Long term improvement of knee osteoarthritis after injection of single high/very high volume of very pure PRP: A retrospective analysis of patients optimally managed in dedicated centers.

Introduction: PRP is gaining increasing interest for pain relief and improvement of joint function in patients with knee osteoarthritis (KOA) but practices and results remain heterogeneous limiting its adoption as standard of care. Current international recommendations are to collect real-life evidence of efficacy with a systematic monitoring of PRP quality and patients' outcomes. We aimed to analyze the response of patients presenting KOA and treated with standardized PRP injection in routine care. We also investigated the potential contributing factors including patient's phenotype and PRP characteristics. Methods: Patients with symptomatic KOA and that failed first-line therapy received a single injection of a qualified PRP prepared using medical devices allowing to recover a high/very high volume of very pure PRP. Visual analogue scale (VAS) and Western Ontario and McMaster Osteoarthritis Index (WOMAC) score were recorded at baseline and during 18 months follow-up. Results: 431 patients had available follow-up data at 3 months, 291 at 6 months, 137 at 12 months and 44 at 18 months. PRP induced a significant decrease of WOMAC score at all follow up endpoints (29.2 ± 19.2 at 3 months, p < 0.001 and 25.9 ± 19.7 at 12 months, p < 0.01, compared to 39.7 ± 18.9 at baseline). Similar results were observed for pain VAS (38.9 ± 23.3 at 3 months, p < 0.001 and 35.3 ± 24.1 at 12 months, p < 0.05, compared to 56.0 ± 20.7 at baseline). Changes at 12 months were correlated to baseline scores and to the level of improvement at 3 months. The proportion of OMERACT OARSI responders reached 56.2 % for the total cohort and 60.4 % for severe patients at 6 months. Treatment failure occurred for 8.4 % of patients. Age, BMI or Kellgren-Lawrence grade did not impact on efficacy. Conclusion: This real-life study evidences the clinical benefit of a standardized high or very high-volume injection of very pure PRP in patients with KOA, including those with a severe grade. It opens perspectives in the positioning of such strategy to delay arthroplasty and provide insights on factors able to anticipate long term efficacy.

Current Fat Grafting Practices and Preferences: A Survey from Members of ISPRES.

Fat grafting has established its niche in a wide spectrum of aesthetic and reconstructive procedures. A consensus-based method of harvest, processing, enrichment, injection, and assessment is lacking, despite the rising trends in its application. We conducted a survey among plastic surgeons to evaluate and identify trends of fat grafting practices. Methods: We conducted an electronic survey with a 30-item questionnaire of 62 members of the International Society of Plastic Regenerative Surgeons. We collected demographic information, techniques, and experiences related to large volume (100-200 ml) and small-volume (<100 ml) fat grafting. Results: The majority of the respondents worked predominantly as aesthetic surgeons. The donor area selection was based on the patient's fat availability (59.7%). For fat enrichment, platelet-rich-plasma and adipose stem cells were routinely used by 12.9% and 9.7% of respondents, respectively. A 3- to 4-mm cannula with three holes was the most preferred instrument for large-volume fat harvesting (69.5%). For small-volume fat grafting, 2-mm cannulas (75.8%) with Mercedes tip (27.3%) were used most commonly. For processing, decantation of fat was performed by 56.5% of respondents (without exclusivity). For handheld injections (without exclusivity), respondents preferred a 1- to 2-mm cannula with a 1 cm3 syringe. The most popular method of outcome assessment was photographic evaluation. Conclusions: The respondents' tendencies were similar to those reported in the previous literature, with some exceptions, such as the technique for preparing fat and enrichment. A wider cross-sectional survey, involving national delegates and global representatives of plastic surgeons, is anticipated.

Adipose tissue-derived stromal vascular fraction for treating hands of patients with systemic sclerosis: a multicentre randomized trial Autologous AD-SVF versus placebo in systemic sclerosis.

OBJECTIVE: To assess the superiority of adipose tissue-derived stromal vascular fraction (AD-SVF) injection into the fingers vs placebo in reducing hand disability in systemic sclerosis (SSc) patients. METHODS: We performed a double-blind, multicentre, phase II trial from October 2015 to January 2018 in France. SSc patients with a Cochin Hand Function Scale (CHFS) ≥20/90 were randomized 1:1 to receive injection of AD-SVF or placebo. AD-SVF was obtained using the automated processing Celution 800/CRS system. The placebo was lactated Ringer's solution. The primary efficacy end point was the change of the CHFS score from baseline to 3 months. Secondary efficacy endpoints included the CHFS score at 6 months, hand function, vasculopathy, hand pain, skin fibrosis, sensitivity of the finger pulps, Scleroderma Health Assessment Questionnaire, patients and physician satisfaction, and safety. RESULTS: Forty patients were randomized. The AD-SVF and placebo groups were comparable for age, sex ratio, disease duration, skin fibrosis of the hands and main cause of hand disability. After 3 months' follow-up, hand function significantly improved in both groups with no between-group difference of CHFS (mean change of -9.2 [12.2] in the AD-SVF group vs -7.6 [13.2] in the placebo group). At 6 months, hand function improved in both groups. CONCLUSION: This study showed an improvement of hand function in both groups over time, with no superiority of the AD-SVF. Considering the limits of this trial, studies on a larger population of patients with homogeneous phenotype and hand handicap should be encouraged to accurately assess the benefit of AD-SVF therapy. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02558543. Registered on September 24, 2015.

Inter-center comparison of good manufacturing practices-compliant stromal vascular fraction and proposal for release acceptance criteria: a review of 364 productions.

BACKGROUND: Even though the manufacturing processes of the stromal vascular fraction for clinical use are performed in compliance with the good manufacturing practices applying to advanced therapy medicinal products, specifications related to stromal vascular fraction quality remain poorly defined. We analyzed stromal vascular fraction clinical batches from two independent good manufacturing practices-compliant manufacturing facilities, the Swiss Stem Cell Foundation (SSCF) and Marseille University Hospitals (AP-HM), with the goal of defining appropriate and harmonized release acceptance criteria. METHODS: This retrospective analysis reviewed the biological characteristics of 364 batches of clinical-grade stromal vascular fraction. Collected data included cell viability, recovery yield, cell subset distribution of stromal vascular fraction, and microbiological quality. RESULTS: Stromal vascular fraction from SSCF cohort demonstrated a higher viability (89.33% ± 4.30%) and recovery yield (2.54 × 105 ± 1.22 × 105 viable nucleated cells (VNCs) per mL of adipose tissue) than stromal vascular fraction from AP-HM (84.20% ± 5.96% and 2.25 × 105 ± 1.11 × 105 VNCs per mL). AP-HM batches were significantly less contaminated (95.71% of sterile batches versus 74.15% for SSCF batches). The cell subset distribution was significantly different (higher proportion of endothelial cells and lower proportion of leukocytes and pericytes in SSCF cohort). CONCLUSIONS: Both centers agreed that a good manufacturing practices-compliant stromal vascular fraction batch should exert a viability equal or superior to 80%, a minimum recovery yield of 1.50 × 105 VNCs per mL of adipose tissue, a proportion of adipose-derived stromal cells at least equal to 20%, and a proportion of leukocytes under 50%. In addition, a multiparameter gating strategy for stromal vascular fraction analysis is proposed.

A Retrospective Analysis of Characteristic Features of Responders and Impaired Patients to a Single Injection of Pure Platelet-Rich Plasma in Knee Osteoarthritis.

(1) Background: The emergence of injectable "biologic" medication creates a new approach to treat osteoarthritis (OA). Among them, the use of intra-articular injection of PRP became widespread despite the absence of consensus regarding its optimal composition. The aim of this study was to retrospectively correlate an extensive biological characterization of injected PRP to the clinical responses of patients presenting knee OA. (2) Methods: This retrospective study included 75 patients with knee OA. Cartilage lesions were assessed using magnetic resonance imaging and the International Cartilage Regeneration Society (ICRS) classification. PRP extensive biological characterization was performed and patients' subjective symptoms were recorded before injection and 3 and 6 months after injection using the Knee injury and Osteoarthritis Outcome Score (KOOS). Responders were defined by an improvement of 10 points on KOOS. (3) Results: At 6 months, 63.0% of the patients were responders. Impairment was characterized by a significantly higher proportion of patients with three compartments altered at baseline MRI and receiving a significantly higher dose of platelets compared to responders. (4) Conclusions: Single injection of pure PRP resulted in significant clinical improvement in the management of knee OA. Both baseline MRI and PRP biological features may be predictive factors of the clinical response, highlighting that a better understanding of action mechanism of PRP is still required.

AIRMESS - Academy of International Regenerative Medicine & Surgery Societies: recommendations in the use of platelet-rich plasma (PRP), autologous stem cell-based therapy (ASC-BT) in androgenetic alopecia and wound healing.

INTRODUCTION: Many investigations showed that platelet-rich plasma (PRP), human follicles stem cells (HFSCs), and adipose-derived stem cells (ASCs), considered autologous stem cell-based therapy (ASC-BT), are effective for hair regrowth (HR) in patients affected by androgenetic alopecia and for wound healing (WH). The aim of this article is to analyze the in vitro and in vivo impact of different PRP, HFSCs, and ASCs preparation methods on HR and in WH. AREAS COVERED: The analyzed data intended to clarify the molecular mechanism in which PRP, HFSCs, and ASCs are involved, the clinical use and related indications, fully respecting the European rules. Comparative studies between different systems of PRP, HFSCs, and ASCs preparation revealed differences in terms of HR and WH. EXPERT OPINION: Despite a lack of standardized protocols, there is convincing evidence with objective measurement modalities that display positive outcomes of ASC-BT in HR and WH.

Microfat and Nanofat Grafting in Genital Rejuvenation.

BACKGROUND: Genitourinary syndrome of menopause (GSM) is a major problem in many post- or perimenopausal women. Lipofilling has long been considered to be an effective technique for restoring volume, but the discovery of its trophic proprieties has made it the most widely utilized method in regenerative medicine. OBJECTIVES: The authors aimed to assess the safety and efficacy of microfat and nanofat grafting for vulvovaginal rejuvenation. METHODS: Women with GSM who met the inclusion criteria were enrolled. Women received microfat in the labia majora and nanofat in the vagina; follow-up was conducted 1, 3, 6, 12, and 18 months. The vaginal health index (VHI) and Female Sexual Distress (FSD) were utilized to assess improvement in vulvovaginal atrophy, orgasm, and sexual desire posttreatment. RESULTS: Fifty women were included; their average age was 53 years (range, 45-63 years). The VHI score significantly increased at 1 and 3 months after treatment (P < 0.0001). Moreover, the average FSD score showed a significant improvement at 1 and 3 months posttreatment. This score stabilized from 6 to 12 months but showed further improvement at 18 months. At 6 months posttreatment, for both scales, data pertaining to 80% of patients appeared normalized. There was a particular benefit noted for dryness and dyspareunia. At 18 months, the results remained stable for all of patients. No major side effects were observed. CONCLUSIONS: There are now many ways to rejuvenate the intimate sphere, but microfat and nanofat grafting seem to offer good results with an autologous procedure. Their utilization appears promising for genital rejuvenation.

Fat Grafting for Treatment of Facial Scleroderma.

Reparative, angiogenic, and immunomodulatory properties have been attributed to the cells in the adipose tissue-derived stromal vascular fraction. Because of these characteristics, in the last decade, fat grafting for treatment of autoimmune diseases has grown. This article focuses on systemic sclerosis, a rare autoimmune disease characterized by skin fibrosis and microvascular damage. Lesions of the face are almost always present; however, current therapy is insufficient and patients have considerable disability and social discomfort. This article presents our approach to using fat grafting in the face as an innovative and promising therapy for patients with systemic sclerosis.

Intraoperative Strategies for Minimal Manipulation of Autologous Adipose Tissue for Cell- and Tissue-Based Therapies: Concise Review.

The stromal vascular fraction (SVF) is a heterogeneous population of stem/stromal cells isolated from perivascular and extracellular matrix (ECM) of adipose tissue complex (ATC). Administration of SVF holds a strong therapeutic potential for regenerative and wound healing medicine applications aimed at functional restoration of tissues damaged by injuries or chronic diseases. SVF is commonly divided into cellular stromal vascular fraction (cSVF) and tissue stromal vascular fraction (tSVF). Cellular SVF is obtained from ATC by collagenase digestion, incubation/isolation, and pelletized by centrifugation. Enzymatic disaggregation may alter the relevant biological characteristics of adipose tissue, while providing release of complex, multiattachment of cell-to-cell and cell-to-matrix, effectively eliminating the bioactive ECM and periadventitial attachments. In many countries, the isolation of cellular elements is considered as a "more than minimal" manipulation, and is most often limited to controlled clinical trials and subject to regulatory review. Several alternative, nonenzymatic methods of adipose tissue processing have been developed to obtain via minimal mechanical manipulation an autologous tSVF product intended for delivery, reducing the procedure duration, lowering production costs, decreasing regulatory burden, and shortening the translation into the clinical setting. Ideally, these procedures might allow for the integration of harvesting and processing of adipose tissue for ease of injection, in a single procedure utilizing a nonexpanded cellular product at the point of care, while permitting intraoperative autologous cellular and tissue-based therapies. Here, we review and discuss the options, advantages, and limitations of the major strategies alternative to enzymatic processing currently developed for minimal manipulation of adipose tissue. Stem Cells Translational Medicine 2019;8:1265&1271.

Fluid Cartilage as New Autologous Biomaterial in the Treatment of Minor Nose Defects: Clinical and Microscopic Difference Amongst Diced, Crushed, and Fluid Cartilage.

Developing cartilage constructs with injectability, appropriate matrix composition, and persistent cartilaginous phenotype remains an enduring challenge in cartilage repair. Fourteen patients with minor contour deformity were treated with fluid cartilage filler gently injected as autologous fluid graft in deep planes of defect of the nose that were close to the bone or the cartilage. A computerized tomographic scan control was performed after 12 months. Pearson's Chi-square test was used to investigate differences in cartilage density between native and newly formed cartilages. The endpoints were the possibility of using fluid cartilage as filler with aesthetic and functional improvement and versatility. Patients were followed up for two years. The constructs of fluid cartilage graft that were injected in the deep plane resulted in a persistent cartilage tissue with appropriate morphology, adequate central nutritional perfusion without central necrosis or ossification, and further augmented nasal dorsum without obvious contraction and deformation. This report demonstrated that fluid cartilage grafts are useful for cartilage regeneration in patients with outcomes of rhinoplasty, internal nasal valve collapse, and minor congenital nose aesthetics deformity.

First clinical case report of local microinjection of autologous fat and adipose-derived stromal vascular fraction for perianal fistula in Crohn's disease.

Mesenchymal stem cell therapy is a promising treatment for perianal Crohn's fistulas refractory to conventional therapy, which are an extremely morbid complication and a true therapeutic challenge. Autologous adipose-derived stromal vascular fraction (ADSVF) is an easily accessible source of cells with angiogenic, anti-inflammatory, immunomodulatory, and regenerative properties. Here, we describe a case involving a patient with severe perianal Crohn's fistulas refractory to the best medical and surgical practices who received local treatment with ADSVF and microfat. This patient was first examined under anesthesia with drainage via seton placement; 1 week later, on a single day, he underwent adipose tissue extraction, ADSVF and microfat preparation, and the local injection of 14 ml of microfat and approximately 20 million viable ADSVF cells into the soft tissue around the fistulas. No serious adverse events were observed. At the first endpoint at 12 weeks, the fistula had clinically healed with complete re-epithelialization of all external openings; no fistula tract was detected on magnetic resonance imaging, confirming this finding. This good clinical outcome was sustained at 48 weeks and was associated with a reduction in the severity of perianal disease and an improvement in quality of life. The current case highlights the therapeutic potential of a new cellular treatment for Crohn's patients with refractory perianal fistulas based on the innovative hypothesis that the combined action of ADSVF in association with the trophic characteristics of a microfat graft could be beneficial for this condition. TRIAL REGISTRATION: EudraCT number 201325, NCT02520843 . Registered on 5 August 2015.

Intra-articular Injection of Mesenchymal Stem Cells and Platelet-Rich Plasma to Treat Patellofemoral Osteoarthritis: Preliminary Results of a Long-Term Pilot Study.

PURPOSE: To assess the feasibility and safety of concomitant intra-articular (IA) knee injection of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) under fluoroscopic guidance to treat patellofemoral osteoarthritis (OA). MATERIALS AND METHODS: This prospective study included 19 consecutive patients referred for fluoroscopically guided IA MSC and PRP injection for symptomatic patellofemoral chondropathy in which conservative treatment had failed. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and magnetic resonance (MR) data, including T2 mapping sequence, were prospectively collected before and 6 months after treatment. Clinical data without MR imaging were collected until 12 months after the procedure. RESULTS: WOMAC scores were significantly lower after IA injection of MSCs and PRP at 6 months and during 12-months follow-up compared with baseline (mean score decreased from 34.3 to 14.2; P < .0018). Patients reported no complications. Concerning MR imaging follow-up, there were no significant differences in grade, surface, or T2 value of the chondral lesions (P > .375). CONCLUSIONS: IA injection of MSCs and PRP in early patellofemoral OA appears to allow functional improvement.

Combined use of platelet rich plasma & micro-fat in sport and race horses with degenerative joint disease: preliminary clinical study in eight horses.

BACKGROUND: To assess the safety and potential efficacy of a standardized technique consisting of intra-articular injection of 10 cc of a homogeneous mixed product using autologous micro-fat and platelet rich plasma (PRP) (ratio 1:1) in the carpus or the fetlock joint of sport horses presenting degenerative joint disease (DJD). METHODS: Eight sport horses with DJD confirmed by radiography and ultrasonography and causing lameness and the impossibility to compete were treated. PRP was prepared after a double centrifugation whereas micro-fat was harvested and purified using a closed system. The two products were connected and mixed by gentle back and forth shaking of the syringes to finally obtain 10 ml of an homogeneous mixed product. Follow up was performed from 5 to 10 months with assessment of AAEP lameness score and return to training and competition. RESULTS: Nine joints were treated with significant improvement of the AAEP lameness score three months after the procedure (p = 0.021). Four horses returned to official competition between 5 to 10 months after the procedure (7.0±2.5) and three of them resumed intensive training between 5 to 9 months (6.3±2.3). No adverse event occurred. CONCLUSION: This study is a first step in the development of innovative therapy for DJD which combines the potential chondrogenic differentiation of MSCs inside equine adipose tissue with the proliferative effect of growth factors present in PRP.

Efficacy of Autologous Microfat Graft on Facial Handicap in Systemic Sclerosis Patients.

BACKGROUND: Autologous adipose tissue injection is used in plastic surgery for correction of localized tissue atrophy and has also been successfully offered for treatment of localized scleroderma. We aimed to evaluate whether patients with systemic sclerosis (SSc) and facial handicap could also benefit from this therapy. METHODS: We included 14 patients (mean age of 53.8 ± 9.6 years) suffering from SSc with facial handicap defined by Mouth Handicap in Systemic Sclerosis Scale (MHISS) score more than or equal to 20, a Rodnan skin score on the face more than or equal to 1, and maximal mouth opening of less than 55 mm. Autologous adipose tissue injection was performed under local anesthesia using the technique of subcutaneous microinjection. The main objective of this study was an improvement of the MHISS score 6 months after the surgical treatment. RESULTS: The procedure was well tolerated. We observed a mean decrease in the MHISS score of 10.7 points (±5.1; P < 0.0001) at 6 months (35% improvement). Secondary efficacy parameters assessing perioral skin sclerosis, maximum mouth opening, sicca syndrome, and facial pain significantly improved at 3 and 6 months postsurgery. At a 6-month follow-up, 75% of patients were satisfied or very satisfied of the adipose tissue microinjection therapy. CONCLUSIONS: Our study suggests that subcutaneous perioral microfat injection in patients with SSc is beneficial in the treatment of facial handicap, skin sclerosis, mouth opening limitation, sicca syndrome, and facial pain. Thus, this minimally invasive approach offers a new hope for face therapy for patients with SSc.

Histological and Urodynamic Effects of Autologous Stromal Vascular Fraction Extracted from Fat Tissue with Minimal Ex Vivo Manipulation in a Porcine Model of Intrinsic Sphincter Deficiency.

PURPOSE: To evaluate the healing abilities of autologous stem cell therapy (stromal vascular fraction) prepared from adipose tissue we used an automated system without an ex vivo culture phase in a pig model of intrinsic sphincteric deficiency. MATERIALS AND METHODS: A total of 15 pigs underwent endoscopic section of the urethral sphincter. Animals were then randomly assigned to 3 groups, including 1) controls without stromal vascular fraction injection, 2) early injection with stromal vascular fraction 2 to 3 days after section and 3) late stromal vascular fraction injection delivery 30 days after injury. Extraction and stromal vascular fraction injection were performed as a single procedure. The stromal vascular fraction was characterized by flow cytometry. Mesenchymal stem cell-like cells were enumerated by clonogenicity (cfu fibroblast) assay. Study end points included histological assessment of the urethral injury surface and urodynamics to determine maximum urethral pressure. RESULTS: Flow cytometry analysis revealed a mesenchymal stem cell-like phenotype in a mean ± SD of 47.3% ± 11.8% of stromal vascular fraction cells. The cfu fibroblast frequency was 1.3 to 6.6/100 stromal vascular fraction cells (1.3% to 6.6%). Stromal vascular fraction injection was associated with a reduction of the urethral injury surface in the early and late injection groups compared with the respective controls (7% vs 17% and 1% vs 13%, p = 0.050 and 0.029, respectively). On day 30 after injection maximum urethral pressure was significantly higher in the injected groups than in the control group, that is 64% vs 50% of maximum urethral pressure on day 0 (p = 0.04). CONCLUSIONS: These data demonstrate the ability of an autologous stromal vascular fraction to improve the urethral healing process in a large animal model of intrinsic sphincteric deficiency.

Comparison between Stromal Vascular Fraction and Adipose Mesenchymal Stem Cells in Remodeling Hypertrophic Scars.

Hypertrophic scars (HTS) are characterized by excessive amount of collagen deposition and principally occur following burn injuries or surgeries. In absence of effective treatments, the use of mesenchymal stem/stromal cells, which have been shown to attenuate fibrosis in various applications, seems of interest. The objectives of the present study were therefore to evaluate the effect of human adipose tissue-derived mesenchymal stem cells (hASC) on a pre-existing HTS in a humanized skin graft model in Nude mice and to compare the efficacy of hASCs versus stromal vascular fraction (SVF). We found that injection of SVF or hASCs resulted in an attenuation of HTS as noticed after clinical evaluation of skin thickness, which was associated with lower total collagen contents in the skins of treated mice and a reduced dermis thickness after histological analysis. Although both SVF and hASCs were able to significantly reduce the clinical and histological parameters of HTS, hASCs appeared to be more efficient than SVF. The therapeutic effect of hASCs was attributed to higher expression of TGFß3 and HGF, which are important anti-fibrotic mediators, and to higher levels of MMP-2 and MMP-2/TIMP-2 ratio, which reflect the remodelling activity responsible for fibrosis resorption. These results demonstrated the therapeutic potential of hASCs for clinical applications of hypertrophic scarring.

Effectiveness of pure argon for renal transplant preservation in a preclinical pig model of heterotopic autotransplantation.

BACKGROUND: In kidney transplantation, the conditions of organ preservation following removal influence function recovery. Current static preservation procedures are generally based on immersion in a cold-storage solution used under atmospheric air (approximately 78 kPa N2, 21 kPa O2, 1 kPa Ar). Research on static cold-preservation solutions has stalled, and modifying the gas composition of the storage medium for improving preservation was considered. Organoprotective strategies successfully used noble gases and we addressed here the effects of argon and xenon on graft preservation in an established preclinical pig model of autotransplantation. METHODS: The preservation solution Celsior saturated with pure argon (Argon-Celsior) or xenon (Xenon-Celsior) at atmospheric pressure was tested versus Celsior saturated with atmospheric air (Air-Celsior). The left kidney was removed, and Air-Celsior (n = 8 pigs), Argon-Celsior (n = 8) or Xenon-Celsior (n = 6) was used at 4 °C to flush and store the transplant for 30 h, a duration that induced ischemic injury in our model when Air-Celsior was used. Heterotopic autotransplantation and contralateral nephrectomy were performed. Animals were followed for 21 days. RESULTS: The use of Argon-Celsior vs. Air-Celsior: (1) improved function recovery as monitored via creatinine clearance, the fraction of excreted sodium and tubulopathy duration; (2) enabled diuresis recovery 2-3 days earlier; (3) improved survival (7/8 vs. 3/8 pigs survived at postoperative day-21); (4) decreased tubular necrosis, interstitial fibrosis, apoptosis and inflammation, and preserved tissue structures as observed after the natural death/euthanasia; (5) stimulated plasma antioxidant defences during the days following transplantation as shown by monitoring the "reduced ascorbic acid/thiobarbituric acid reactive substances" ratio and Hsp27 expression; (6) limited the inflammatory response as shown by expression of TNF-alpha, IL1-beta and IL6 as observed after the natural death/euthanasia. Conversely, Xenon-Celsior was detrimental, no animal surviving by day-8 in a context where functional recovery, renal tissue properties and the antioxidant and inflammation responses were significantly altered. Thus, the positive effects of argon were not attributable to the noble gases as a group. CONCLUSIONS: The saturation of Celsior with argon improved early functional recovery, graft quality and survival. Manipulating the gas composition of a preservation medium constitutes therefore a promising approach to improve preservation.

Autologous adipose-derived stromal vascular fraction in patients with systemic sclerosis: 12-month follow-up.

OBJECTIVE: Impaired hand function greatly contributes to disability and reduced quality of life in SSc patients. Autologous adipose-derived stromal vascular fraction (ADSVF) is recognized as an easily accessible source of regenerative cells. We reported positive 6-month safety and efficacy results from an open-label clinical trial assessing s.c. injection of autologous ADSVF into the fingers in SSc patients. The objective of this report is to describe the effects at 12 months. METHODS: Twelve females, mean age 54.5 years (s.d. 10.3), were assessed 1 year after ADSVF injection. Patients were eligible if they had a Cochin Hand Function Scale score >20/90. ADSVF was obtained from lipoaspirate using an automated processing system and subsequently injected into the s.c. tissue of each finger in contact with neurovascular pedicles in a one-time procedure. Endpoints were changes in hand disability and skin fibrosis, vascular manifestations, pain and quality of life at the 12 month follow-up. During the visit, patients estimated the benefit of the procedure with a specific self-completed questionnaire. RESULTS: A significant decrease from baseline of 51.3% (P < 0.001) for Cochin Hand Function Scale score, 63.2% (P < 0.001) for RP severity and 46.8% (P = 0.001) for quality of life (Scleroderma Health Assessment Questionnaire) was observed. A significant improvement of finger oedema, skin sclerosis, motion and strength of the hands and of the vascular suppression score was also noted. The reduction in hand pain approached statistical significance (P = 0.052). The questionnaire revealed a benefit in daily activities, housework and social activities. CONCLUSION: ADSVF injection is a promising therapy and appears to have benefits that extend for at least 1 year.