Osteoarthritis (OA) is a degenerative joint disease that significantly impacts quality of life and poses a growing economic burden. Adipose tissue-derived therapies, including both cell-based and cell-free products, have shown promising potential in promoting cartilage repair, modulating inflammation, and improving joint function. Recent studies and clinical trials have demonstrated their regenerative effects, highlighting their feasibility as a novel treatment approach for OA. This review summarises the therapeutic mechanisms and latest advancements in adipose tissue-derived therapies, providing insights into their clinical applications and future prospects.

Background/Objectives: Treatment of knee osteoarthritis (OA) with autologous stem cells from microfragmented adipose tissue (MFAT) has shown promising but varying results. Multiple stem cell types, including CD34+, CD146+, and CD271+ stem cells, have been identified within MFAT. Patient-specific heterogeneity in stem cell populations and the content of highly potent cells may be determining factors for a successful treatment outcome. The current study aimed to identify the most promising stem cell type in MFAT to treat OA, focusing on their chondrogenic and osteogenic differentiation performance. Methods: CD34+, CD146+, and CD271+ stem cells from the MFAT of eight patients with knee OA were separated using magnetic-activated cell sorting (MACS) and analyzed as subtypes. Unsorted cells were used as a control. Chondrogenic and osteogenic in vitro differentiation were assessed through Safranin-O and H&E staining, pellet size, and qPCR for chondrogenesis, as well as Alizarin Red S staining and qPCR for osteogenesis. Results: CD34+, CD146+, and CD271+ stem cells were doubled using MACS. All subtypes were able to undergo osteogenic differentiation with Alizarin Red S staining, revealing a significant increase in calcium deposits of induced cells compared to non-induced controls. CD146+ stem cells showed higher calcium deposition compared to CD34+, CD271+, and unsorted stem cells. All cell types could form chondrogenic pellets. CD271+ stem cells produced more proteoglycans, as shown by Safranin-O staining, than CD34+ and CD146+ stem cells, but not more than the unsorted stem cells. After differentiation induction, all cell types showed an upregulation of most chondrogenic and osteogenic biomarkers. Conclusions: CD146+ stem cells showed the highest osteogenic differentiation performance for calcium deposition, while CD271+ stem cells showed the greatest chondrogenic differentiation performance for proteoglycan formation. The prevalence of these stem cell types may play a critical role in the clinical effectiveness when treating OA.

To evaluate the effectiveness of microfragmented adipose tissue (MFAT) for pain relief and improved joint functionality in osteoarthritis (OA) of the knee in a randomized controlled clinical trial with 1-year follow-up.

Seventy-five patients were stratified by baseline pain level and randomized to 1 of 3 treatment groups: MFAT, corticosteroid (CS), or saline control (C) injection. Patients 18 years of age or older, diagnosed with symptomatic OA of the knee, with radiographic evidence of OA of the knee and a visual analog pain scale score of 3 of 10 or greater were included. Patients were excluded if they had any previous intra-articular knee injection, current knee ligamentous instability, or an allergy to lidocaine/corticosteroid. The visual analog pain scale, Western Ontario and McMaster Universities Osteoarthritis Index, and the Knee Injury and Osteoarthritis Outcome score (KOOS) were recorded preprocedure and at 2 weeks, 6 weeks, 3 and 6 months, and 1-year follow-up.

MFAT demonstrated consistent and statistically significant improvements across all primary outcome measures for joint pain and functionality compared with C. For MFAT, there was a significant improvement over baseline at each follow-up, with median (95% confidence interval) KOOS Pain score changes of 18.1 (11.1-26.4) at week 2 to 27.8 (19.4-37.5) at 1 year. For CS, the median KOOS pain score reached a maximum of 22.2 (15.3-30.6) at week 2, only to level off to 13.9 (-2.8 to 29.2), a level not statistically different from baseline, at 1 year. The median changes for C hovered around 6 to 11 points, with statistically significant improvements over baseline indicating a placebo effect. Similar trends were seen for the Western Ontario and McMaster Universities Osteoarthritis Index Pain score and VAS Pain score.

In this study, MFAT demonstrated a clinically significant improvement in primary outcome scores compared with the C group, whereas the CS group only showed statistically significant improvement compared with the C group at 2 and 6 weeks. This finding indicates that MFAT may be a viable alternative treatment for patients with OA of the knee who fall into the orthopaedic treatment gap.

Level II, partially blinded, randomized controlled clinical trial.

To perform a systematic review of clinical outcomes in patients who underwent treatment with micro-fragmented aspirated tissue for symptoms of knee osteoarthritis.

Medline, Embase, Scopus, and Google Scholar were screened for studies from 2000 to 2023. Risk of bias (ROB) was assessed using the Cochrane Collaboration's tools and the Risk Of Bias In Non-randomised Studies-of Interventions tool. Study quality was assessed with the modified Coleman Methodology Score and Methodological Index for Non-Randomized Studies score. Heterogeneity was assessed using χ2 and I2 statistics.

Twenty-one studies were included. One study had a high ROB, 1 had a critical ROB, 3 had serious ROB, and 16 had a moderate ROB. The mean Coleman score was 58, demonstrating fair study quality; the Methodological Index for Non-Randomized Studies score had a mean value of 13, indicating overall fair quality. Best evidence synthesis revealed moderate evidence. The visual analog scale score improved from 5.2 to 3.2 at 6 and 12 months. Knee injury and Osteoarthritis Outcome Score (KOOS) activities of daily living subscore improved from 58.8 to 70.2 at 6 months and 67.5 at 12 months. KOOS pain subscore improved from 54.3 to 70.2 at 6 months and 72.4 at 12 months. KOOS quality of life subscore improved from 33.1 to 43.6 at 6 months and 42.9 at 12 months. KOOS sports subscore improved from 23.7 to 43.6 at 6 months and 57.4 at 12 months. KOOS symptoms subscore improved from 55.3 to 70.1 at 6 months and 67.9 at 12 months. The Western Ontario and McMaster Universities Osteoarthritis Index score steadily increased from 61.8 at baseline to 78.4 at 12 months.

micro-fragmented aspirated tissue injection therapy for the treatment of symptomatic knee osteoarthritis is effective and improves pain and functional outcomes. Moderate study quality combined with a moderate risk of bias, moderate certainty of evidence, and moderate best synthesis evidence reduces external validity. Therefore, the results should be interpreted with a degree of caution.

Level IV, systematic review of Level I-IV studies.

Avascular necrosis (AVN) is characterized by compromised blood supply to bone tissue, often resulting in significant pain and functional impairment. Conservative treatment options for early-stage AVN of the talus are scarce, with non-weight-bearing protocols and hyperbaric oxygen therapy showing limited efficacy. This report presents a potential novel approach to managing non-traumatic AVN of the talus using a combination of adipose-derived stromal vascular fraction (SVF) and platelet-rich plasma (PRP). A 60-year-old male presented with progressive right ankle pain of a two-year evolution. Magnetic resonance imaging (MRI) revealed stage II AVN of the talus with extensive bone infarctions occupying almost all of its volume but with no collapse. A single injection of SVF and PRP was performed after diagnostic arthroscopy, followed by a tailored rehabilitation protocol. The patient experienced significant pain relief, with no further need for analgesics, and was able to return to non-impact sports. At the 18-month follow-up, functional scores showed significant improvement, and MRI showed stable AVN with no evidence of collapse. This report highlights SVF and PRP as a potential effective conservative option for non-traumatic talar AVN.

Orthobiologics has seen a renaissance over the last decade as an adjunct therapy during osteotomy due to the limited inherent regenerative potential of damaged intraarticular tissues.

This systematic review aims to present the latest evidence regarding using orthobiologics with simultaneous high tibial osteotomy (HTO) for knee osteoarthritis. The results of this study may guide surgeons to improve their clinical results and clear the air regarding confusion over whether or not to add orthobiologics to HTO in clinical practice backed by scientific evidence.

According to PRISMA guidelines a systematic search for relevant literature was performed in the PubMed (MEDLINE), Scopus, EMBASE, and Cochrane Library databases of all studies published in English from January 1990 to May 2023. The following search terms were entered into the title, abstract, and keyword fields: "knee" or "osteotomy" AND "valgus" or "varus" AND "regenerative medicine" or "PRP" or "mesenchymal stem cells" or "stem cells" or "BMAC" or "bone marrow" or "growth factors" or "umbilical cord blood-derived mesenchymal stem cell" or "stromal vascular fraction". The AMSTAR-2 checklist was used to confirm the quality of the systematic review. Randomised controlled trials (RCTs), prospective and retrospective comparative cohort studies, case-control studies, and case series were included. Studies that reported clinical outcomes in patients treated with knee osteotomy for varus/valgus knee with concomitant adjunction of regenerative treatment [Platelet-rich plasma (PRP), Adipose-derived stem cells (ADSC), Human Umbilical Cord Blood-Derived (HUCBD), Mesenchymal Stem Cells (MSC), bone marrow aspirate concentrate (BMAC), stromal vascular fraction (SVF)] were included. The outcome measures extracted from the studies were the KOOS score, Lysholm score, Subjective IKDC, WOMAC Score, KSS, Tegner, HSS, radiographic tibiofemoral angle, posterior tibial slope and complications. The current systematic review is registered in the PROSPERO Registry (CRD42023439379).

Osteotomy for unicompartmental arthritis with adjunction of orthobiologics such as PRP, ADSC, HVCBD, MSC, BMAC, and SVF presents a consistent statistically significant clinical improvement compared to preoperative scores regardless of the treatment modality used and there were no notable complications associated with the use of these novel agents.

Orthobiologics and knee osteotomies could improve outcomes in patients with knee osteoarthritis desiring Knee preservation surgeries. However, only a few studies are available on the topic to conclude anything with certainty, the patients included in the studies could not be disintegrated based on the grade of osteoarthritis (OA), type, dosage and frequency of administration of orthobiologic and type of additional surgical procedures used. Therefore, better-structured RCTs are required to implement this finding into routine Orthopaedic practice.

Level 4.

Osteoarthritis (OA) is a progressive joint disease, and over 240 million people suffer from symptomatic OA, primarily in the knee, and mainly affects the elderly population over 65. A combination of different risk factors leads to biological changes in the microenvironments of the joints, causing cartilage overload and chondrocyte aging. Adipose-derived MSCs (ADSCs) are demonstrated to improve joint environments with an effective therapy for Knee OA. This review focused on patients over 65 years old to evaluate the effectiveness of ADSC therapies in treating KOA in elderly patients and demonstrate that complications are not higher in this cohort of patients.

We conducted a bibliography search through the PubMed, Scopus, and Cochrane databases for English-language and human clinical trials published until Feb 7, 2024. We extracted the following study characteristics: Authors, year of publication, type of study, number of patients, number of knees, sex, Kellgren-Lawrence classification, culture ADSC, Number of cells injected, mean follow-up, adverse events, significant complications, and clinical outcomes data were extracted recorded and analyzed.

According to inclusion criteria, seven clinical trials on autologous adipose-derived stem cells were considered. Four studies analyzed stem cells as a stromal vascular fraction (SVF), two as ADSC cultured, and 1 study investigated the MAT procedure. All studies reported improved clinical outcomes using autologous adipose-derived stem cells, on 339 knees. Post-treatment increased KOOS, WOMAC, IKS, VAS, and Lysholm knee scores were highlighted. All studies showed an improvement in all outcomes scores, and regarding complications, only 44 knees underwent adverse events, but no significant complications were found in all the studies reported.

The current systematic review demonstrated that using autologous adipose-derived stem cells improved clinical outcomes and is effective and safe in elderly patients. Additionally, this study will encourage orthopedic surgeons not to consider surgery as the only solution in elderly patients who are refractory to treatment and do not show end-stage knee osteoarthritis.

Level IV, systematic review of level IV studies.

In this editorial, we comment on the paper by Muthu et al published in the recent issue of the journal. This editorial review focusses on the use of adipose-derived stem cells (ADSCs) in knee osteoarthritis treatment. We discuss the differences between the stromal vascular fraction and microfragmented adipose tissue and highlight the results of clinical studies comparing both treatments and the use of hyaluronic acid, platelet-rich plasma, and bone marrow aspirate concentrate. The use of expanded ADSCs is also discussed; moreover, concerns regarding treatment with ADSCs, particularly the heterogeneity of published studies and the need to standardize protocols to explore clinical potential is explored.

The association of adipose tissue-derived injectable products with platelet-rich plasma (PRP) has been promoted for osteoarthritis (OA) treatment. The aim of this study was to investigate the preclinical and clinical evidence supporting the potential of this combined approach to treat OA.

A systematic review was performed in January 2024 on five databases (PubMed, Embase, Scopus, Cochrane, and Web-of-Science) to identify preclinical in vivo and clinical studies. Safety, OA biomarker changes, and outcomes in terms of clinical and imaging results were analyzed. The quality of studies was assessed with the SYRCLE's tool for preclinical studies and the Downs and Black checklist for clinical studies.

Ten preclinical studies (223 animals) and 14 clinical studies (594 patients) were included. Preclinical results documented improvements at the cartilage histological and immunohistochemical evaluation and at the biomarkers level. Clinical studies confirmed the procedure's safety, and the case series suggested satisfactory results in different joints in terms of symptoms and function improvement, with positive findings at the biomarker level. However, the randomized controlled trials did not document any clinical benefit, nor any changes in the imaging analysis. A large heterogeneity and overall poor quality were documented in both preclinical and clinical studies.

There is an increasing interest in the use of adipose tissue-derived injectable products associated with PRP for the treatment of OA joints, with preclinical studies showing promising results with this combined approach. However, clinical studies did not confirm the benefits offered by PRP augmentation to adipose tissue-derived injectable products in patients affected by OA.

The aim of this study was to review the current literature regarding the effects of intra-articularly applied, fat-derived orthobiologics (FDO) in the treatment of primary knee osteoarthritis over a mid-term follow-up period. A systematic literature search was conducted on the online databases of Scopus, PubMed, Ovid MEDLINE, and Cochrane Library. Studies investigating intra-articularly applied FDO with a minimum number of 10 knee osteoarthritis patients, a follow-up period of at least 2 years, and at least 1 reported functional parameter (pain level or Patient-Reported Outcome Measures) were included. Exclusion criteria encompassed focal chondral defects and techniques including additional arthroscopic bone marrow stimulation. In 28 of 29 studies, FDO showed a subjective improvement in symptoms (pain and Patient-Reported Outcome Measures) up to a maximum follow-up of 7.2 years. Radiographic cartilage regeneration up to 3 years postoperatively, as well as macroscopic cartilage regeneration investigated via second-look arthroscopy, may corroborate the favorable clinical findings in patients with knee osteoarthritis. The methodological heterogeneity in FDO treatments leads to variations in cell composition and represents a limitation in the current state of knowledge. However, this systematic review suggests that FDO injection leads to beneficial mid-term results including symptom reduction and preservation of the affected joint in knee osteoarthritis patients.

Pain is the major symptom of osteoarthritis (OA) and is an important factor in strategies to manage this disease. However, the current standard of care does not provide satisfactory pain relief for many patients. The pathophysiology of OA is complex, and its presentation as a clinical syndrome is associated with the pathologies of multiple joint tissues. Treatment options are generally classified as pharmacologic, nonpharmacologic, surgical, and complementary and/or alternative, typically used in combination to achieve optimal results. The goals of treatment are the alleviation of symptoms and improvement in functional status. Several studies are exploring various directions for OA pain management, including tissue regeneration techniques, personalized medicine, and targeted drug therapies. The aim of the present narrative review is to extensively describe all the treatments available in the current practice, further describing the most important innovative therapies. Advancements in understanding the molecular and genetic aspects of osteoarthritis may lead to more effective and tailored treatment approaches in the future.

Osteoarthritis (OA) is the most prevalent form of degenerative whole-joint disease. Before the final option of knee replacement, arthroscopic surgery was the most widely used joint-preserving surgical treatment. Emerging regenerative therapies, such as those involving platelet-rich plasma, mesenchymal stem cells, and microfragmented adipose tissue (MFAT), have been pushed to the forefront of treatment to prevent the progression of OA. Currently, MFAT has been successfully applied to treat different types of orthopedic diseases.

To assess the efficacy and safety of MFAT with arthroscopic surgery in patients with knee OA (KOA).

A randomized, multicenter study was conducted between June 2017 and November 2022 in 10 hospitals in Zhejiang, China. Overall, 302 patients diagnosed with KOA (Kellgren-Lawrence grades 2-3) were randomized to the MFAT group (n = 151, were administered MFAT following arthroscopic surgery), or the control group (n = 151, were administered hyaluronic acid following arthroscopic surgery). The study outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, the visual analog scale (VAS) score, the Lequesne index score, the Whole-Organ Magnetic Resonance Imaging Score (WORMS), and safety over a 24-mo period from baseline.

The changes in the WOMAC score (including the three subscale scores), VAS pain score, and Lequesne index score at the 24-mo mark were significantly different in the MFAT and control groups, as well as when comparing values at the posttreatment visit and those at baseline (P < 0.001). The MFAT group consistently demonstrated significant decreases in the WOMAC pain scores and VAS scores at all follow-ups compared to the control group (P < 0.05). Furthermore, the WOMAC stiffness score, WOMAC function score, and Lequesne index score differed significantly between the groups at 12 and 24 mo (P < 0.05). However, no significant between-group differences were observed in the WORMS at 24 mo (P = 0.367). No serious adverse events occurred in both groups.

The MFAT injection combined with arthroscopic surgery treatment group showed better mid-term clinical outcomes compared to the control group, suggesting its efficacy as a therapeutic approach for patients with KOA.

The use of minimally manipulated adipose tissue (MM-AT) products is gaining increasing interest for the treatment of knee osteoarthritis (OA). MM-AT represents an easy way to exploit adipose tissue properties, although clinical evidence is still limited, as well as their benefits with respect to more documented orthobiologics like platelet-rich plasma (PRP). A systematic review and meta-analysis were performed to evaluate the safety and efficacy of MM-AT products for knee OA management. The risk of bias of the included studies was evaluated using the Dawns and Black checklist for all the included studies and RoB-2.0 for randomized controlled trials (RCTs). Thirty-three clinical studies were included in the qualitative analysis: 13 prospective case series, 10 retrospective case series, 7 RCTs, 2 retrospective comparative studies, and 1 prospective comparative study. An overall clinical improvement and few minor adverse events were observed. Five RCTs comparing MM-AT and PRP injections were meta-analyzed, showing comparable results. The analysis also highlighted the limits of the literature, with only a few high-level trials and an overall low quality. Even though the current literature is still limited, the available evidence suggests the safety and overall positive results of the intra-articular injections of MM-AT products for knee OA treatment.

Osteoarthritis, predominantly of the knee, is a highly prevalent disease leading to pain, reduced quality of life, and significantly reduced ability to work. With autologous orthobiologic options, new regenerative treatment methods have emerged, offering an alternative to early surgical intervention. Supercharged Liparthroplasty combines arthroscopy with lipoaspirate and plasma infiltration of the joint. Lipoaspirate contains high levels of adipose-derived stem cells, which show chondroprotective and anti-inflammatory qualities. Intra-articular injection, combined with platelet-rich plasma administration for accelerated cartilage metabolism, thus provides an optional approach in osteoarthritis treatment. This article aims to provide in detail our regimen for Supercharged Liparthroplasty, including tissue harvesting and preparation of the injectables, therefore enabling physicians to adopt this point-of-care technique.

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.

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.

The biological enhancement of tissue regeneration and healing is an appealing perspective in orthopedics. We aimed to conduct a systematic review to describe the global distribution of studies investigating the use of adipose tissue derivates in orthopedics and to provide information on their quality and on the products available. The quality of the included studies was assessed using the modified Coleman Methodology Score (mCMS) and the Cochrane risk-of-bias tool for randomized trials. Eighty-two studies were included, with a total of 3594 patients treated. In total, 70% of the studies investigated the treatment of knee disorders, predominantly osteoarthritis; 26% of all studies dealt with expanded adipose-derived stem/stromal cells (ADSCs), 72% of which had stromal vascular fraction (SVF); 70% described the injection of adipose tissue derivates into the affected site; and 24% described arthroscopies with the addition of adipose tissue derivates. The mean mCMS for all studies was 51.7 ± 21.4 points, with a significantly higher score for the studies dealing with expanded ADSCs compared to those dealing with SVF (p = 0.0027). Our analysis shows high heterogeneity in terms of the types of performed procedures as well as the choice and processing of adipose tissue derivates.

To investigate if viable stem cells could be isolated and expanded from cryopreserved microfragmented adipose tissue (AT) harvested from patients with knee osteoarthritis.

Microfragmented abdominal AT from knee osteoarthritis patients was cryopreserved at -80 °C in cryoprotectant-medium. The samples were thawed for stem cell isolation by tissue explant culture (TEC) and enzymatic digestion (ED), respectively. Viability, population doublings, and doubling time were assessed by trypan blue staining and flow cytometry. Cell type and senescence-associated β-galactosidase activity were analyzed by flow cytometry. Osteogenic and adipogenic differentiation was assessed quantitatively by Alizarin-Red-S and Oil-Red-O staining, respectively.

Microfragmented AT from 7 patients was cryopreserved for a period of 46-150 days (mean (SD) 115.9 days (44.3 days)). Viable stem cells were successfully recovered and expanded from all patients using both isolation methods with no significant difference in viable population doublings or doubling time from passage 1 to 3 (p > 0.05). Low levels of senescence-associated β-galactosidase activity was detected for both methods with no significant difference between TEC and ED (p = 0.17). Stemness was verified by stem cell surface markers and osteogenic and adipogenic differentiation performance. Adventitial stem cells (CD31^-CD34⁺CD45^-CD90⁺CD146^-), pericytes (CD31^-CD34^-CD45^-CD90⁺CD146⁺), transitional pericytes (CD31^-CD34⁺CD45^-CD90⁺CD146⁺), and CD271⁺ stem cells (CD31^-CD45^-CD90⁺CD271⁺) were identified using both methods. More pericytes were present when using TEC (25% (24%)) compared to ED (3% (2%)) at passage 4 (p = 0.04).

Viable stem cells can be isolated and expanded from cryopreserved microfragmented AT using both TEC and ED. TEC provides more clinically relevant pericytes than ED.

This study evaluated outcomes in patients with knee osteoarthritis following stromal vascular fraction implantation and assessed the associated prognostic factors.

We retrospectively evaluated 43 patients who underwent follow-up magnetic resonance imaging 12 months after stromal vascular fraction implantation for knee osteoarthritis. Pain was assessed using the visual analogue scale and measured at baseline and 1-, 3-, 6-, and 12-month follow-up appointments. In addition, cartilage repair was evaluated based on the Magnetic Resonance Observation of Cartilage Repair Tissue scoring system using the magnetic resonance imaging from the 12-month follow-up. Finally, we evaluated the effects of various factors on outcomes following stromal vascular fraction implantation.

Compared to the baseline value, the mean visual analogue scale score significantly and progressively decreased until 12 months post-treatment (P < 0.05 for all, except n.s. between the 1 and 3-month follow-ups). The mean Magnetic Resonance Observation of Cartilage Repair Tissue score was 70.5 ± 11.1. Furthermore, the mean visual analogue scale and Magnetic Resonance Observation of Cartilage Repair Tissue scores significantly correlated 12 months postoperatively (P = 0.002). Additionally, the cartilage lesion size and the number of stromal vascular fraction cells significantly correlated with the 12-month visual analogue scale scores and the Magnetic Resonance Observation of Cartilage Repair Tissue score. Multivariate analyses determined that the cartilage lesion size and the number of stromal vascular fraction cells had a high prognostic significance for unsatisfactory outcomes.

Stromal vascular fraction implantation improved pain and cartilage regeneration for patients with knee osteoarthritis. The cartilage lesion size and the number of stromal vascular fraction cells significantly influenced the postoperative outcomes. Thus, these findings may serve as a basis for preoperative surgical decisions.

IV.

Cell-based therapies using lipoaspirate are gaining popularity in orthopaedics due to their hypothesised regenerative potential. Several 'point-of-care' lipoaspirate-processing devices/systems have become available to isolate cells for therapeutic use, with published evidence reporting their clinical relevance. However, few studies have analysed the composition of their 'minimally-manipulated' cellular products in parallel, information that is vital to understand the mechanisms by which these therapies may be efficacious. This scoping review aimed to identify devices/systems using mechanical-only processing of lipoaspirate, the constituents of their cell-based therapies and where available, clinical outcomes.

PRISMA extension for scoping reviews guidelines were followed. MEDLINE, Embase and PubMed databases were systematically searched to identify relevant articles until 21st April 2022. Information relating to cellular composition and clinical outcomes for devices/systems was extracted. Further information was also obtained by individually searching the devices/systems in the PubMed database, Google search engine and contacting manufacturers.

2895 studies were screened and a total of 15 articles (11 = Level 5 evidence) fulfilled the inclusion criteria. 13 unique devices/systems were identified from included studies. All the studies reported cell concentration (cell number regardless of phenotype per millilitre of lipoaspirate) for their devices/systems (range 0.005-21 × 106). Ten reported cell viability (the measure of live cells- range 60-98%), 11 performed immuno-phenotypic analysis of the cell-subtypes and four investigated clinical outcomes of their cellular products. Only two studies reported all four of these parameters.

When focussing on cell concentration, cell viability and MSC immuno-phenotypic analysis alone, the most effective manual devices/systems were ones using filtration and cutting/mincing. However, it was unclear whether high performance in these categories would translate to improved clinical outcomes. Due to the lack of standardisation and heterogeneity of the data, it was also not possible to draw any reliable conclusions and determine the role of these devices/systems in clinical practice at present.

Level V Therapeutic.