Autologous Adipose-derived Mesenchymal Stem Cells Research Articles

MicroRNA-155 mediates multiple gene regulations pertinent to the role of human adipose-derived mesenchymal stem cells in skin regeneration.

Introduction: The role of Adipose-derived mesenchymal stem cells (AD-MSCs) in skin wound healing remains to be fully characterized. This study aims to evaluate the regenerative potential of autologous AD-MSCs in a non-healing porcine wound model, in addition to elucidate key miRNA-mediated epigenetic regulations that underlie the regenerative potential of AD-MSCs in wounds. Methods: The regenerative potential of autologous AD-MSCs was evaluated in porcine model using histopathology and spatial frequency domain imaging. Then, the correlations between miRNAs and proteins of AD-MSCs were evaluated using an integration analysis in primary human AD-MSCs in comparison to primary human keratinocytes. Transfection study of AD-MSCs was conducted to validate the bioinformatics data. Results: Autologous porcine AD-MSCs improved wound epithelialization and skin properties in comparison to control wounds. We identified 26 proteins upregulated in human AD-MSCs, including growth and angiogenic factors, chemokines and inflammatory cytokines. Pathway enrichment analysis highlighted cell signalling-associated pathways and immunomodulatory pathways. miRNA-target modelling revealed regulations related to genes encoding for 16 upregulated proteins. miR-155-5p was predicted to regulate Fibroblast growth factor 2 and 7, C-C motif chemokine ligand 2 and Vascular cell adhesion molecule 1. Transfecting human AD-MSCs cell line with anti-miR-155 showed transient gene silencing of the four proteins at 24h post-transfection. Discussion: This study proposes a positive miR-155-mediated gene regulation of key factors involved in wound healing. The study represents a promising approach for miRNA-based and cell-free regenerative treatment for difficult-to-heal wounds. The therapeutic potential of miR-155 and its identified targets should be further explored in-vivo.

Improvement of endometrial thickness and in vitro fertilization outcomes in patients with Asherman's refractory endometrium using autologous mesenchymal stem cells from the stromal vascular fraction.

Patients with Asherman's Syndrome (AS) and an endometrial thickness (EMT) less than 7 mm are infertile women with suboptimal endometrium due to uterine scarring or endometrial atrophy. This study aimed to examine the effect of intrauterine injections of adipose-derived mesenchymal stem cells (ADMSC) from the Stromal Vascular Fraction (SVF) of adipose tissue on EMT and in vitro fertilization (IVF) outcomes: which are improvements in EMT and pregnancy rates. This double-arm retrospective study included 41 AS patients with hysteroscopic adhesiolysis. Twenty-one patients with AS refractory endometrium (Group 2) were given ADMSC to improve EMT, and 20 non-treated, age-matched patients served as controls (Group 1). For Group 2, SVF was isolated from 15 ml of adipose tissue and transmyometrial injected into the patient's uterine cavity. For all patients, EMT was examined using ultrasound before embryo transfer. In Group 2, after ADMSC treatment, EMT significantly improved (3.2 ± 1.8 mm, P<0.001). Afterward, three patients spontaneously became pregnant, and eighteen underwent frozen embryo transfer. A significant increase in implantation (66.7% vs. 4.8%, P = 0.002) and live birth rates (0.0% vs. 47.6%, P = 0.001) were recorded. No significant difference was observed in EMT, cycle implantation, or clinical pregnancy between the two groups, but the live birth rate in Group 2 after ADMSC treatment was higher than in Group 1. The results demonstrate that autologous intrauterine ADMSC injection can improve EMT, implantation, and pregnancy rates in AS patients with refractory endometrium. This research underscores the life-changing potential of autologous ADMSC treatment for patients with refractory endometrium, providing a promising avenue for future treatments.

Injection of Freshly Collected Adipose Tissue for the Treatment Complex Cryptoglandular Anal Fistula: Case Report

AbstractIntroduction Perianal fistula is a common colorectal disease which is caused mainly by cryptoglandular disease. Although most cases are treated successfully by surgery, management of complex perianal fistulas (CPAF) remains a challenge with limited results in recurrence and sometimes associated with fecal incontinence. The CPAF treatment with autologous adipose-derived mesenchymal stem cells (ASCs) had become a research hotspot. The technique started to be used in the treatment of Crohn's disease (CD) fistulas, where the studies showed safe and goods result from the procedure. Cultured ASCs have been used but this approach requires the preceding collection of adipose tissue, time for isolation of ASCs and subsequent in vitro expansion, need for laboratory facilities, and expertise in cell culturing. These factors have been getting over by using the commercially available alternative, allogenic ASCs. Treatment with allogeneic ASCs has shown good results in patients with CD fistulas, however with the disadvantage of being expensive. Objective To show that the injection with freshly collected adipose tissue is an alternative to treatment with autologous or allogenic ASCs with several advantages. Methods: In this case report, we show our first experience in the treatment of CPAF with the application of collected adipose tissue in a tertiary referral hospital from Belo Horizonte, Brazil. Results The patient had a good postoperative recuperation with a complete fistula healing after 8 months without adverse effects. Conclusion Injection with freshly collected adipose tissue is a promising and apparently safe sphincter-sparing technique in the treatment of CPAF.

Use of autologous adipose-derived mesenchymal stem cells for ovarian rejuvenation in poor responder IVF patients: a phase 1 randomized placebo-controlled double-blind crossover study

Background: Despite the application of various methods to augment ovarian responsiveness, the management of poor ovarian responders remains challenging and pregnancy rates following in vitro fertilization are poor. Advances in adult stem cell research and their clinical application has prompted interest in their use in assisted reproduction. We report the first double-blind, randomized, placebo-controlled clinical study using autologous human stromal vascular fraction (SVF) containing adipose-derived stem cells (ADSCs) for ovarian rejuvenation. Materials and methods: Thirty patients were recruited. Twenty-one had lower-than-expected reserves for their age and 9 had premature ovarian insufficiency. Patients were randomized into a placebo group (10) and an intervention group (20). SVF was obtained from adipose tissue following abdominal liposuction; the ADSC component was characterized using flow cytometry. Three equal insertions, adjusted based on ovarian volume, were performed at monthly intervals via an ultrasound-guided transvaginal needle puncture. The SVF was not cultured before transplantation. Those in the placebo group were then crossed over to the intervention group and received a single SVF (maximally concentrated) insertion (crossover group). Results: The median viable SVF cell number inserted per patient over 3 months, and the percentage of mesenchymal stem cells (MSC) thereof, was 1.6×106 and 13.2%, respectively. Resulting anti-Mullerian hormone (AMH) changes were variable over the treatment course with a notable placebo effect. Patients with premature ovarian insufficiency showed no change in AMH, both to intervention and placebo. Despite this, a temporary return of menses was noted in a third of patients while on treatment. Patients with low reserves for age showed an increase in AMH, although not statistically significant when compared to placebo. In the crossover group, insertions were limited to one intervention comprising all cells; here a significantly higher median of 3.4×106 SVF cells were injected containing an average of 16.9% MSCs. No significant change in AMH was noted. To date 12 patients have undergone ovarian stimulation and in vitro fertilization after stem cell therapy; of these 9 have had embryo transfers with a resulting pregnancy rate of 33%. There were also 2 spontaneous pregnancies. Conclusion: Although the application of SVF-derived ADSCs for ovarian rejuvenation remains experimental, the current study provides further support for the safety of this approach and presents encouraging results as to its efficacy in assisted reproduction.

Clinical Efficacy and Safety of the Intra-articular Injection of Autologous Adipose-Derived Mesenchymal Stem Cells for Knee Osteoarthritis: A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial

Background: Intra-articular injection of autologous culture-expanded adipose-derived mesenchymal stem cells (ADMSCs) has introduced a promising treatment option for knee osteoarthritis. Although the clinical efficacy and safety of ADMSCs have been reported, the treatment remains controversial owing to the small sample sizes and heterogeneous osteoarthritis grades in previous studies. Purpose: To assess the efficacy and safety of intra-articular injection of ADMSCs as compared with placebo in alleviating pain and improving functional capacity in a large sample of patients with knee osteoarthritis of Kellgren-Lawrence (K-L) grade 3. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: This phase III multicenter clinical trial was a double-blind randomized controlled study that included 261 patients with K-L grade 3 symptomatic knee osteoarthritis who were administered a single injection of autologous culture-expanded ADMSCs or placebo. Clinical data were assessed at baseline and at 3 and 6 months after the injection. The primary endpoints were improvements in 100-mm visual analog scale (VAS) for pain and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for function at 6 months after the injection. The secondary endpoints included clinical and radiologic examinations and safety after injection. The changes in cartilage defects after injection were assessed by magnetic resonance imaging at 6 months. Results: The ADMSC and control groups included 125 and 127 patients available for follow-up, respectively. At 6 months, the ADMSC group showed significantly better improvements in 100-mm VAS (ADMSC vs control, 25.2 vs 15.5; P = .004) and total WOMAC score (21.7 vs 14.3; P = .002) as compared with the control group. The linear mixed model analysis indicated significantly better improvements in all clinical outcomes in the ADMSC group after 6 months. At 6 months, the ADMSC group achieved significantly higher proportions of patients above the minimal clinically important difference in 100-mm VAS and WOMAC score. Radiologic outcomes and adverse events did not demonstrate significant differences between the groups. No serious treatment-related adverse events were observed. Magnetic resonance imaging revealed no significant difference in change of cartilage defects between the groups at 6 months. Conclusion: Intra-articular injection of autologous culture-expanded ADMSCs provided significant pain relief and functional improvements in patients with K-L grade 3 osteoarthritis. Long-term results are needed to determine the disease-modifying effects of ADMSCs, such as structural changes, and the duration of effect of intra-articular injection of ADMSCs in knee osteoarthritis. Registration: NCT03990805 (ClinicalTrials.gov identifier).

Autologous adipose-derived mesenchymal stem cell therapy reverses detrusor underactivity: open clinical trial

BackgroundDetrusor underactivity is a disease that can cause chronic urinary tract infection, urinary tract infection, urinary retention and kidney failure and has no effective treatment in traditional medicine. The present research evaluated the effects of cell therapy with adipose tissue-derived stem cells on the treatment of detrusor underactivity in men.MethodsNine male patients diagnosed with a clinical and urodynamic diagnosis of detrusor underactivity were evaluated and underwent two transplants via cystourethroscopy, with 2 × 106 cells/transplant, performed by intravesical injection at five points on the bladder body above the vesical trigone.ResultsCell therapy increased the maximum flow from 7.22 ± 1.58 to 13.56 ± 1.17, increased the mean flow from 3.44 ± 0.74 to 5.89 ± 0.45, increased the urinated volume from 183.67 ± 49.28 to 304.78 ± 40.42 and reduced the residual volume in the uroflowmetry exam from 420.00 ± 191.41 to 118.33 ± 85.51; all of these changes were significant (p < 0.05). There were also significant increases (p < 0.05) in maximum flow (from 7.78 ± 0.76 to 11.56 ± 1.67), maximum detrusor pressure (from 20.22 ± 8.29 to 41.56 ± 5.75), urinary volume (from 244 ± 27.6 to 418.89 ± 32.73) and bladder contractility index (from 44.33 ± 4.85 to 100.56 ± 8.89) in the pressure flow study. Scores on the International Consultation on Incontinence Questionnaire decreased from 11.44 ± 1.43 to 3.78 ± 0.78 after cell therapy, which indicates an improvement in quality of life and a return to daily activities. No complications were observed in the 6-month follow-up after cell therapy. Before treatment, all patients performed approximately five intermittent clean catheterizations daily. After cell therapy, 7/9 patients (77.78%) did not need catheterizations, and the number of catheterizations for 2/9 patients (22.28%) was reduced to two catheterizations/day.ConclusionsThe results indicate that stem cell therapy led to improvements in voiding function. Cell therapy with adipose tissue-derived stem cells is safe and should be considered a new therapeutic option for the treatment of detrusor underactivity.Trial registration ISRCTN, ISRCTN23909398; Registered 15 March 2021—Retrospectively registered, https://doi.org/10.1186/ISRCTN23909398

Urinary Bladder Patch Made with Decellularized Vein Scaffold Seeded with Adipose-Derived Mesenchymal Stem Cells: Model in Rabbits.

To evaluate tissue regeneration of the urinary bladder after the implantation of a decellularized vein sown with autologous adipose-derived mesenchymal stem cells (ASC) on luminal surfaces. New Zealand rabbits (n = 10) were distributed in two groups: Group Bioscaffold alone (G1)-decellularized vena cava (1 cm2) was implanted, and Group Bioscaffold plus ACSs (G2)-decellularized vena cava (1 cm2) containing ASCs were implanted. ASCs were expanded, characterized, and maintained for one week in culture with a decellularized vein scaffold. The implants were performed under general anesthesia using a continuous suture pattern. Afterward, 21 d (day) specimens were collected and analyzed by hematoxylin and eosin (HE) histology and scanning electron microscopy (SEM). The integrity of the urinary bladder was maintained in both groups. A superior regenerative process was observed in the G2 group, compared to the G1 group. We observed a greater urothelial epithelialization and maturity of the mucosa and submucosa fibroblasts. Furthermore, SEM demonstrated a notable amount of urothelial villus in the G2 group. Decellularized vena cava scaffolds were able to maintain the integrity of the urinary bladder in the proposed model. In addition, ASCs accelerated the regenerative process development, observed primarily by the new urothelial epithelization and the maturity of mucosa and submucosa fibroblasts.

Autologous Adipose-Derived Mesenchymal Stem Cell Transplantation for Management of Chronic Kidney Disease Patients: A Clinical Trial in Human

The current clinical trial presents a review of CKD-patients enrolled for Autologous Adipose-Derived Mesenchymal Stem Cells (adMSCs) transplantation at Bangladesh Laser &amp; Cell Surgery (BLCS) Institute &amp; Hospital. Between April 2019 to June 2021, 52 CKD-patients were enrolled in this phase 1 &amp; 2 trial receiving intravenous autologous adMSCs transplantation. Twenty-three CKD-patients who had received MSCs transplantation and had also followed-up with di-ethylene tri-amine Penta-acetic acid (DTPA) -based glomerular filtration rate (GFR) assessment, were considered for analysis. The mean (SD) DTPA-based GFR was significantly improved after adMSCs transplantation among study participants than the baseline mean (SD) DTPA-based GFR (19.79 [12.4] vs 15.07 [11.4], p=0.003). The DTPA-based GFR improved in stage-5 CKD patients with and without dialysis after MSCs transplantation, but a significant mean difference was observed only in CKD patients on dialysis (7.1 [6.9] vs 14.2 [12.6], p=0.011). Hence, pre-dialysis patients DTPA-GFR both at baseline and endline was higher than patients those on dialysis. The obtained results revealed that renal function improves in CKD patients through MSCs transplantation. No significant side effects or complication pertaining specifically to stem cell transplantation was observed during the study period.

3D bioprinting of multilayered scaffolds with spatially differentiated ADMSCs for rotator cuff tendon-to-bone interface regeneration

Regeneration of the gradient structure of the tendon-to-bone interface is still a significant clinical challenge. This study reports a novel therapeutic method combining three-dimensional (3D) bioprinting and melt electrospinning writing techniques to regenerate a functional tendon-to-bone interface. We generated biomimetic multilayered scaffolds with 3D-bioprinted pre-differentiated autologous adipose-derived mesenchymal stem cells (ADMSC), which recapitulated compositional and cellular structures of the interface. The hydrogel-based bioinks offered high cell viability and proliferative capability for rabbit ADMSCs. The hydrogels with pre-differentiated (into tenogenic, chondrogenic, and osteogenic lineages) or undifferentiated rabbit ADMSCs were 3D-bioprinted into zonal-specific constructs to mimic the structure of the tendon-to-bone interface. These scaffolds were tested in a rabbit rotator cuff injury model and the histological, radiological, and biomechanical changes were analyzed. The in vivo studies demonstrated that the scaffold with spatially differentiated autologous ADMSCs had a superior histological score and improved collagen organization when compared to acellular scaffolds and similar T2 value as the normal interface tissue. The biomechanical characterization demonstrated that the application of multilayered scaffolds improved the biomechanical properties of the tendon-to-bone interface at 12 weeks after rotator cuff reconstruction surgery, but the incorporation of autologous ADMSCs within the multilayered scaffolds showed a limited contribution. Thus, our work provides a 3D-bioprinting-based strategy with the application of autologous ADMSCs to reconstruct massive rotator cuff tendon tears.

Low-dose mesenchymal stem cell therapy for discogenic pain: safety and efficacy results from a 1-year feasibility study.

Aim:To evaluate safety and efficacy of low dose autologous adipose-derived mesenchymal stem cells (ADMSCs) for treatment of disc degeneration resulting in low back pain (LBP).Methods:Nine participants with chronic LBP originating from single-level lumbar disc disease underwent intradiscal injection of 10 million ADMSCs with optional repetition after 6 months.Results:No unexpected or serious adverse events were recorded. Seven (78%) of participants reported reductions in pain 12 months after treatment. Five (56%) reported increased work capacity. Three (33%) reduced analgesic medication. Improvements in EQ-5D and Oswestry disability index results were observed. MRI demonstrated no further disc degeneration and improvements to annular fissures and disc protrusions.Conclusion:This study provides initial evidence of safety and efficacy of ADMSCs for discogenic LBP.

Normal ex vivo mesenchymal stem cell function combined with abnormal immune profiles sets the stage for informative cell therapy trials in idiopathic pulmonary fibrosis patients

BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic, progressive pulmonary disease characterized by aberrant tissue remodeling, formation of scar tissue within the lungs and continuous loss of lung function. The areas of fibrosis seen in lungs of IPF patients share many features with normal aging lung including cellular senescence. The contribution of the immune system to the etiology of IPF remains poorly understood. Evidence obtained from animal models and human studies suggests that innate and adaptive immune processes can orchestrate existing fibrotic responses. Currently, there is only modest effective pharmacotherapy for IPF. Mesenchymal stem cells (MSCs)-based therapies have emerged as a potential option treatment of IPF. This study characterizes the functionality of autologous MSCs for use as an IPF therapy and presents an attempt to determine whether the disease occurring in the lungs is associated with an alterated immune system.MethodsComprehensive characterization of autologous adipose-derived MSCs (aMSCs) from 5 IPF patient and 5 age- and gender-matched healthy controls (HC) was done using flow cytometry, PCR (ddPCR), multiplex Luminex xMAP technology, confocal microscopy self-renewal capacity and osteogenic differentiation. Additionally, multi-parameter quantitative flow cytometry of unmanipulated whole blood of 15 IPF patients and 87 (30 age- and gender-matched) HC was used to analyze 110 peripheral phenotypes to determine disease-associated changes in the immune system.ResultsThere are no differences between autologous aMSCs from IPF patients and HC in their stem cell properties, self-renewal capacity, osteogenic differentiation, secretome content, cell cycle inhibitor marker levels and mitochondrial health. IPF patients had altered peripheral blood immunophenotype including reduced B cells subsets, increased T cell subsets and increased granulocytes demonstrating disease-associated alterations in the immune system.ConclusionsOur results indicate that there are no differences in aMSC properties from IPF patients and HC, suggesting that autologous aMSCs may be an acceptable option for IPF therapy. The altered immune system of IPF patients may be a valuable biomarker for disease burden and monitoring therapeutic response,

Effect of intrabronchial administration of autologous adipose-derived mesenchymal stem cells on severe equine asthma

BackgroundSevere equine asthma (SEA) is a common chronic respiratory disease and a significant health and well-being problem in horses. Current therapeutic strategies improve pulmonary function and clinical signs in some horses, but in the long-term, return to full athletic function appears to be rare. The aim of this study was to assess the safety and the effect of intrabronchial administration of adipose-derived mesenchymal stem cells (AD-MSC) on pulmonary inflammatory and clinical parameters in horses with SEA.MethodsThis was a randomized controlled trial. Twenty adult horses diagnosed with SEA were randomly divided into two groups (n = 10), and treated either with a single intrabronchial application of autologous AD-MSC or oral dexamethasone for three weeks. A targeted clinical examination with determination of clinical score, maximal change in pleural pressure during the breathing cycle, and an endoscopic examination of the airways were performed at baseline and three weeks after treatment. Bronchoalveolar lavage fluid was analyzed cytologically, and IL-1β, IL-4, IL-8, IL-17, TNFα and IFNγ mRNA and protein concentrations were measured at baseline and three weeks. The horses were then monitored over one year for recurrence of SEA. A non-inferiority analysis and a linear mixed-effects model were performed to assess differences between treatments.ResultsThe non-inferiority of AD-MSC treatment was not established. However, AD-MSC administration significantly ameliorated the clinical score (P = 0.01), decreased the expression of IL-17 mRNA (P = 0.05) and IL-1β (P ≤ 0.001), IL-4 (P ≤ 0.001), TNFα (P = 0.02) protein levels, and had a positive long-term effect on SEA-associated clinical signs (P = 0.02).ConclusionsIntrabronchial administration of AD-MSC had limited short-term anti-inflammatory effects but improved the clinical signs of SEA at one year.

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.

Management of Meige's syndrome by facial and trigeminal nerve combing followed by transplantation of autologous adipose-derived mesenchymal stem cells

Increasing attention has recently been focused on reducing abnormal neuroexcitability in patients with Meige's syndrome using nerve combing surgery. However, nerve injury caused by nerve combing is of critical concern. Animal studies have shown that stem cells can repair cranial nerves; autologous adipose-derived mesenchymal stem cells have been proved to be safe and effective in clinical trials. A total of 38 patients with Meige's syndrome were enrolled in this prospective nonrandomized controlled study and divided into a non–stem cell group (n = 30) and a stem cell group (n = 8). Patients in the non-stem cell group underwent facial and trigeminal nerve combing only; patients in the stem cell group underwent adipose-derived mesenchymal stem cell implantation after facial and trigeminal nerve combing. A blepharospasm disability index score was used to evaluate effectiveness of the surgery, and a House–Brackmann grade was used to evaluate facial nerve injury. These data were recorded before the operation and at 7 days, 3 months, and 6 months after the operation. The overall improvement percentage of blepharospasm was 93% at 6-month follow-up in the non-stem cell group. A greater number of nerve combing events during the operation led to better outcomes but increased risk of facial paralysis. Patients in the stem cell group had better facial nerve function at the 6-month follow-up (House–Brackmann grade, P = 0.003) and better blepharospasm improvement at 3 and 6 months than those in the non–stem cell group (blepharospasm disability index score, P = 0.003 and P &lt; 0.001, respectively). Cerebrospinal fluid protein analysis showed that levels of several cytokines were significantly increased after adipose-derived mesenchymal stem cell transplantation, including interleukin-6 (P &lt; 0.01) and interferon gamma-induced protein 10 (P &lt; 0.0001) and the growth factors insulin-like growth factor-1 (P &lt; 0.0001), insulin-like growth factor-binding protein-1 (P &lt; 0.0001), growth/differentiation factor-15 (P &lt; 0.001), and angiopoietin-like 4 (P &lt; 0.001). Facial and trigeminal nerve combing combined with adipose-derived mesenchymal stem cell transplantation is a safe and effective remedy to improve recovery from Meige's syndrome.

Autologous adipose-derived mesenchymal stem cells and hydroxyapatite for bone defect inrabbits.

This study aims toevaluate the effect ofautologous adipose-derived mesenchymal stem cells (AAD-MSC), with and without synthetic absorbable hydroxyapatite (HAP-91), onthe bone regeneration inrabbits. Thirty-four female white New Zealand rabbits were submitted toa10mm distal diaphyseal radius ostectomy, divided into 3experimental groups according tothe treatment established. The bone gap was filled with 0.15ml ofa0.9% saline solution containing two million AAD-MSC (G1), orAAD-MSC associated with HAP-91 (G2). Thecontrol group (CG) received only 0.15ml ofthe 0.9% saline solution. Radiographs were made post-operatively, and after 15, 30, 45and 90days. Fifty percent ofthe samples were submitted toahistological examination at45days and theremaining ones at90days post-operatively. Radiographically, the periosteal reaction, bone callus volumeandbone bridge quality were superior inG2 (P<0.05). Histologically, the bone repair was faster and more efficient inG1at45days (P<0.05). Inconclusion, AAD-MSC improved the regeneration onthe experimentally induced bone defects inrabbits; however, the use ofhydroxyapatite requires caution given the granulomatous reaction produced inthe species.

Effectiveness of preconditioned adipose-derived mesenchymal stem cells with photobiomodulation for the treatment of diabetic foot ulcers: a systematic review.

The primary goal of this systematic review article was to provide an outline of the use of diabetic autologous adipose-derived mesenchymal stem cells (DAAD-MSCs) in the treatment of wounds and ulcers in animal models and patients with diabetes mellitus (DM). The secondary goal was to present the outcomes of pretreatment of diabetic adipose-derived mesenchymal stem cells (DAD-MSCs) with probable different agents in the treatment of diabetic foot ulcers (DFUs) and wounds. In view of possible clinical applications of AD-MSC-mediated cell therapy for DFUs, it is essential to evaluate the influence of DM on AD-MSC functions. Nevertheless, there are conflicting results about the effects of DAAD-MSCs on accelerating wound healing in animals and DM patients. Multistep research of the MEDLINE, PubMed, Embase, Clinicaltrials.gov, Scopus database, and Cochrane databases was conducted for abstracts and full-text scientific papers published between 2000 and 2020. Finally, 5 articles confirmed that the usage of allogeneic or autologous AD-MSCs had encouraging outcomes on diabetic wound healing. One study reported that DM changes AD-MSC function and therapeutic potential, and one article recommended that the pretreatment of diabetic allogeneic adipose-derived mesenchymal stem cells (DAlD-MSCs) was more effective in accelerating diabetic wound healing. Recently, much work has concentrated on evolving innovative healing tactics for hastening the repair of DFUs. While DM alters the intrinsic properties of AD-MSCs and impairs their function, one animal study showed that the pretreatment of DAlD-MSCs in vitro significantly increased the function of DAlD-MSCs compared with DAlD-MSCs without any treatment. Preconditioning diabetic AD-MSCs with pretreatment agents like photobiomodulation (PBM) significantly hastened healing in delayed-healing wounds. It is suggested that further animal and human studies be conducted in order to provide more documentation. Hopefully, these outcomes will help the use of DAAD-MSCs plus PBM as a routine treatment protocol for healing severe DFUs in DM patients.

Clinical outcomes following intra-articular injection of autologous adipose-derived mesenchymal stem cells for the treatment of osteoarthritis in dogs characterized by weight-bearing asymmetry.

AimsThis study investigates the effects of intra-articular injection of adipose-derived mesenchymal stem cells (AdMSCs) and platelet-rich plasma (PRP) on lameness, pain, and quality of life in osteoarthritic canine patients.MethodsWith informed owner consent, adipose tissue collected from adult dogs diagnosed with degenerative joint disease was enzymatically digested and cultured to passage 1. A small portion of cells (n = 4) surplus to clinical need were characterized using flow cytometry and tri-lineage differentiation. The impact and degree of osteoarthritis (OA) was assessed using the Liverpool Osteoarthritis in Dogs (LOAD) score, Modified Canine Osteoarthritis Staging Tool (mCOAST), kinetic gait analysis, and diagnostic imaging. Overall, 28 joints (25 dogs) were injected with autologous AdMSCs and PRP. The patients were followed up at two, four, eight, 12, and 24 weeks. Data were analyzed using two related-samples Wilcoxon signed-rank or Mann-Whitney U tests with statistical significance set at p < 0.05.ResultsAdMSCs demonstrated stem cell-like characteristics. LOAD scores were significantly lower at week 4 compared with preinjection (p = 0.021). The mCOAST improved significantly after three months (p = 0.001) and six months (p = 0.001). Asymmmetry indices decreased from four weeks post-injection and remained significantly lower at six months (p = 0.025).ConclusionThese improvements in quality of life, reduction in pain on examination, and improved symmetry in dogs injected with AdMSCs and PRP support the effectiveness of this combined treatment for symptom modification in canine OA for six months.Cite this article: Bone Joint Res 2021;10(10):650–658.

360 Genital Fat Transfer.

This study was designed to evaluate utility of transferring autologous adipose-derived mesenchymal stem cells with high regenerative capacity and adipose tissue derived-stromal vascular fraction, so-called 360 Vaginal Beautification technique, in labia majora augmentation and vaginal tightening operation. A total of 97 female patients who underwent labia majora augmentation and vaginal tightening operation with 360 Vaginal Beautification technique were included. Post-discharge early (3rd and 7th postoperative day) and late (1st and 3rd postoperative month) surgical complications were assessed , while the Female Genital Self-Image Scale (FGSIS) was applied before surgery and also during postoperative 6-12 months. All complications noted on postoperative 3rd day (ecchymosis of labia majus, ecchymosis of clitoral hood, tenderness in the pubic area and pain at the vaginal entrance points) regressed on postoperative 7th day with no infection, edema, lipoma or granuloma formation in any patient. Total mean FGSIS score was 17.7±1.6 in the pre-operative period, and increased significantly to 20.9±1.4 and 22.2±1.8 in the postoperative 6th month (p<0.001) and 12th month (p=0.013), respectively. The use of autologous fat, called 360 vaginal beautification, in the labia majora augmentation and vaginal tightening appears to be a safe technique due to use of autologous tissue transfer and to be associated with high satisfaction rate and an advantage of being more minimally invasive than surgical labia majora augmentation and vaginal tightening. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine Ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266 .

Can Autologous Adipose-Derived Mesenchymal Stem Cell Transplantation Improve Sexual Function in People with Sexual Functional Deficiency?

Sexual functional deficiency occurs at some point in life and becomes a problematic issue in middle-aged adulthood. Regenerative medicine, especially mesenchymal stem cell (MSC) transplantation, has developed extensively, with preclinical and clinical trials emphasizing the benefits of stem cell therapy for restoration of sexual deficiency. This study was designed to develop a new therapeutic stem cell treatment for people with sexual functional deficiency. Thirty-one patients, including 15 males and 16 females with a medical history of reduced sexual activity, met the inclusion criteria and were enrolled in the study, phase I/IIa clinical trial with a 12-month follow-up. Adipose tissue-derived mesenchymal stem/stromal cells (ADSC) were isolated by type I collagenase digestion and cultured at the Stem Cell Core Facility under ISO 14644-1. Each participant received 1 million cells/kg of body weight via the intravenous route. Safety was evaluated by assessing the occurrence of adverse events or severe adverse events. Efficacy was assessed in males by monitoring testosterone levels and administering the International Index of Erectile Function (IIEF) questionnaire and in females by monitoring anti-Mullerian hormone (AMH), estradiol (E2), and follicle-stimulatinghormone (FSH) levels and administering the Female Sexual Functioning Index (FSFI) questionnaire at baseline and 3-, 6-, and 12-months post-transplantation. There was no occurrence of severe adverse events after ADSC administration in our study. Post-transplantation sexual satisfaction was observed in all patients enrolled in this study. Testosterone levels in males increased soon after transplantation and were maintained at high levels for up to 6 months before decreasing again at the 12-month follow-up. No significant changes in AMH,FSH or E2 levels were recorded in female patients. Autologous ADSC infusion is a potential therapeutic option for patients with reduced sexual activity, especially for male patients. ClinicalTrials.gov. NCT03346967, Registered November 20, 2017.

Long-term survival of a patient with amyotrophic lateral sclerosis (ALS) who received autologous adipose-derived mesenchymal stem cells.

Amyotrophic lateral sclerosis (ALS) is a progressive debilitating neurodegenerative disease with a life expectancy of 3-5 years from initial symptoms. We report a case of ALS who received autologous adipose-derived mesenchymal stem cells (ADSC) and was followed up for 7 years. A 46-year-old man noticed weakness of his legs, difficulties on going down the stairs and coughing during eating in 2009. After complete workout, a diagnosis of ALS was confirmed. His ALS Functional Rating Scale-R (ALSFS-R) was 43. Symptoms rapidly progressed and he coughed and choked during eating. Starting in 2013, the patient received a total of six intravenous infusions of autologous ADSC. Changes in electromyogram, nerve conduction, and ALSFS-R were assessed. Soon after the administration, he noticed that he did not cough during conversation or eating food. Although he had difficulty in walking down the stairs, he remained well without coughing, dysarthria, or dysphagia. His ALSFS-R increased up to 45. Fascicular potentials were not detected in any muscles examined including trapezius muscle and rectus femoris muscles. The patient was well for 7 years after ADSC therapy by the time of this report and more than 10 years from the time of onset. The present case suggests that autologous ADSC can be administered safely and may be potentially useful in patients with ALS. Further investigations are warranted in order for the results to be generalized to other ALS patients.