Autologous Microfragmented Adipose Tissue Research Articles

The Healing and Aging-related Properties of Adipose Tissue Fragments Obtained through the Guided SEFFI Procedure’s Mechanical Fragmentation are Facilitated by the Exosomes Present in the Final Injection

The Injection of autologous Adipose-Derived Stem Cells (ADSCs) and Stromal Vascular Fraction (SVF) into dermal and subdermal layers can improve skin volume and rejuvenation. The SEFFI (Superficial Enhanced Fluid Fat Injection) technique, which involves minimal manipulation of autologous microfragmented adipose tissue, was utilized for harvesting and re-injection, using the SEFFILLER™ disposable medical device. Mechanical fragmentation of adipose tissue is a well-established surgical technique that stimulates tissue regeneration, filler, and biological activity. The study evaluated the biological properties (regenerative and anti-aging) of different harvest and processing fat graft methods among which the fragmented adipose tissue, specifically focusing on the presence of exosomes. Exosomes, nanometer-sized vesicles produced by cells for cellular communication, were found to contain miRNAs with anti-inflammatory, regenerative, and vascular content. The products’ contained exosomes were confirmed in the study through electron microscopy, Western Blotting, gene expression, and sequencing of miRNA content.

Autologous microfragmented adipose tissue treatment of knee osteoarthritis demonstrates effectiveness in 68% of patients at 4-year follow-up.

Adipose tissue-derived stem cells are an interesting therapeutic option for early knee osteoarthritis (OA) treatment due to their high plasticity, easiness of harvesting and rapidity of administration. The aim of this study was to evaluate the medium-term effectiveness and safety of Microfragmented Autologous Fat Tissue (MFAT) injection treatment at 4-year follow-up and to investigate potential correlations among patients' pre-treatment clinical condition and clinical outcomes to identify possible predicting factors for procedure success or failure. This is a prospective trial enrolling 46 patients with diagnosis of symptomatic knee OA and failure of previous conservative measures who underwent diagnostic arthroscopy and single autologous MFAT injection between June 2017 and July 2018. Patients were assessed with repeated clinical scoring systems at baseline, 6months, 1 and 4years after surgery. The evaluation included demographic characteristics, arthroscopic findings, and stem cell number from injected tissue. No major complications were reported during follow-up period and there was a significant increase of Lysholm knee score from baseline value of 61.7 ± 13.8 to 79.5 ± 16.9 at 4years (p < 0.001). The WOMAC score increased from a baseline value of 66.5 ± 14.7 to 82.8 ± 15.7 at 4years (p < 0.001) and there was a significant decrease of VAS pain score from baseline value of 6.3 ± 1.5 to 3.5 ± 2.6 at 4-year follow-up (p < 0.001). ROM improved significantly from 118.4 ± 2.6 to 122.5 ± 2.5 at 12months (p < 0.001), but did not improve at 4years (p > 0.05). 15 patients (32.6%) were considered treatment failures, because they required secondary surgery, further injection therapy or experienced symptoms persistence. Patient with synovitis had 75% failure rate, although synovitis did not result as a statistically significant factor influencing clinical outcome up to 4-year follow-up (p = 0.058). Age, cartilage defects severity, BMI, concomitant procedures, and stem cell number from injected MFAT did not show any significant correlation with the results. MFAT intra-articular injection is a safe procedure with positive improvements up to 4-year follow-up in patients with early knee OA. These findings suggest MFAT could be a minimally invasive treatment of early knee OA with durable benefits at mid-term evaluation. IRB number ID-3522.

ПРИМЕНЕНИЕ АУТОЛОГИЧНОЙ МИКРОФРАГМЕНТИРОВАННОЙ АДИПОЗНОЙ ТКАНИ В ЛЕЧЕНИИ ПОСТЛУЧЕВОГО ЯЗВЕННОГО ПРОКТИТА

Abstract. Introduction. Radiation-induced ulcerative proctitis is a serious complication of cancer radiotherapy for prostate, cervix, uterine body, anal canal, and other pelvic tumors. Given the development pattern, there are currently no pathogenetic methods for the treatment of radiation-induced ulcerative proctitis. Aim: To develop a technique for and evaluate its effectiveness in the treatment of patients with radiation-induced rectal ulcers using autologous microfragmented adipose tissue. Materials and Methods. The study included 30 patients, of which 24 (80.0%) were women and 6 (20.0%) were men. Manual lipoaspiration was used to obtain autologous adipose tissue. Then we performed its microfragmentation via transfers. Concentrated autologous adipose tissue was introduced into the edges of the radiation-induced ulcerative defect on the rectal wall under endoscopic control. При контрольной ректоскопии через 6 месяцев у 28 (93,3 %) пациентов была отмечена полная эпителизация постлучевых язвенных дефек- тов прямой кишки. Results and Discussion. The manipulation, from sampling the adipose tissue through the end of injection lasted a little more than an hour (Me = 75.0 min). No intraoperative complications were detected. In one female patient (3.3%), a local recurrence of cervical cancer was found, and therefore that patient was excluded from the study. Control rectoscopy showed the complete epithelialization of post-radiation ulcerative rectal defects in 28 (93.3%) patients after 6 months. Conclusions. The technique proposed to use autologous microfragmented adipose tissue is affordable and effective in the treatment of patients with radiation-induced ulcerative proctitis.

Autologous micro-fragmented adipose tissue in the treatment of atherosclerosis patients with knee osteoarthritis in geriatric population: A systematic review and meta-analysis.

Atherosclerosis and osteoarthritis are closely related. However, no high-quality studies have investigated the potential of micro-fragmented adipose tissue to treat patients with atherosclerosis accompanied by osteoarthritis. PubMed, Embase, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, WANFANG DATA, and CQVIP were searched for potentially eligible studies published before October 13, 2022. Due to the statistical limitations of the existing relevant literature, it is not possible to make direct statistics on the patients with osteoarthritis accompanied by atherosclerosis treated by micro-fragmented adipose tissue. The primary outcome consisted of two parts: 1) Correlation between atherosclerosis and osteoarthritis; 2) Scores of the Knee injury and Osteoarthritis Outcome Score (KOOS). And secondary outcomes were pain assessed by visual analog scale (VAS) or numeric rating scale (NRS), quality of life (QoL) (assessed using tools apart from the KOOS), and adverse events (AEs). Random meta-analysis was conducted using STATA 14.0. Nineteen studies were included. The metaanalysis evidenced a positive association between atherosclerosis and osteoarthritis (OR 1.17, CI 1.01-1.36). The mean absolute difference in KOOS subscale scores between pre- and post-treatment (mean with 95% confidence interval [CI]) was 19.65 (13.66, 25.63), 14.20 (4.64, 23.76), 19.95 (13.02, 26.89), 25.23 (14.80, 35.66), and 26.01 (13.68, 38.35) for pain, symptoms, activities of daily living (ADL), sports/recreation, and quality-of-life (QOL), respectively. The mean differences in VAS, resting VAS, activity VAS, and NRS between pre- and post-treatment was -8.24 (-10.66, -5.82), -3.61 (-4.49, -2.72), -4.17 (-4.89, -3.44), and -2.17 (-4.06, and -0.28), respectively. The mean difference in score of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), EQ-5D, and University of California in Los Angeles (UCLA) between pre- and post-treatment was -24.81 (-40.80, -8.82), 0.07 (0.02, 0.12), and 0.30 (-0.42, 1.02), respectively. The mean difference in Tegner score and the International Knee Documentation Committee (IKDC) score between pre- and post-treatment was 0.67 (-0.62, 1.97) and 13.70 (6.35, 21.04), respectively. The use of micro-fragmented adipose tissue was associated with risk of bruising, bleeding, hematoma, drainage, infection, soreness, swelling, pain, and stiffness in harvest and injection sites. Atherosclerosis and osteoarthritis share common risk factors and comorbidity. And the use of micro-fragmented adipose tissue may benefit for improving symptoms of knee osteoarthritis accompanied by atherosclerosis although may lead to some mild adverse events. Randomized controlled trials with long-term follow-up are necessary for further evaluation because many limitations of this meta-analysis cannot be ignored.

Efficacy and Long-Term Outcomes of Intra-Articular Autologous Micro-Fragmented Adipose Tissue in Individuals with Glenohumeral Osteoarthritis: A 36-Month Follow-Up Study.

Glenohumeral osteoarthritis (GOA) is associated with disabling shoulder pain that affects everyday life. Its management comprises various treatment approaches, both conservative and surgical. Regenerative medicine has gained a major role in the conservative treatment of osteoarthritis. Intra-articular injection of adipose-derived mesenchymal stem cells (ADMSCs) is a widely used regenerative medicine approach. The aim of this retrospective study was to report the safety and clinical outcomes of intra-articular injection of ADMSCs in patients with GOA over 36-months. This retrospective observational study involved patients with chronic shoulder pain resistant to standard conservative treatment and a diagnosis of concentric GOA, who received an intra-articular injection of autologous micro-fragmented adipose tissue (μFAT). The values of the Constant-Murley score (CMS), the visual analog scale (VAS), and the simple shoulder test (SST), collected at baseline and at 12, 24, and 36 months, were analyzed to assess treatment efficacy. The single assessment numeric evaluation (SANE) was used to rate patient satisfaction. The Friedman test was used to compare observations of CMS, VAS, and SST values repeated on the same subjects. The significance threshold was set at 0.05. The participants were 65 patients with a mean age of 54.19 years and a nearly equal gender distribution. Most had mild concentric GOA classified as Samilson-Prieto grade 1. The mean follow-up duration was 44.25 months. The postoperative clinical scores showed significant improvement. At 36 months, the CMS was 84.60, the VAS score was 3.34, and the SST score was 10.15 (all p < 0.0001). The SANE score at 36 months indicated that 54 patients (83.08%) were completely satisfied with the treatment. ADMSC treatment exerted favorable effects on the clinical outcomes of patients with GOA, providing pain relief and improving shoulder function. Our data support its use as a conservative treatment option for osteoarthritis.

Efficacy and Duration of Intra-Articular Autologous Micro-Fragmented Adipose Tissue in Athletes with Ankle Osteoarthritis: A 36-Month Follow-Up Study

Introduction: The intra-articular injection of autologous micro-fragmented adipose tissue (MAT) is increasingly used to manage pain and dysfunction in subjects with osteoarthritis (OA). The purpose of this retrospective study was to report the safety and clinical outcomes of intra-articular MAT in athletes with ankle OA. Methods: Participants were 21 symptomatic athletes aged 18–30 years suffering from mild-to-moderate ankle OA, who received 7 mL autologous MAT after failure of six-month conservative treatment. Clinical evaluation was performed before the procedure and at 6, 12, 24, and 36 months using the visual analog scale for pain, the American Orthopedic Foot and Ankle Society score and the Foot and Ankle Disability Index score. Patient satisfaction was assessed at 36 months. Results: The clinical scores documented a significant or marked improvement throughout the follow-up (p &lt; 0.05). However, at 36 months, they were significantly lower compared with the 24-month time point (p &lt; 0.05), although they were still significantly better than the baseline scores. There were no intraoperative or postoperative complications. Altogether, 81% of patients were very satisfied and 19% were satisfied. Conclusions: Intra-articular MAT injection appears to be a safe and effective treatment for ankle OA. In particular, it offers athletes wishing a fast return to their sports a new, minimally invasive therapeutic option.

Effects of Autologous Microfragmented Adipose Tissue on Healing of Tibial Plateau Levelling Osteotomies in Dogs: A Prospective Clinical Trial.

The aim of this study was to evaluate the effects of autologous microfragmented adipose tissue (MFAT) applied after mechanical fragmentation and assess these effects radiographically in bone healing in dogs subjected to tibial plateau levelling osteotomy (TPLO). Twenty dogs with unilateral cranial cruciate ligament disease were enrolled and randomly assigned to the treatment group (MFAT) or the control group (NT). The MFAT group underwent TPLO and autologous MFAT intra-articular administration, while the NT group underwent TPLO alone. Adipose tissue was collected from the thigh region, and MFAT was obtained by mechanical fragmentation at the end of the surgery. The patients were subjected to X-ray examination preoperatively, immediately postoperatively (T0), and at 4 (T1) and 8 (T2) weeks postoperatively. Two radiographic scores that had previously been described for the evaluation of bone healing after TPLO were used. A 12-point scoring system (from 0 = no healing to 12 = complete remodelling) was used at T0, T1, and T2, while a 5-point scoring system (from 0 = no healing to 4 = 76-100% of healing) was used at T1 and T2. The median healing scores were significantly higher at T1 and T2 for the MFAT group compared with the NT group for the 12-point (p < 0.05) and 5-point (p < 0.05) scoring systems. The intra-articular injection of autologous microfragmented adipose tissue can accelerate bone healing after TPLO without complications.

ПРИМЕНЕНИЕ АУТОЛОГИЧНОЙ МИКРОФРАГМЕНТИРОВАННОЙ АДИПОЗНОЙ ТКАНИ В ЛЕЧЕНИИ ПОСТЛУЧЕВОГО ЯЗВЕННОГО ПРОКТИТА

Introduction. Post-radiation ulcerative proctitis is a serious complication after radiotherapy for cancer of the prostate, cervix and uterine body, anal canal, and other pelvic tumors. Given the mechanism of occurrence, there are currently no pathogenetic methods for the treatment of post-radiation ulcerative proctitis. Aim. Is to develop a technique and evaluate its effectiveness in the treatment of patients with post-radiation rectal ulcers using autologous microfragmented adipose tissue. Material and methods. The study included 30 patients, of which 24 (80.0% were women and 6 (20.0%) were men. Manual lipoaspiration was used to obtain autologous adipose tissue. Then, microfragmentation was performed through transfers. The introduction of autologous concentrated adipose tissue was performed in edges of post-radiation ulcerative defect of the rectal wall under endoscopic control. Results and discussion. The duration of the manipulation from the moment of adipose tissue sampling to the end of the injection was a little more than an hour (Me = 75.0 min). No intraoperative complications were identified. One patient (3.3%) had a local recurrence of cervical cancer, and therefore the patient was excluded from the study. Control rectoscopy after 6 months in 28 (93.3%) patients showed complete epithelialization of post-radiation ulcerative defects of the rectum. Conclusion. The technique of using autologous microfragmented adipose tissue is affordable and effective in the treatment of patients with post-radiation ulcerative proctitis

Intra-Articular Injection of Autologous Micro-Fragmented Adipose Tissue for the Treatment of Knee Osteoarthritis: A Prospective Interventional Study.

To investigate the efficacy and safety of autologous micro-fragmented adipose tissue (MF-AT) for improving joint function and cartilage repair in patients with knee osteoarthritis. From March 2019 to December 2020, 20 subjects (40 knees) between 50 and 65 years old suffering from knee osteoarthritis were enrolled in the study and administered a single injection of autologous MF-A. The data of all patients were prospectively collected. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), knee society score (KSS), hospital for special surgery (HSS) score, visual analogue score (VAS) pain score, changes in cartilage Recht grade on magnetic resonance imaging (MRI) and adverse events were analyzed before and 3, 6, 9, 12 and 18 months after injection. The WOMAC, VAS, KSS and HSS scores at 3, 6, 9, 12 and 18 months after injection were improved compared with those before injection (p < 0.05). There was no significant difference in WOMAC scores between 9 and 12 months after injection (p > 0.05), but the WOMAC score 18 months after injection was worse than that at the last follow-up (p < 0.05). The VAS, KSS and HSS scores 9, 12 and 18 months after injection were worse than those at the last follow-up (p < 0.05). The Recht score improvement rate was 25%. No adverse events occurred during the follow-up. Autologous MF-AT improves knee function and relieves pain with no adverse events. However, the improved knee function was not sustained, with the best results occurring 9-12 months after injection and the cartilage regeneration remaining to be investigated.

Autologous micro-fragmented adipose tissue injection provides significant and prolonged clinical improvement in patients with knee osteoarthritis: a case-series study

PurposeAmong the conservative strategies to manage patients with symptomatic knee osteoarthritis (OA), an innovative approach exploiting the regenerative capability of adipose tissue and its resident MSCs (Mesenchymal Stem Cells or Medicinal Signalling Cells) has been proposed with encouraging results. This study aims to demonstrate the benefits of autologous micro-fragmented adipose tissue (MAT) injection in the conservative treatment of knee osteoarthritis and whether any variables may affect the outcome. This is a case series single-centre study in which patients underwent intraarticular MAT injection without any associated procedures.MethodsBased on inclusion and exclusion criteria, 49 patients (67 Knees) were included and retrospectively analysed with a mean follow-up of 34.04 ± 13.62 months (minimum 11 – maximum 59). Patients were assessed through the WOMAC and KOOS questionnaires at baseline (pre-treatment) and 1-, 3-, 6-, 12-, 24- and 36-month follow-up. A minimal clinically important difference (MCID) of at least 7.5 points for the WOMAC pain scale and 7.2 for the WOMAC function scale compared to the baseline value was used.ResultsWOMAC and KOOS scores improved after treatment compared to baseline at all follow-ups with p < 0.001. Male gender and Kellgren-Lawrence (KL) grade 2 were associated with smaller improvement in WOMAC and KOOS scores (with respect to females and to KL grade 1, respectively) up to 24 months. The percentage of patients who reach the MCID for WOMAC pain is generally lower than that of patients who reach the MCID for WOMAC function (around 80% at all time points), but it increases significantly over time. Moreover, the baseline score of the WOMAC pain and function influence the outcome. Patients with worse symptoms are more likely to reach the MCID.ConclusionsIntra-articular knee injection of MAT for the treatment of knee osteoarthritis (KOA), recalcitrant to traditional conservative treatments, proved to be effective in a high percentage of cases. The positive association between a worse pre-operative score and a better clinical response to the treatment would support the idea that intra-articular administration of MAT could be considered in patients with very symptomatic KOA in which joint-replacement surgeries are not indicated (or accepted).Level of EvidenceIV, case series.

Autologous micro-fragmented adipose tissue associated with arthroscopy in moderate–severe knee osteoarthritis: outcome at two year follow-up

BackgroundAdipose tissue has recently gained growing interest in the treatment of osteoarthritis (OA). The aim of the present study was to evaluate the efficacy of a single injection of autologous micro-fragmented adipose tissue (aMFAT) associated with arthroscopy (cartilage debridement/meniscal regularization or selective meniscectomy/micro-drilling) for symptomatic knee OA.MethodsThis retrospective, single-center study included 49 patients (50 knees) affected by knee OA (radiographic Kellgren-Lawrence III-IV) treated with a single injection of autologous micro-fragmented adipose tissue and knee arthroscopy. Knee Injury and Osteoarthritis Outcome Score (KOOS) and subjective International Knee Documentation Committee (IKDC) score were the primary outcome measures and were collected at one and 2 years post-operatively. Patients were divided into clusters based on age, complexity of arthroscopic procedures and chondral lesion grade.ResultsFour patients underwent knee replacement (8%). No major adverse events were reported. Minimal Clinically Important Difference (MCID) for KOOS and IKDC was reached by 84 and 74% of all cases at 1 year and by 80 and 76% at 2 years, respectively. High grade chondral lesions negatively affected the outcome at 2 years follow-up (p < 0.05 for IKDC, KOOS overall and 3 out of 5 subscales).ConclusionThe injection of micro-fragmented adipose tissue associated with arthroscopy demonstrated to be a safe and effective procedure for the treatment of knee OA, with a substantial improvement in IKDC and KOOS scores and without major complications.

Is intra-articular injection of autologous micro-fragmented adipose tissue effective in hip osteoarthritis? A three year follow-up

BackgroundRecently, increased attention on regenerative medicine and biological injective treatments have been proposed to restore native cartilage. Micro-fragmented adipose tissue (MFAT) has been studied for its anti-inflammatory, paracrine, and immunomodulatory effects. The long-term effects of MFAT are still poorly understood: the aim of the present study is to demonstrate how hip articular injections with autologous MFAT can have an impact on clinical outcomes.MethodsSeventy-one consecutive patients affected by early hip osteoarthritis underwent an ultrasound-guided hip injection of autologous MFAT between June 2017 and December 2018. Patients were divided into four groups according to the Oxford Hip Score. All patients received 4 mL of autologous micro-fragmented adipose tissue under an ultrasound guide. A clinical evaluation was done between 29 and 41 months after the initial treatment. During this follow-up period, we recorded any new treatment the patients had done, whether that be injection or arthroplasty surgery.ResultsThe study included 55 patients. Out of 55 patients, 28 saw benefits and were in no need of further treatment. Moreover, the score between the beginning and control increased by 6.9 points. Ten patients underwent a new articular injection: the mean time between the two injections was 635.7 ± 180 days. Seventeen patients underwent total hip replacement: the mean period between the autologous MFAT injection and the surgery was 495 days.ConclusionThis study found that intra-articular injections with autologous MFAT achieve beneficial clinical results in patients affected by early to moderate hip osteoarthritis, with an OHS between 48 and 30. Furthermore, these subjects are the ideal patients for whom this treatment obtains good clinical results.

Autologous microfragmented adipose tissue and leukocyte-poor platelet-rich plasma combined with hyaluronic acid show comparable clinical outcomes for symptomatic early knee osteoarthritis over a two-year follow-up period: a prospective randomized clinical trial

PurposeThe purpose of this prospective randomized clinical trial is to compare the clinical outcomes of three injections of leucocyte-poor platelet-rich plasma (LP-PRP) and hyaluronic acid (HA) to a single dose of autologous microfragmented adipose tissue (AMAT) in patients with mild osteoarthritis at a two-year follow-up.MethodsEighty symptomatic knees in fifty patients (mean age: 62.38 ± 11.88 years) with Kellgren-Lawrence grade 0 to 2 osteoarthritis were non blinded, randomly allocated into two equal groups. Group 1 consisted of 40 knees that received autologous LP-PRP + HA; Group 2 consisted of 40 knees treated with a single dose of AMAT injection. The outcomes were measured by Tegner, Marx, Visual Analogue Scale (VAS) for pain, International Knee Documentation Committee, and Knee Injury and Osteoarthritis Outcome Score (KOOS) at 6 (T1), 12 (T2), and 24 (T3) months. Adverse events were recorded at each follow-up timepoint. To assess score differences among subjects of the same gender and age, a subgroup analysis was performed.ResultsBoth groups had significant clinical and functional improvement at 6, 12, and 24 months (p < 0.05). Comparing the two groups, the AMAT groups showed significantly higher pre-operative Marx score (3.35 ± 4.91 vs. 1.78 ± 3.91) and VAS score (5.03 ± 2.02 vs. 3.85 ± 1.68) (p < 0.05), higher VAS (3.89 ± 2.51 vs. 2.64 ± 2.00) at T2 and KOOS-ADL (79.60 ± 20.20 vs. 65.68 ± 23.62), and lower KOOS-Sports (50.30 ± 30.15 vs. 68.35 ± 30.39) at T3 (p < 0.05). No patient from either group had experienced major adverse effects. In the LP-PRP group 12 (30%) patients presented swelling, redness, and mild pain for one day after injection and two patients had synovitis for two days and required paracetamol and local ice. In AMAT group 5 (12.5%) patients had ecchymosis and bruising at the fat aspiration site for three days.ConclusionAMAT did not show significant superior clinical improvement compared with three LP-PRP combined with HA injections in terms of functional improvement at different follow-up points. Both procedures were safe with no major complications reporting good results at mid-term follow-up, improving knee function, pain, and quality of live regardless of age and gender.Level of evidenceLevel I—Prospective Randomized Clinical Trial.

Effects of Intra-Articular Autologous Adipose Micrograft for the Treatment of Osteoarthritis in Dogs: A Prospective, Randomized, Controlled Study.

Simple SummaryOsteoarthritis (OA) is a very common musculoskeletal condition that affects dogs, as well as humans and other species, and causes pain, lameness, and disability. Since therapy is not always effective and is definitive only in some cases, OA is still a leading cause of euthanasia in dogs and a challenge for orthopedic surgeons. Recently, new therapeutic approaches, such as the use of autologous mesenchymal stem cells, have been developed. The purpose of this prospective, randomized, controlled, in vivo clinical study was to estimate the safety, feasibility, and efficacy of the intra-articular treatment of autologous microfragmented adipose tissue in dogs affected by spontaneous OA in comparison with a treatment with hyaluronic acid. Pain, lameness, the radiographic progression of OA, and synovial fluid inflammation were assessed. The results suggest that intra-articular injection of microfragmented autologous adipose tissue is safe, timesaving, cost-effective, minimally invasive, and can be easily done in one step. This treatment, compared with the hyaluronic acid treatment, showed better long-term pain control and an amelioration of synovial fluid quality, resulting in an improvement in joint function. This new treatment can be included among the effective therapies for OA. Additionally, the canine spontaneous OA model adopted in this study could play a key role in developing successful treatments for translational medicine.The purpose of this study was to estimate the safety, feasibility, and efficacy of the intra-articular treatment of autologous microfragmented adipose tissue in dogs with spontaneous osteoarthritis (OA) in comparison with hyaluronic acid (HA), the standard intra-articular treatment. Specifically, it clinically evaluated pain and lameness, the radiographic progression of osteoarthritis, and synovial fluid inflammation. This was a prospective, single-center, parallel-group, randomized, controlled, in vivo clinical study. Participants (n = 40) received either a single intra-articular injection of microfragmented adipose tissue or a single intra-articular injection of HA (1:1). Clinical outcomes were determined using a specialistic clinician assessment obtained by the completion of a specific clinical form based on the Vesseur modified lameness classification system, a pain evaluation using the Visual Analogue Scale (VAS), the measurement of the range of motion (ROM) of the affected joint, limb circumference, and the owners’ score evaluation using the Canine Brief Pain Inventory (CBPI) for up to 6 months after the time of injection. Patients underwent a radiographic examination to establish the degree of OA in the affected joint, and synovial fluid samples were collected to assess the biochemical environment of the joint and evaluate and quantify the cellular population and the presence of three specific inflammation biomarkers for up to 60 days. The results of this study suggest that microfragmented autologous adipose tissue is safe and can effectively relieve pain and improve function in dogs with spontaneous articular OA. This one-step procedure is simple, timesaving, cost-effective, minimally invasive, and eliminates the need for complex and time-intensive cell culture processing. Furthermore, the clinical evidence and cytological results suggest better long-term pain control, resulting in an improvement in joint function, compared to HA treatment. The canine spontaneous OA model could play a key role in developing successful treatments for human medicine.

Medicinal signaling cells niche in stromal vascular fraction from lipoaspirate and microfragmented counterpart

AimTo expand our previous findings by increasing the number of patients in a study characterizing medicinal signaling cells (MSC) of stromal vascular fraction from lipoaspirate (SVF-LA) and from microfragmented lipoaspirate (SVF-MLA) applied for the treatment of osteoarthritis (OA).MethodsTwenty OA patients, including 8 new patients, acquiring autologous microfragmented adipose tissue were enrolled. In-parallel immunophenotyping of SVF-LA and SVF-MLA was performed. The samples were incubated in a DuraClone SC prototype tube targeting the CD31, CD34, CD45, CD73, CD90, CD105, and CD146 surface markers, stained with the DRAQ7 cell nuclear dye and Live/Dead Yellow Fixable Stain, and analyzed by flow cytometry.ResultsThe population phenotypes in SVF-LA and SVF-MLA samples included CD31+CD34+CD73±CD90±CD105±CD146± endothelial progenitors (EP), CD31+CD34-CD73±CD90±CD105-CD146± mature endothelial cells, CD31-CD34-CD73±CD90+CD105-CD146+ pericytes, CD31-CD34+CD73±CD90+CD105-CD146+ transitional pericytes, and CD31-CD34+CD73highCD90+CD105-CD146- supra-adventitial-adipose stromal cells. Compared with the autologous SVF-LA samples, the prevailing cell type in SVF-MLA were EP, which outnumbered leukocytes and supra-adventitial-adipose stromal cells (SA-ASC). The ratio of progenitor cells in SVF-MLA samples differed between female and male patients, showing a higher EP-pericyte and pericyte-SA-ASC ratio in men.ConclusionOur results, hallmarked by EP-enriched anti-inflammatory features and indicating a possible sex-specific impact, contribute to defining the cellular composition of the clinically applied MSC serving as a regenerative cell therapy in OA.

Arthroscopic Rotator Cuff Repair Augmentation With Autologous Microfragmented Lipoaspirate Tissue Is Safe and Effectively Improves Short-term Clinical and Functional Results: A Prospective Randomized Controlled Trial With 24-Month Follow-up

Background: Autologous microfragmented lipoaspirate tissue has been recently introduced in orthopaedics as an easily available source of nonexpanded adipose-derived mesenchymal stem cells. Autologous microfragmented lipoaspirate tissue is expected to create a suitable microenvironment for tendon repair and regeneration. Rotator cuff tears show a high incidence of rerupture and represent an ideal target for nonexpanded mesenchymal stem cells. Purpose: To evaluate the safety and efficacy of autologous lipoaspirate tissue in arthroscopic rotator cuff repair. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: Consecutive patients referring to the investigation center for surgical treatment of magnetic resonance imaging–confirmed degenerative posterosuperior rotator cuff tears were assessed for eligibility. Those who were included were randomized to receive a single-row arthroscopic rotator cuff repair, followed by intraoperative injection of autologous microfragmented adipose tissue processed with an enzyme-free technology (treatment group) or not (control group). Clinical follow-up was conducted at 3, 6, 12, 18, and 24 months; at 18 months after surgery, magnetic resonance imaging of the operated shoulder was obtained to assess tendon integrity and rerupture rate. Results: An overall 177 patients were screened, and 44 (22 per group) completed the 24-month follow-up. A statistically significant difference in favor of the treatment group in terms of Constant-Murley score emerged at the primary endpoint at 6-month follow-up (mean ± SD; control group, 76.66 ± 10.77 points; treatment group, 82.78 ± 7.00 points; P = .0050). No significant differences in clinical outcome measures were encountered at any of the other follow-up points. No significant differences emerged between the groups in terms of rerupture rate, complication rate, and number of adverse events. Conclusion: This prospective randomized controlled trial demonstrated that the intraoperative injection of autologous microfragmented adipose tissue is safe and effective in improving short-term clinical and functional results after single-row arthroscopic rotator cuff repair. Registration: NCT02783352 (ClinicalTrials.gov identifier).

Autologous Microfragmented Adipose Tissue for the Treatment of Knee Osteoarthritis: Real-World Data at Two Years Follow-Up.

The purpose of the present study was to assess, prospectively, the safety, clinical effectiveness, and feasibility of a single intra-articular injection of microfragmented adipose tissue in different stages of knee osteoarthritis (OA). The study included patients (aged 18–70 years), affected by OA (Kellgren–Lawrence I-IV). Unselected patients were evaluated before and prospectively after 6, 12, and 24 months from the injection. Visual analog scale (VAS) and knee injury and osteoarthritis outcome score (KOOS) were used for clinical evaluations. A total of 202 patients were eligible. The mean follow-up time in the cohort of patients was 24.5 ± 9.6 months. Total KOOS significantly improved from pre-operative baseline levels to 6-month follow-up (p < 0.001), and again between 6- and 12-month follow-ups (p < 0.001). The VAS showed a prompt reduction at 6 months (p < 0.001 vs. baseline), but then it increased again at 12 months compared to the 6-month assessment (p < 0.001), even though it remained lower than baseline (p < 0.001). At 24 months, patients with KL-IV demonstrated a lower improvement compared to baseline; patients that had undergone previous corticosteroid injections had a greater risk to further injection treatment. The collected clinical results suggest that MFAT may represent a safe and effective treatment for OA symptoms, offering a low-demanding and minimally invasive treatment.

In Vitro Characterization of Canine Microfragmented Adipose Tissue Non-Enzymatically Extracted from the Thigh and Lumbar Regions.

Simple SummaryMesenchymal stem cells are located in bone marrow, adipose tissue, synovial membrane, and muscular tissue. They have an immunosuppressive, anti-inflammatory, and antifibrotic effect. Tissue engineering considers the usage of mesenchymal stem cells as a possible option for regenerating tissues, with respect to bone and cartilage, due to their ability to differentiate into multiple cytotypes (including chondrocytes and osteoblasts). Herein, we characterize a non-invasive solution based on Rigenera® technology, a mechanical disaggregation method able to produce autologous adipose tissue-derived micrografts which are analogous to adipose-derived stem cells.Within the adult canine population, disabilities and symptoms including joint pain and functional impairment are commonly observed in articular cartilage lesions and present a challenging feat in the operating room. Clinical settings require less invasive and more minimally manipulated measures facilitated by innovative and advanced technology. Mesenchymal stem cells have recently been proposed and, furthermore, autologous adipose tissue administration via injection has emerged as a new albeit somewhat controversial therapeutic tool. The purpose of this study is to characterize canine autologous micro-fragmented adipose tissue (micrografts) by mechanical approach without substantial manipulations. Adipose tissue samples collected from six dogs were processed by a Rigenera device and by enzymatic digestion from two different body regions (lumbar and thigh region). Interestingly, the immunophenotypic analysis attested that cells from Rigenera® were highly positive for the mesenchymal stem cells markers CD73 and CD90, less positive for hematopoietic CD45 and CD34, and negative for MHC class II antibodies (which play a role in immune responses). Finally, the Rigenera® technology obtained micrografts with a 35% higher expression of the IL10 gene with relevant anti-inflammatory activities compared to the enzymatic digestion protocol. This evidence suggests a potential improved clinical outcome capable of modulating inflammation and immune responses.

Platelets and Adipose Stroma Combined for the Treatment of the Arthritic Knee

Knee osteoarthritis (OA) leads to significant pain and disability, prompting new cell-based injections to lessen the symptoms. Biological therapies such as autologous microfragmented adipose tissue (AMAT) and a stromal vascular fraction (SVF) are a common source for harvesting mesenchymal and progenitor cells. Platelet-rich plasma (PRP) is associated with cytokines and growth factors. Recent studies have reported good clinical outcomes with AMAT, SVF, and PRP in knee osteoarthritis treatment. However, the preparation, processing, and application technique are vital to achieving satisfactory results. Many studies have examined outcomes after AMAT, SVF, or PRP injection, with encouraging results. Still, there is a lack of studies describing a technique that combines both methods, the timing, and the amount of SVF or PRP injected. This technical note’s objective was to describe a standardized new technique composed of platelet and adipose stroma to treat knee osteoarthritis (OA) and the processing method.

Stem Cells in Autologous Microfragmented Adipose Tissue: Current Perspectives in Osteoarthritis Disease.

Osteoarthritis (OA) is a chronic debilitating disorder causing pain and gradual degeneration of weight-bearing joints with detrimental effects on cartilage volume as well as cartilage damage, generating inflammation in the joint structure. The etiology of OA is multifactorial. Currently, therapies are mainly addressing the physical and occupational aspects of osteoarthritis using pharmacologic pain treatment and/or surgery to manage the symptomatology of the disease with no specific regard to disease progression or prevention. Herein, we highlight alternative therapeutics for OA specifically considering innovative and encouraging translational methods with the use of adipose mesenchymal stem cells.