells.

Background: The low osteogenic differentiation potential and attenuated anti-inflammatory effect of adipose-derived stem cells (ADSCs) from animals with type 2 diabetes mellitus (T2DM) limits osseointegration of the implant. However, the underlying mechanisms are not fully understood. Methods: Western blotting and qRT-PCR analyses were performed to investigate the effects of PTEN on the osteogenic capacity of ADSCs of T2DM rats (TADSCs). We conducted animal experiments in T2DM-Sprague Dawley (SD) rats to evaluate the osteogenic capacity of modified TADSC sheets in vivo. New bone formation was assessed by micro-CT and histological analyses. Results: In this study, adipose-derived stem cells of T2DM rats exhibited an impaired osteogenic capacity. RNA-seq analysis showed that PTEN mRNA expression was upregulated in TADSCs, which attenuated the osteogenic capacity of TADSCs by inhibiting the AKT/mTOR/HIF-1α signaling pathway. miR-140-3p, which inhibits PTEN, was suppressed in TADSCs. Overexpression or inhibition of PTEN could correspondingly reduce or enhance the osteogenic ability of TADSCs by regulating the AKT/mTOR/HIF-1α signaling pathway. TADSCs transfected with PTEN siRNA resulted in higher and lower expressions of genes encoded in M2 macrophages (Arg1) and M1 macrophages (iNOS), respectively. In the T2DM rat model, PTEN inhibition in TADSC sheets promoted macrophage polarization toward the M2 phenotype, attenuated inflammation, and enhanced osseointegration around implants. Conclusion: Upregulation of PTEN, which was partially due to the inhibition of miR-140-3p, is important for the attenuated osteogenesis by TADSCs owing to the inhibition of the AKT/mTOR/HIF-1α signaling pathway. Inhibition of PTEN significantly improves the anti-inflammatory effect and osteogenic capacity of TADSCs, thus promoting peri-implant bone formation in T2DM rats. Our findings offer a potential therapeutic approach for modifying stem cells derived from patients with T2DM to enhance osseointegration.

Exosomes as nanostructures deliver miR-204 in alleviation of mitochondrial dysfunction in diabetic nephropathy through suppressing methyltransferase-like 7A-mediated CIDEC N6-methyladenosine methylation.

The exosomal cargo mainly comprises proteins, lipids, and microRNAs (miRNAs). Among these, miRNAs undertake multiple biological effects of exosomes (Exos). Some stem cell-derived exosomal miRNAs have shown the potential to treat diabetic nephropathy (DN). However, there is little research into the therapeutic effects of adipose-derived stem cell (ADSC)-derived exosomal miRNAs on DN. We aimed to explore the potential of miR-204-modified ADSC-derived Exos to mitigate DN. Exos were extracted and identified from ADSCs. Histopathological injury, oxidative stress (OS), mitochondrial function, cell viability, and apoptosis were assessed to explore the effects of ADSC-derived Exos on DN. For mechanism exploration, quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to measure miR-204, methyltransferase (METTL3, METTL14, and METTL7A), and CIDEC. Also, CIDEC m6A methylation and miR-204-METTL7A, and METTL7A-CIDEC interactions were determined. Initially, OS-induced mitochondrial dysfunction was observed in DN rats. ADSC-derived Exos inhibited histopathological injury, cell apoptosis, OS, and mitochondrial dysfunction in DN rats. The similar therapeutic effects of ADSC-derived Exos were detected in the in vitro model. Intriguingly, miR-204 was released by ADSC-derived Exos and its upregulation enhanced the anti-DN effects of Exos. Mechanically, miR-204 reduced METTL7A expression to CIDEC m6A methylation, thus suppressing OS and mitochondrial dysfunction. ADSC-derived exosomal miR-204 rescued OS-induced mitochondrial dysfunction by inhibiting METTL7A-mediated CIDEC m6A methylation. This study first revealed the significant role of ADSC-derived exosomal miR-204 in DN, paving the way for the development of novel therapeutic strategies to improve the clinical outcomes of DN patients.

Sulfated Chitosan Nanofibrous Scaffolds Seeded With Adipose Stem Cells Promote Ischemic Wound Healing in a Proangiogenic Strategy.

Ischemic wounds are chronic wounds with poor blood supply that delays wound reconstruction. To accelerate wound healing and promote angiogenesis, adipose-derived stem cells (ADSCs) are ideal seed cells for stem cell-based therapies. Nevertheless, providing a favorable environment for cell proliferation and metabolism poses a substantial challenge. A highly sulfated heparin-like polysaccharide 2-N, 6-O-sulfated chitosan (26SCS)-doped poly(lactic-co-glycolic acid) scaffold (S-PLGA) can be used due to their biocompatibility, mechanical properties, and coagent 26SCS high affinity for growth factors. In this study, a nano-scaffold system, constructed from ADSCs seeded on electrospun fibers of modified PLGA, was designed to promote ischemic wound healing. The S-PLGA nanofiber membrane loaded with adipose stem cells ADSCs@S-PLGA was prepared by a co-culture in vitro, and the adhesion and compatibility of cells on the nano-scaffolds were explored. Scanning electron microscopy was used to observe the growth state and morphological changes of ADSCs after co-culture with PLGA electrospun fibers. The proliferation and apoptosis after co-culture were detected using a Cell Counting Kit-8 kit and flow cytometry, respectively. An ischemic wound model was then established, and we further studied the ability of ADSCs@S-PLGA to promote wound healing and angiogenesis. We successfully established ischemic wounds on the backs of rats and demonstrated that electrospun fibers combined with the biological effects of adipose stem cells effectively promoted wound healing and the growth of microvessels around the ischemic wounds. Phased research results can provide a theoretical and experimental basis for a new method for promoting clinical ischemic wound healing.

Long-Term Effects of Adipose-Derived Stem Cells for the Treatment of Bilateral Limbal Stem Cell Deficiency

Purpose To determine the safety and feasibility of human autologous adipose tissue-derived adult mesenchymal stem cells (ASCs) for ocular surface regeneration in patients with bilateral limbal stem-cell deficiency (LSCD). Methods A phase IIa clinical trial was designed (https://Clinicaltrials.gov, NCT01808378) with 8 patients, 3 of whom had aniridia, 2 meibomian glands diseases, 2 multiple surgeries and 1 chronic chemical injury. The therapeutic protocol was as follows: 6-mm of central corneal epithelium was removed, 400,000 ASCs were injected into each limboconjunctival quadrant, 400,000 ASCs were suspended over the cornea for 20 min, and finally the cornea was covered with an amniotic membrane patch. Results No adverse events were detected after a mean of 86,5 months of follow-up. One year after surgery, 6 of the 8 transplants were scored as successful, five patients had improved uncorrected visual acuity (mean of 12 letters), two patients presented epithelial defects (also present at baseline) and the mean percentage of corneal neovascularization was of 28.75% (36.98%, at baseline). Re-examination 24 months after treatment disclosed preserved efficacy in 4 patients. At the last visit (after a mean of 86,5 months of follow up) epithelial defects were absent in all patients although improvement in all of the variables was only maintained in patient 3 (meibomian glands agenesia). Conclusion ASCs are a feasible and conservative therapy for treating bilateral LSCD. The therapeutic effect differs between etiologies and diminishes over time.

Dual Strategy with Adipose-Derived Stem Cells and l-arginine Recovered Cavernosal Functions in a Rat Model of Radical Prostatectomy.

As standard therapy for prostate cancer, radical prostatectomy causes cavernous nerve (CN) injury and increases fibrosis and hypoxia-induced penile structural alterations. This study aimed to determine the potential beneficial effects of adipose-derived stem cells (ADSCs) and l-arginine alone or in combination on the penile erection in a rat model of erectile dysfunction caused by bilateral cavernous nerve transection (CNT). Male rats (n = 35) were randomized into five groups: Sham-operated; CNT (4-weeks); CNT plus ADSCs (1 × 106 cells by intracavernosal injection); CNT plus l-arginine (4 weeks, 10 mg/kg/day, oral); and ADSCs combined with l-arginine in CNT. In vivo erectile responses and in vitro relaxant responses were measured. Western blot and immunohistochemistry analyses were used to determine the expression and localization of endothelial nitric oxide synthase, neuronal nitric oxide synthase, transforming growth factor-beta 1, hypoxia-inducible factor-1 alpha (HIF-1α), and apoptosis markers (Bax and Bcl-2). The ratio of smooth muscle to collagen and nerve regeneration were calculated using Masson's trichrome and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining. The combined treatment restored diminished erectile responses, endothelium-dependent acetylcholine, and electrical field stimulation-induced relaxation of the corpus cavernosum in rats with CNT, whereas either monotherapy produced only partial improvements. All treatment regimens restored increases in the protein expression of HIF-1 and Bax in rats with CNT. The decrease in smooth muscle mass and NADPH-diaphorase-positive nerve fibers was partially ameliorated by monotherapy, whereas combined therapy led to recovery. These findings indicate that combined treatment with ADSCs and l-arginine may restore erectile function in rats with CNT by inhibiting hypoxia-induced neurotoxicity and preserving endothelium function and smooth muscle content.

Therapeutic effect of adipose-derived stem cells injected into pericardial cavity in rat heart failure.

There are few studies on the treatment of heart failure by injecting stem cells into the pericardial cavity. Can the cells injected into the pericardial cavity migrate through the epicardium to the myocardial tissue? Whether there is therapeutic effect and the mechanism of therapeutic effect are still unclear. This study investigated the therapeutic efficacy and evidence of cell migration of adipose-derived stem cells (ADSCs) injected into the pericardial cavity in rat heart failure. The aim of this study is to demonstrate the effectiveness and mechanism of treating heart failure by injecting stem cells into the pericardial cavity, laying an experimental foundation for a new approach to stem cell therapy for heart disease in clinical practice. The inguinal adipose tissue of male SD rats aged 4-6weeks was taken, ADSCs were isolated and cultured, and their stem cell surface markers were identified. Forty rats aged 6-8weeks were divided into sham operation group, heart failure group, and treatment group; there were 15 rats in the heart failure group and 15 rats in the treatment group. The heart failure model was established by intraperitoneal injection of adriamycin hydrochloride. The heart function of the three groups was detected by small animal ultrasound. The model was successful if the left ventricular ejection fraction<50%. The identified ADSCs were injected into the pericardial cavity of rats in the treatment group. The retention of transplanted cells in pericardial cavity was detected by small animal in vivo imaging instrument, and the migration of transplanted cells into myocardial tissue was observed by tissue section and immunofluorescence. Western blotting and immunohistochemical staining were used to detect brain natriuretic peptide (BNP), α-smooth muscle actin (α-SMA), and C-reactive protein (CRP). ADSCs express CD29, CD44, and CD73. On the fourth day after injection of ADSCs into pericardial cavity, they migrated to myocardial tissue through epicardium and gradually diffused to deep myocardium. The cell density in the pericardial cavity remains at a high level for 10days after injection and gradually decreases after 10days. Compared with the heart failure group, the expression of BNP and α-SMA decreased (P<0.05 and P<0.001, respectively), and the expression of CRP in the treatment group was higher than that in the heart failure group (P<0.0001). A small amount of BNP, α-SMA, and CRP was expressed in the myocardium of the sham operation group. After injection of ADSCs, interleukin-6 in myocardial tissue was significantly lower than that in heart failure myocardium (P<0.01). After treatment, vascular endothelial growth factor A was significantly higher than that of heart failure (P<0.01). Pericardial cavity injected ADSCs can penetrate the epicardium, migrate into the myocardium, and have a therapeutic effect on heart failure. Their mechanism of action is to exert therapeutic effects through anti-inflammatory, anti-fibrosis, and increased angiogenesis.

Alternative viewpoint against diabetic wound based on stem cell secretome that can mediated angiogenesis and reduce inflammation.

Diabetes mellitus, as an important metabolic disorder, affects the health of millions of people worldwide. A diabetic wound is one of the complications of diabetes. The stem cell secretome can particularly affect the wound healing process in diabetic wounds. The present study aimed to investigate the effects of Adipose-derived stem cells (ASCs) secretome on the skin wound healing process, angiogenesis, and inflammation in diabetic rats. For this purpose, ASCs were extracted from Adipose tissue and confirmed by flow cytometry and cell differentiation. Secretome was prepared. 27 rats were divided into three groups, non-diabetic, diabetic (treated with phosphate-buffered saline), and diabetics treated with secretome. The levels of vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-β) were examined by the enzyme-linked immunosorbent assay (ELISA) was performed in the skin tissues of all groups. Hematoxylin and eosin (H&E) staining was performed. The level of VEGF was higher in the diabetic group treated with secretome as compared to the other two groups, while the level of TGF-β was lower in this group, compared to the diabetic group. Based on the results of H&E staining, the epidermal thickness and angiogenesis were higher in the diabetic group treated with secretome, whereas edema, number of inflammatory cells, and epidermal damage were lower in this group, compared to the diabetic group. Subcutaneous injection of secretome can lead to diabetic wound healing by increasing growth factors associated with angiogenesis such as VEGF, increasing angiogenesis, regulating TGF-β levels, reducing inflammatory cells.

Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-β1/Smad 3 signaling pathway.

To investigate the effect of adipose-derived stem cells (ASCs) transplantation on radiation-induced lung injury (RILI), Sprague-Dawley rats were divided into phosphate-buffered saline (PBS) group, ASCs group, Radiation + PBS group, and Radiation + ASCs group. Radiation + PBS and Radiation + ASCs groups received single dose of 30 Gy X-ray radiation to the right chest. The Radiation + PBS group received 1 mL PBS suspension and Radiation + ASCs group received 1 mL PBS suspension containing 1 × 107 CM-Dil-labeled ASCs. The right lung tissue was collected on Days 30, 90, and 180 after radiation. Hematoxylin-eosin and Masson staining were performed to observe the pathological changes and collagen fiber content in the lung tissue. Immunohistochemistry (IHC) and western blot (WB) were used to detect levels of fibrotic markers collagen I (Collal), fibronectin (FN), as well as transforming growth factor-β1 (TGF-β1), p-Smad 3, and Smad 3. Compared with the non-radiation groups, the radiation groups showed lymphocyte infiltration on Day 30 after irradiation and thickened incomplete alveolar walls, collagen deposition, and fibroplasia on Days 90 and 180. ASCs relieved these changes on Day 180 (Masson staining, P = 0.0022). Compared with Radiation + PBS group, on Day 180 after irradiation, the Radiation + ASCs group showed that ASCs could significantly decrease the expressions of fibrosis markers Collal (IHC: P = 0.0022; WB: P = 0.0087) and FN (IHC: P = 0.0152; WB: P = 0.026) and inhibit the expressions of TGF-β1 (IHC: P = 0.026; WB: P = 0.0152) and p-Smad 3 (IHC: P = 0.0043; WB: P = 0.0087) in radiation-induced injured lung tissue. These indicated that ASCs could relieve RILI by inhibiting TGF-β1/Smad 3 signaling pathway.

Effect of adipose-derived stem cells seeding and surgical prefabrication on composite scaffold vascularization.

The study aimed to evaluate an angiogenic effect of adipose-derived stem cells (ASCs) seeding and surgical prefabrication (placing a vascular pedicle inside the scaffold) on developed composite scaffolds made of poly-ε-caprolactone (PCL), β-tricalcium phosphate (β-TCP), and poly (lactic-co-glycolic acid) (PLGA) (PCL+β-TCP+PLGA). Moreover, we aimed to compare our data with previously tested PCL scaffolds to assess whether the new material has better angiogenic properties. The study included 18 inbred male WAG rats. There were three scaffold groups (six animals each): with non-seeded PCL+β-TCP+PLGA scaffolds, with PCL+β-TCP+PLGA scaffolds seeded with ASCs and with PCL+β-TCP+PLGA scaffolds seeded with ASCs and osteogenic-induced. Each rat was implanted with two scaffolds in the inguinal region (one prefabricated and one non-prefabricated). After 2months from implantation, the scaffolds were explanted, and vessel density was determined by histopathological examination. Prefabricated ASC-seeded PCL+β-TCP+PLGA scaffolds promoted greater vessel formation than non-seeded scaffolds (19.73 ± 5.46 vs 12.54 ± 0.81; p = .006) and those seeded with osteogenic-induced ASCs (19.73 ± 5.46 vs 11.87±2.21; p = .004). The developed composite scaffold promotes vessel formation more effectively than the previously described PCL scaffold.

Effect of adipose derived stem cells on the survival rate of long random pattern skin flap in rats, and the underlying mechanism of action

Purpose: To investigate the effect of adipose-derived stem cells (ADSCs) on the survival rate of long random pattern skin flaps in rats and the likely underlying mechanism.&#x0D; Methods: Twenty (20) SPF-grade SD rats were randomly divided into control group and study group, with 10 rats in each group. Rats in the control group were given phosphate buffered saline (PBS), while rats in the study group received ADSCs. The survival rate of the skin flaps was compared between the 2 groups on day 7 after operation, while the levels of indices related to oxidative stress and inflammatory response were compared on the 7th and 14th days after operation.&#x0D; Results: Necrosis in the study group was milder (p &lt; 0.05). On the 7th post-operation day, the survival rate of rat skin flap in the study group was significantly higher than that in the control group (p &lt; 0.05), but the MDA level in the study group was lower than that of the control group (p &lt; 0.05). On the 14th day after the operation, the MDA level was decreased in the two groups (p &lt; 0.05), with a lower MDA level in the study group than in the control group (p &lt; 0.05).&#x0D; Conclusion: ADSCs inhibit inflammatory response and reduces the level of oxidative stress after long random pattern skin flap transplantation in rats, thereby enhancing blood supply to the flap transplantation area and improving its survival rate. Thus, ADSCs have a potential clinical application in enhancing blood supply in skin transplantation.

Melatonin pretreatment can improve the therapeutic effect of adipose-derived stem cells on CCl4-induced liver fibrosis

In this study, the therapeutic effect of Mel-incubated Adipose-derived mesenchymal stem cells (ADSCs) on CCl4-induced hepatic fibrosis was investigated. Mice with hepatic fibrosis were intraperitoneally injected with 8% CCl4 twice a week for 4 weeks. Starting from week 5, mice in the ADSC group and ADSC + Mel group were injected with 1 mL PBS cell suspension containing 1 × 106 ADSCs or ADSCs pretreated with 50 nM Mel twice a week for 2 consecutive weeks. Results: In the model group, severe histopathological changes were observed in the liver, including severe vacuolation, nuclear fragmentation, and liver fibrosis, and these changes were ameliorated by Mel-pretreated ADSCs. RT-qPCR results showed that Mel-induced ADSCs significantly inhibited the expression of proapoptotic genes (Caspase-8, Bax, and Caspase-3) and promoted the expression of an anti-apoptotic gene (Bcl-2). Immunohistochemical results showed that a large number of MMP-9-, TGF-β-, and MMP-2-positive cells were present in the liver tissues of the model group, while the number of positive cells was reduced by Mel-induced ADSCs. ELISA results showed that the ADSC pretreated with Mel also significantly reduced the expression levels of TNF-α and IL-6. Conclusion: ADSCs pretreated with Mel significantly improved CCl4-induced liver fibrosis.

Autologous Fat Grafting in Female Genital Area Improves Sexual Function by Increasing Collagenesis, Angiogenesis, and Estrogen Receptors.

Vulvovaginal laxity, atrophic vaginitis, and orgasmic dysfunction are not only aesthetic but also sexual problems. Autologous fat grafting (AFG) facilitates tissue rejuvenation through the effects of adipose-derived stem cells; the fat grafts serve as soft-tissue filler. However, few studies have reported the clinical outcomes of patients undergoing vulvovaginal AFG. The aim of this study was to describe a new technique, micro-autologous fat transplantation (MAFT), for AFG in the vulvovaginal area. Posttreatment histologic changes in the vaginal canal that imply improved sexual function were assessed. This retrospective study enrolled females who underwent vulvovaginal AFG performed through MAFT between June 2017 and 2020. Assessments were based on the Female Sexual Function Index (FSFI) questionnaire and on histologic and immunohistochemical staining. In total, 20 female patients (mean age, 38.1 years) were included. On average, 21.9 mL of fat was injected into the vagina and 20.8 mL in the vulva and mons pubis area. Six months afterwards, the patients' mean total FSFI score (68.6) was significantly higher than that at baseline (43.8; P < .001). Histologic and immunohistochemical staining of vaginal tissues revealed substantially increased levels of neocollagenesis, neoangiogenesis, and estrogen receptors. By contrast, the level of protein gene product 9.5, which is associated with neuropathic pain, was considerably lower after AFG. AFG performed through MAFT in the vulvovaginal area may help manage sexual function-related problems in females. In addition, this technique improves aesthetics, restores tissue volume, alleviates dyspareunia with lubrication, and reduces scar tissue pain.

Enhancing the paracrine effects of adipose stem cells using nanofiber-based meshes prepared by light-welding for accelerating wound healing

The interaction between electrospinning nanomaterials and stem cells to repair damaged tissue mainly focus on manipulating cell viability, proliferation, or paracrine by the materials and their specific topology. In particular, the paracrine products of stem cells influence the behavior of those repairable cells (i.e., epidermal cells, fibroblasts, and endothelial cells) to speed up the repair progress. In this study, a series of nanofiber-based meshes were fabricated by electrospinning and light-welding technology to investigate their impacts on the paracrine behaviors of adipose stem cells (ADSCs) and their performance in accelerating wound healing. We found that the nanofiber-based meshes with varied grid sizes and modified with gelatin nanofibers could regulate the paracrine of ADSCs. As a result, the migration of fibroblasts and endothelial cells as well as angiogenesis was all influenced in vitro. In vivo investigation using rat skin wound healing models also indicated that the nanofiber-based meshes could accelerate wound healing rate, increase the thickness of the regenerated epidermis, and promote type I collagen production and CD31-positive vessel formation in the dermis layer. Taken together, such nanofiber-based meshes provide effective and promising alternatives to design tissue-repair scaffolds involving manipulating stem cell paracrine and wound closure.

Adipocytes secretome from normal and tumor breast favor breast cancer invasion by metabolic reprogramming.

Adipose tissue is a major component of breast stroma. This study focused on delineating the effects of adipose stem cells (ASCs) derived from breast of healthy women and cancer patients with normal or tumor breast cells. The ASCs were induced to differentiate into adipocytes, and the subsequent adipocyte conditioned media (ACM) were evaluated for their fatty acid profile, adipokine secretion and influence on proliferation, migration and invasion on tumoral (MCF-7 and SUM159) and normal (HMEC) human breast cell lines. An enrichment of arachidonic acid was observed in ACM from tumor tissues. Adipose tissues from tumor free secrete twice as much leptin than those from proximal or distal to the tumor. All ACMs display proliferative activity and favor invasiveness of SUM159 cells compared to MCF-7 and HMEC. All ACMs induced lipid droplets accumulation in MCF-7 cells and increased CD36 expression in tumor cells. We conclude that among secreted factors analyzed, only arachidonic acid and leptin levels did discriminate ASCs from tumor-bearing and tumor-free breasts emphasizing the importance that other cell types could contribute to the adipose tissue secretome in a tumor context.

Retrospective Study on the Effect of Adipose-Derived Stem Cells on the Proliferation and Apoptosis of Keloid Fibroblasts Through the Suppression of ITGA2.

Keloid is characterized by excessive collagen accumulation and fibroblast growth, which are fibroproliferative disorders of injured skin, causing functional limitations. Studies have shown that adipose-derived stem cells (ADSCs) inhibit the bioactivity and fibrosis of keloid fibroblasts. However, the molecular mechanism of this effect of ADSCs on keloid formation has not been fully elucidated. This in vitro study used fibroblasts obtained from keloids. A consensus gene co-expression network was constructed to focus on identifying consensus gene co-expression modules associated with keloid fibroblasts. Differentially expressed genes (DEGs) were identified between keloid fibroblasts and normal dermal fibroblasts. A functional enrichment analysis was also performed with the DAVID database. A weighted gene co-expression network analysis (WGCNA) was used to screen keloid-related modules using the "WGCNA" R package, followed by hub gene selection in modules from the Protein-protein interaction network through the STRING database. Keloid fibroblasts and ADSCs were extracted and cultured. Proliferation and apoptosis were examined using a 5-ethynyl-2-deoxyuridine (Edu) kit and flow cytometry. We identified 302 DEGs overlapping with a consensus analysis of clusters and a differential expression analysis between keloid fibroblasts and normal dermal fibroblasts. Most of these were involved in collagen binding, extracellular matrix organization, and the PI3K-Akt signaling pathway. WGCNA analysis selected a keloid-associated brown module. ITGA2 was identified as a novel marker in hub genes from the PPI network based on the degree and function of collagen modulation. Furthermore, the proliferation ability of keloid fibroblasts cultured in ADSC medium was inhibited while apoptosis was dramatically increased. Overexpression of ITGA2 reversed the decrease in ADSC-induced apoptosis and increased ADSC-reduced proliferation. Our study demonstrated that activation of ITGA2 plays a crucial role in ADSC-induced keloid fibroblast apoptosis and anti-proliferation effects. These results also improved our understanding of the molecular mechanism of the pathogenesis of keloid in response to ADSCs and may contribute to the further development of keloid therapy.

Adipose-Derived Stem Cells Attenuate Skin Fibrosis and Improve Fat Retention of a Localized Scleroderma Mouse Model.

Although autologous fat grafting is a feasible surgical technique to improve facial deformity in patients with localized scleroderma, its success is limited by the low graft retention induced by the local inflammatory environment. This study investigated the potential effect of adipose-derived stem cells (ASCs) on skin fibrosis and fat retention in a localized scleroderma mouse model. BALB/C nude mice that were induced by bleomycin to establish a localized scleroderma model were divided randomly into five groups: blank control; fat grafting; and low, moderate, and high doses of ASC-assisted fat grafting. The backs of the mice were subcutaneously injected with phosphate-buffered saline or fat, or fat with low, moderate, and high doses of ASCs (1 × 10 5 /mL, 5 × 10 5 /mL, and 25 × 10 5 /mL, respectively). The skin fibrosis and fat retention were analyzed after 1 month or 3 months, respectively. Compared to the disease model group, the fat-grafting group, and the low- and moderate-dose ASC-enriched groups, the high-dose ASCs significantly attenuated skin fibrosis, inhibited the production of type III collagen and transforming growth factor-β1, increased fat graft retention, enhanced the expression of angiogenesis-related cytokines and angiogenesis, and increased the expression of adipogenesis-related cytokines. The results demonstrated that high-dose ASCs attenuated skin fibrosis and improved fat retention in a localized scleroderma model by reducing inflammation and by promoting angiogenesis and adipogenesis. The authors further demonstrated that ASCs enhanced adipogenesis through the AKT/ERK signaling pathway. Fat grafting has been used to treat localized scleroderma patients but with low fat retention. In this study, ASC attenuated skin fibrosis and improved fat retention in the localized scleroderma model, providing evidence for cell therapy in future application of localized scleroderma treatment.

The Immunomodulatory Effect of Adipose-Derived Stem Cells in Xenograft Transplantation Model

Adipose-derived stem cells (ASCs) have demonstrated immunomodulatory and anti-inflammatory effects in preclinical studies. The purpose of this study was to evaluate the effects of ASCs on the survival of xenogeneic full-thickness skin grafts and compare intravenous and subcutaneous injections of ASCs. We divided 30 male C57BL/6 mice into control, intravenous (IV), and subcutaneous (SC) injection groups. In one group of 10 mice, mouse ASCs were intravenously injected after human full-thickness skin grafting (IV group). In another group of 10 mice, ASCs were directly injected into the subcutaneous plane under the xenogeneic grafts (SC group). An additional group of 10 mice received no treatment and served as controls. Bioluminescent imaging showed that ASCs were concentrated at the grafts during the study period in both IV and SC groups. We performed graft survival assessment, histologic examination, and immunohistochemistry analysis. ASCs significantly prolonged xenograft survival at postoperative week 2 in the SC group compared with the control group (P < .05). Histologic evaluation revealed fewer inflammatory reactions in the SC group than in the control group at 1 week posttransplantation. In addition, we observed relative reduction in CD4- and CD8-positive cells in the SC group compared with the control group. Intravenous injection of ASCs led to increased graft survival and decreased inflammatory reactions, but these differences were not statistically significant. The results of this study indicate that subcutaneous injection of ASCs promoted the survival of xenogeneic full-thickness skin grafts in mice. The underlying mechanisms of the immunosuppressive effects of ASCs should be further investigated.