The Effect of Intra-articular Injection of Autologous Microfragmented Fat Tissue on Proteoglycan Synthesis in Patients with Knee Osteoarthritis Adipose Mesenchymal Stromal Cell-Based Therapy for Severe Osteoarthritis of the Knee: A Phase I Dose-Escalation Trial. Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial. The microfracture technique for the treatment of articular cartilage lesions in the knee. A prospective cohort study. Adipose Derived Stromal Cell (ADSC) Injections for Pain Management of Osteoarthritis in the Human Knee Joint. Matrix-induced autologous chondrocyte implantation versus microfracture in the treatment of cartilage defects of the knee: a 2-year randomised study Human adipose-derived mesenchymal stem cells for osteoarthritis: a pilot study with long-term follow-up and repeated injections.
Osteoarthritis ( OA ) is one of the leading musculoskeletal disorders in the adult population . It is associated with cartilage damage triggered by the deterioration of the extracellular matrix tissue . The present study explores the effect of intra-articular injection of autologous microfragmented adipose tissue to host chondrocytes and cartilage proteoglycans in patients with knee OA . A prospect i ve , non-r and omized , interventional , single-center , open-label clinical trial was conducted from January 2016 to April 2017 . A total of 17 patients were enrolled in the study , and 32 knees with osteoarthritis were assessed .  Surgical intervention ( lipoaspiration ) followed by tissue processing and intra-articular injection of the final microfragmented adipose tissue product into the affected knee(s ) was performed in all patients . Patients were assessed for visual analogue scale ( VAS ) , delayed gadolinium-enhanced magnetic resonance imaging of cartilage ( dGEMRIC ) and immunoglobulin G ( IgG ) glycans at the baseline , three , six and 12 months after the treatment . Magnetic resonance sequence in dGEMRIC due to infiltration of the anionic , negatively charged contrast gadopentetate dimeglumine ( Gd-DTPA2− ) into the cartilage indicated that the contents of cartilage glycosaminoglycans significantly increased in specific areas of the treated knee joint . In addition , dGEMRIC consequently reflected subsequent changes in the mechanical axis of the lower extremities . The results of our study indicate that the use of autologous and microfragmented adipose tissue in patients with knee OA ( measured by dGEMRIC MRI ) increased glycosaminoglycan ( GAG ) content in hyaline cartilage , which is in line with observed VAS and clinical results UNLABELLED : Osteoarthritis ( OA ) is the most widespread musculoskeletal disorder in adults . It leads to cartilage damage associated with subchondral bone changes and synovial inflammation , causing pain and disability . The present study aim ed at evaluating the safety of a dose-escalation protocol of intra-articular injected adipose-derived stromal cells ( ASCs ) in patients with knee OA , as well as clinical efficacy as secondary endpoint . A bicentric , uncontrolled , open phase I clinical trial was conducted in France and Germany with regulatory agency approval for ASC expansion procedure in both countries . From April 2012 to December 2013 , 18 consecutive patients with symptomatic and severe knee OA were treated with a single intra-articular injection of autologous ASCs . The study design consisted of three consecutive cohorts ( six patients each ) with dose escalation : low dose ( 2 × 10(6 ) cells ) , medium dose ( 10 × 10(6 ) ) , and high dose ( 50 × 10(6 ) ) . The primary outcome parameter was safety evaluated by recording adverse events throughout the trial , and secondary parameters were pain and function subscales of the Western Ontario and McMaster Universities Arthritis Index . After 6 months of follow-up , the procedure was found to be safe , and no serious adverse events were reported . Four patients experienced transient knee joint pain and swelling after local injection . Interestingly , patients treated with low-dose ASCs experienced significant improvements in pain levels and function compared with baseline . Our data suggest that the intra-articular injection of ASCs is a safe therapeutic alternative to treat severe knee OA patients . A placebo-controlled double-blind phase IIb study is being initiated to assess clinical and structural efficacy . SIGNIFICANCE Although this phase I study included a limited number of patients without a placebo arm , it showed that local injection of autologous adipose-derived stem cells was safe and well tolerated in patients with knee osteoarthritis . This study also provides encouraging preliminary evidence of efficacy . Larger and controlled long-term studies are now m and atory to confirm whether this new strategy of cell therapy can improve pain and induce structural benefit in osteoarthritis Mesenchymal stem cells ( MSCs ) are known to have a potential for articular cartilage regeneration . However , most studies focused on focal cartilage defect through surgical implantation . For the treatment of generalized cartilage loss in osteoarthritis , an alternative delivery strategy would be more appropriate . The purpose of this study was to assess the safety and efficacy of intra-articular injection of autologous adipose tissue derived MSCs ( AD-MSCs ) for knee osteoarthritis  . We enrolled 18 patients with osteoarthritis of the knee and injected AD MSCs into the knee . The phase I study consists of three dose-escalation cohorts ; the low-dose ( 1.0 × 10(7 ) cells ) , mid-dose ( 5.0 × 10(7 ) ) , and high-dose ( 1.0 × 10(8 ) ) group with three patients each . The phase II included nine patients receiving the high-dose . The primary outcomes were the safety and the Western Ontario and McMaster Universities Osteoarthritis index ( WOMAC ) at 6 months . Secondary outcomes included clinical , radiological , arthroscopic , and histological evaluations . There was no treatment-related adverse event . The WOMAC score improved at 6 months after injection in the high-dose group . The size of cartilage defect decreased while the volume of cartilage increased in the medial femoral and tibial condyles of the high-dose group . Arthroscopy showed that the size of cartilage defect decreased in the medial femoral and medial tibial condyles of the high-dose group . Histology demonstrated thick , hyaline-like cartilage regeneration . These results showed that intra-articular injection of 1.0 × 10(8 ) AD MSCs into the osteoarthritic knee improved function and pain of the knee joint without causing adverse events , and reduced cartilage defects by regeneration of hyaline-like articular cartilage BACKGROUND Microfracture is a frequently used technique for the repair of articular cartilage lesions of the knee . Despite the popularity of the technique , prospect i ve information about the clinical results after microfracture is still limited . The purpose of our study was to identify the factors that affect the clinical outcome from this cartilage repair technique . METHODS Forty-eight symptomatic patients with isolated full-thickness articular cartilage defects of the femur in a stable knee were treated with the microfracture technique . Prospect i ve evaluation of patient outcome was performed for a minimum follow-up of twenty-four months with a combination of vali date d outcome scores , subjective clinical rating , and cartilage-sensitive magnetic resonance imaging . RESULTS At the time of the latest follow-up , knee function was rated good to excellent for thirty-two patients ( 67 % ) , fair for twelve patients ( 25 % ) , and poor for four ( 8 % ) . Significant increases in the activities of daily living scores , International Knee Documentation Committee scores , and the physical component score of the Short Form-36 were demonstrated after microfracture ( p < 0.05 ) . A lower body-mass index correlated with higher scores for the activities of daily living and SF-36 physical component , with the worst results for patients with a body-mass index of > 30 kg/m(2 ) . Significant improvement in the activities of daily living score was more frequent with a preoperative duration of symptoms of less than twelve months ( p < 0.05 ) . Magnetic resonance imaging in twenty-four knees demonstrated good repair-tissue fill in the defect in thirteen patients ( 54 % ) , moderate fill in seven ( 29 % ) , and poor fill in four patients ( 17 % ) . The fill grade correlated with the knee function scores . All knees with good fill demonstrated improved knee function , whereas poor fill grade was associated with limited improvement and decreasing functional scores after twenty-four months . CONCLUSIONS Microfracture repair of articular cartilage lesions in the knee results in significant functional improvement at a minimum follow-up of two years . The best short-term results are observed with good fill grade , low body-mass index , and a short duration of preoperative symptoms . A high body-mass index adversely affects short-term outcome , and a poor fill grade is associated with limited short-term durability BACKGROUND This safety and feasibility study used autologous adipose-derived stromal vascular cells ( the stromal vascular fraction [ SVF ] of adipose tissue ) , to treat 8 osteoarthritic knees in 6 patients of grade I to III ( K-L scale ) with initial pain of 4 or greater on a 10-point Visual Analog Scale ( VAS ) . OBJECTIVES The primary objective of the study was evaluation of the safety of intra-articular injection of SVF .  The secondary objective was to assess initial feasibility for reduction of pain in osteoarthritic knees . METHODS Adipose-derived SVF cells were obtained through enzymatic disaggregation of lipoaspirate , resuspension in 3 mL of Lactated Ringer 's Solution , and injection directly into the intra-articular space of the knee , with a mean of 14.1 million viable , nucleated SVF cells per knee . Metrics included monitoring of adverse events and preoperative to postoperative changes in the Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) , the VAS pain scale , range of motion ( ROM ) , timed up- and -go ( TUG ) , and MRI . RESULTS No infections , acute pain flares , or other adverse events were reported . At 3-months postoperative , there was a statistically significant improvement in WOMAC and VAS scores ( P < .02 and P < .001 , respectively ) , which was maintained at 1 year . Physical therapy measurements for ROM and TUG both improved from preoperative to 3-months postoperative . St and ard MRI assessment from preoperative to 3-months postoperative showed no detectable structural differences . All patients attained full activity with decreased knee pain . CONCLUSIONS Autologous SVF was shown to be safe and to present a new potential therapy for reduction of pain for osteoarthritis of the knee . LEVEL OF EVIDENCE 4 : Therapeutic Cartilage defects occur in approximately 12 % of the population and can result in significant function impairment and reduction in quality of life . Evidence for the variety of surgical treatments available is inconclusive . This study aim ed to compare the clinical outcomes of patients with symptomatic cartilage defects treated with matrix-induced autologous chondrocyte implantation ( MACI ™ or microfracture ( MF ) . Included patients were ≥18 and ≤50 years of age with symptomatic , post-traumatic , single , isolated chondral defects ( 4–10 cm2 ) and were r and omised to receive MACI ™ or MF .  Patients were followed up 8–12 , 22–26 and 50–54 weeks post-operatively for efficacy and safety evaluation . Outcome measures were the Tegner , Lysholm and ICRS scores . Sixty patients were included in a r and omised study ( 40 MACI ™ , 20 MF ) . The difference between baseline and 24 months post-operatively for both treatment groups was significant for the Lysholm , Tegner , patient ICRS and surgeon ICRS scores ( all P < 0.0001 ) . However , MACI ™ was significantly more effective over time ( 24 months versus baseline ) than MF according to the Lysholm ( P = 0.005 ) , Tegner ( P = 0.04 ) , ICRS patient ( P = 0.03 ) and ICRS surgeon ( P = 0.02 ) scores . There were no safety issues related to MACI ™ or MF during the study . MACI ™ is superior to MF in the treatment of articular defects over 2 years . MACI ™ and MF are complementary procedures , depending on the size of the defect and symptom recurrence . The MACI ™ technique represents a significant advance over both first and second generation chondrocyte-based cartilage repair techniques for surgeons , patients , health care institutions and payers in terms of reproducibility , safety , intraoperative time , surgical simplicity and reduced invasiveness AIM This study aim ed to evaluate the safety and therapeutic potential of autologous human adipose-derived mesenchymal stem cells ( haMSCs ) in patients with osteoarthritis . MATERIAL S & METHODS Safety and efficacy of haMSCs were pre clinical ly assessed in vitro and in BALB/c-nu nude mice . 18 patients were enrolled and divided into three dose groups : the low-dose , mid-dose and high-dose group ( 1 × 107 , 2 × 107 and 5 × 107 cells , respectively ) , provided three injections and followed up for 96 weeks . RESULTS & CONCLUSION The pre clinical study established the safety and efficacy of  haMSCs . Intra-articular injections of haMSCs  were safe and improved pain , function and cartilage volume of the knee joint , rendering them a promising novel treatment for knee osteoarthritis . The dosage of 5 × 107 haMSCs exhibited the highest improvement ( Clinical Trials.gov Identifier : NCT01809769 )
Purpose of Review Recent studies have investigated the effect of treatments containing adipose-derived mesenchymal stem cells ( ADMSCs ) on human osteoarthritis .
These have mostly used biologic adjuvants which may influence results .
Thus , the purpose of this systematic review is to evaluate the current literature on these treatments when used in isolation .