Publications by authors named "Fanny Grimaud"

17 Publications

  • Page 1 of 1

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

J Clin Med 2021 Apr 17;10(8). Epub 2021 Apr 17.

Cell Therapy Laboratory, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, 13005 Marseille, France.

(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.
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http://dx.doi.org/10.3390/jcm10081748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073986PMC
April 2021

Intra Articular Injection Of Autologous Microfat And Platelet-Rich Plasma In The Treatment Of Knee Osteoarthritis: A Double Blind Randomized Comparative Study.

Arthroscopy 2021 Apr 19. Epub 2021 Apr 19.

Cell Therapy Laboratory, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, Marseille, France; Aix Marseille Univ, INSERM, INRA, C2VN, Marseille, France. Electronic address:

Purpose: Compare a single abdominal microfat (MF) injection mixed or not with PRP Low Dose (LD) or High Dose (HD) in order to improve MRI parameters and alleviate pain and enhance functional capacity in knee osteoarthritis (OA).

Methods: Patients with symptomatic grade 2 to 4 knee OA according to the International Cartilage Repair Society MRI classification were selected. They were prospectively assessed at baseline, at 3 and 6 months of follow-up. The primary endpoint was the change in maximum of value of cartilage relaxation time in T2 mapping sequences (T2max) at 3 months. Secondary endpoints were MRI grade severity and joint space assessment, WOMAC score, pain evaluation, knee range of motion and patient's satisfaction. Adverse events were also collected. The complete cell counts and growth factors content of injected products were assessed to analyze their potential relationship with MRI/clinical outcomes.

Results: Three groups of 10 patients received a single injection of 10 cc of a mix (1:1) containing either MF-Saline, MF-PRP LD or MF-PRP HD. T2max did not change significantly over the time for any of the groups. All treatments significantly improved knee functional status and symptoms relief at 3 and 6 months. All patients were responders in the MF/PRP HD at 3 months and significantly higher compared to MF/PRP LD. Half of the injected PRP in the MF/PRP LD group displayed RBCs contamination over 8% which was correlated with an impairment of T2max.

Conclusion: A single intra articular injection of MF with or without PRP is safe and may offer a significant clinical improvement in patients with OA.
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http://dx.doi.org/10.1016/j.arthro.2021.03.074DOI Listing
April 2021

Technical and biological review of authorized medical devices for platelets-rich plasma preparation in the field of regenerative medicine.

Platelets 2021 Feb 6;32(2):200-208. Epub 2020 Nov 6.

Cell Therapy Laboratory, Hôpital De La Conception, AP-HM, Marseille, France.

Platelet-rich plasma (PRP) has seen increased interest and utilization over the past decade, particularly in the field of musculoskeletal disease. This growth has been accompanied by the development of medical devices to realize PRP preparation which includes blood collection, centrifugation, and PRP isolation. The final PRP composition is directly influenced by this preparation step and absence of biological quality control led to a lack of comparability between PRP products that could explain the large variability in the clinical benefit of PRP reported in literature. To circumvent this issue, the scientific community developed different PRP classifications but none of them have been adopted. The goal of this review is to furnish both technical and biological characteristics from PRP commercial systems. On review of 1379 studies, 105 studies were selected according to inclusion criteria for technical analysis and led to the identification of 50 commercial systems that have been classified in three technical categories based on the blood harvesting technique (tubes, syringes or bags). Twelve studies were selected and sufficiently describe biological characteristics from only 14 commercial systems from the 50 identified in the technical analysis. Inclusion of duplicates characterization from a same PRP system lead to the final analysis of 36 PRP preparations that met the inclusion criteria of the biological analysis. All these PRP preparations have been classified among the seven existing classifications. Comparison from all biological parameters and classifications revealed a large heterogeneity among the available current PRP commercial systems. Index of biological sensitivity of classifications to distinguish PRP preparations were also variable. Although these findings should help clinicians in selecting a system that meets their specific needs, this also raises the question to standardize the parameters to biologically define PRP preparation among users and to systematically performed PRP qualification when used.
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http://dx.doi.org/10.1080/09537104.2020.1832653DOI Listing
February 2021

Development and Validation of a Fully GMP-Compliant Process for Manufacturing Stromal Vascular Fraction: A Cost-Effective Alternative to Automated Methods.

Cells 2020 09 24;9(10). Epub 2020 Sep 24.

Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, 13005 Marseille, France.

The therapeutic use of adipose-derived stromal vascular fraction (SVF) is expanding in multiple pathologies. Various processes have been proposed for manufacturing SVF but they must be revisited based on advanced therapy medicinal product (ATMP) regulations. We report here the development and validation of a fully good manufacturing practices (GMP)-compliant protocol for the isolation of SVF. Adipose tissue was collected from healthy volunteers undergoing lipoaspiration. The optimal conditions of collagenase digestion and washing were determined based on measurements of SVF cell viability, yield recovery, and cell subset distribution. Comparability of the SVF obtained using the newly developed manufacturing process (n = 6) and the Celution-based automated method (n = 33), used as a reference, was established using inter-donor analyses. Characteristics of SVF (n = 5) generated using both manufacturing protocols were analyzed for an intra-donor comparison. In addition, these comparisons also included the determination of colony-forming unit fibroblast frequency, in vitro angiogenic activity, and in vivo regenerative effects in a mouse ischemic cutaneous wound model. We successfully developed a process for the generation of SVF presenting higher cell viability and yield recovery compared to the Celution device-based protocol. Characteristics of the SVF including phenotype, capacity for angiogenesis, and wound-healing promotion attested to the comparability of the two manufacturing processes. We validated an optimized non-automated process that should allow for a GMP-compliant, more affordable, and reduced-cost strategy to exploit the potential of SVF-based regenerative therapies.
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http://dx.doi.org/10.3390/cells9102158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598595PMC
September 2020

Platelet-rich plasma preparations in sports rehabilitation: Where we started and where we should go.

Ann Phys Rehabil Med 2020 Oct 18:101414. Epub 2020 Oct 18.

Cell therapy laboratory, Inserm CIC BT 1409, hôpital de la Conception, AP-HM, Marseille, France; Inserm, Inra, C2VN, Aix Marseille université, Marseille, France.

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http://dx.doi.org/10.1016/j.rehab.2020.06.003DOI Listing
October 2020

Feasibility of First Injection of Autologous Adipose Tissue-Derived Stromal Vascular Fraction in Human Scarred Vocal Folds: A Nonrandomized Controlled Trial.

JAMA Otolaryngol Head Neck Surg 2020 04;146(4):355-363

Department of Oto-Rhino-Laryngology and Head and Neck Surgery, Assistance Publique-Hôpitaux de Marseille, La Conception University Hospital, Marseille, France.

Importance: Patients with scarred vocal folds, whether congenitally or after phonosurgery, often exhibit dysphonia that negatively affects daily life and is difficult to treat. The autologous adipose tissue-derived stromal vascular fraction (ADSVF) is a readily accessible source of cells with angiogenic, anti-inflammatory, immunomodulatory, and regenerative properties.

Objective: To evaluate the feasibility and tolerability of local injections of autologous ADSVF in patients with scarred vocal folds.

Design, Setting, And Participants: CELLCORDES (Innovative Treatment for Scarred Vocal Cords by Local Injection of Autologous Stromal Vascular Fraction) is a prospective, open-label, single-arm, single-center, nonrandomized controlled trial with a 12-month follow-up and patient enrollment from April 1, 2016, to June 30, 2017. Eight patients with severe dysphonia attributable to vocal fold scarring associated with a congenital malformation or resulting from microsurgical sequelae (voice handicap index score >60 of 120) completed the study. Data analysis was performed from September 1, 2018, to January 1, 2019.

Interventions: Injection of ADSVF into 1 or 2 vocal folds.

Main Outcomes And Measures: The primary outcomes were feasibility and the number and severity of adverse events associated with ADSVF-based therapy. The secondary outcomes were changes in vocal assessment, videolaryngostroboscopy, self-evaluation of dysphonia, and quality of life at 1, 6, and 12 months after cell therapy.

Results: Seven women and 1 man (mean [SD] age, 44.6 [10.4] years) were enrolled in this study. Adverse events associated with liposuction and ADSVF injection occurred; most of them resolved spontaneously. One patient received minor treatment to drain local bruising, and another experienced a minor contour defect at the liposuction site. At 12 months, the voice handicap index score was improved in all patients, with a mean (SD) improvement from baseline of 40.1 (21.5) points. Seven patients (88%) were considered to be responders, defined as improvement by 18 points or more in the voice handicap index score (the minimum clinically important difference).

Conclusions And Relevance: The findings suggest that autologous ADSVF injection in scarred vocal folds is feasible and tolerable. The findings require confirmation in a randomized clinical trial with a larger population.

Trial Registration: ClinicalTrials.gov Identifier: NCT02622464.
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http://dx.doi.org/10.1001/jamaoto.2019.4328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163407PMC
April 2020

Adipose-Derived Therapeutic Products for the Management of Refractory Crohn's Fistula.

Gastroenterology 2019 12 19;157(6):1690-1691. Epub 2019 Sep 19.

Cell Therapy Department, INSERM CBT 1409, Assistance Publique Hôpitaux de Marseille, Aix Marseille University, Marseille, France; Faculté de Pharmacie de Marseille, INSERM, INRA, C2VN, Faculté de Pharmacie de Marseille, Aix Marseille University, Marseille, France.

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http://dx.doi.org/10.1053/j.gastro.2019.05.078DOI Listing
December 2019

A retrospective analysis of characteristic features of responder patients to autologous serum eye drops in routine care.

Ocul Surf 2019 10 16;17(4):787-792. Epub 2019 May 16.

Cell Therapy Laboratory, CBT-1409, INSERM, Assistance Publique Hôpitaux de Marseille, Marseille, France; Aix Marseille Univ, INSERM, INRA, C2VN, Marseille, France. Electronic address:

Purpose: Autologous serum eye drops (ASEDs) are used worldwide to treat dry eye disease (DED). However, the biological composition of ASEDs has not been well investigated, and effectiveness predictive factors remain to be identified. The main objective of this study was to compare the response of patients treated with ASEDs biologically characterized and used for DED routine care.

Methods: This retrospective observational study was conducted in a single university hospital, and included 50 patients (87 eyes) with DED refractory to conventional treatment and resulting from various etiologies with Ocular Surface Disease Index (OSDI) ≥ 20. Each patient used eight drops a day per treated eye with 20% diluted ASEDs. Undiluted serum extensive biological characterizations were performed, and symptoms were recorded before the initiation of ASEDs and closer to the sixth month of treatment. Responders were defined as presenting an improvement from baseline ≥14 points in OSDI and/or ≥1 grade in corneal fluorescence staining for all eyes treated.

Results: The OSDI and the Oxford scale were significantly reduced from 68.7 ± 23.2 to 54.8 ± 25.7 and 3.2 ± 1.5 to 2.1 ± 1.3 (p ≤ 0.0001), respectively. A total of 68% of the patients were responders. Nonresponding patients had significantly higher epidermal growth factor concentrations in the serum compared to responders (p = 0.017).

Conclusions: ASED administration resulted in significant clinical improvement in the management of DED. Biological differences observed between responders and nonresponders suggested that a better understanding of the biological activity of ASEDs is still required.
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http://dx.doi.org/10.1016/j.jtos.2019.05.003DOI Listing
October 2019

Development of Autologous Platelet-Rich Plasma Mixed-Microfat as an Advanced Therapy Medicinal Product for Intra-Articular Injection of Radio-Carpal Osteoarthritis: From Validation Data to Preliminary Clinical Results.

Int J Mol Sci 2019 Mar 5;20(5). Epub 2019 Mar 5.

Cell therapy department, Assistance Publique⁻Hôpitaux de Marseille, INSERM, CBT-1409, La Conception University Hospital, Marseille 13005, France.

Wrist osteoarthritis (OA) is one of the most common conditions encountered by hand surgeons with limited efficacy of non-surgical treatments. The purpose of this study is to describe the Platelet-Rich Plasma (PRP) mixed-microfat biological characteristics of an experimental Advanced Therapy Medicinal Product (ATMP) needed for clinical trial authorization and describe the clinical results obtained from our first three patients 12 months after treatment (NCT03164122). Biological characterization of microfat, PRP and mixture were analysed in vitro according to validated methods. Patients with stage four OA according to the Kellgren Lawrence classification, with failure to conservative treatment and a persistent daily painful condition >40 mm according to the visual analog scale (VAS) were treated. Microfat-PRP ATMP is a product with high platelet purity, conserved viability of stromal vascular fraction cells, chondrogenic differentiation capacity in vitro and high secretion of IL-1Ra anti-inflammatory cytokine. For patients, the only side effect was pain at the adipose tissue harvesting sites. Potential efficacy was observed with a pain decrease of over 50% (per VAS score) and the achievement of minimal clinically important differences for DASH and PRWE functional scores at one year in all three patients. Microfat-PRP ATMP presented a good safety profile after an injection in wrist OA. Efficacy trials are necessary to assess whether this innovative strategy could delay the necessity to perform non-conservative surgery.
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http://dx.doi.org/10.3390/ijms20051111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429478PMC
March 2019

Long-term Safety and Efficacy of Local Microinjection Combining Autologous Microfat and Adipose-Derived Stromal Vascular Fraction for the Treatment of Refractory Perianal Fistula in Crohn's Disease.

Gastroenterology 2019 06 18;156(8):2335-2337.e2. Epub 2019 Jan 18.

Gastroenterology Department, Assistance Publique Hôpitaux de Marseille, Centre Hospitalier Universitaire of Marseille, Marseille, France; Centre d'Investigation Clinique 1409, Assistance Publique Hôpitaux de Marseille, Aix Marseille University, France.

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http://dx.doi.org/10.1053/j.gastro.2019.01.032DOI Listing
June 2019

Use of platelet-rich plasma in regenerative medicine: technical tools for correct quality control.

BMJ Open Sport Exerc Med 2018 13;4(1):e000442. Epub 2018 Nov 13.

Cell Therapy Laboratory, CBT-1409, INSERM, Assistance Publique Hôpitaux de Marseille, Marseille, France.

Background/aims: Platelet-rich plasma (PRP) injections are used in sports medicine and have been the subject of increased clinical interest. However, there have been very few reports of the composition of initial whole blood and the final PRP product. The objective of this study was to provide technical tools to perform a correct characterisation of platelets, leucocytes and red blood cells (RBCs) from whole blood and PRP.

Methods: Blood and PRP were obtained from 26 healthy volunteers and prepared according to the varying parameters encountered within PRP process preparation and quantification (harvesting method, anticoagulant used, sampling method, counting method). Concentrations were measured at t=0, t=1, t=6  and t=24  hours.

Results: Sampling of blood in Eppendorf tubes significantly decreased platelet concentration over time, whereas sampling in Microvette EDTA-coated tube kept platelet concentration stable until 24  hours. A non-significant difference was observed in platelet counts in PRP with impedance (median (IQR): 521.8  G/L (505.3-524.7)) and fluorescence (591.5  G/L (581.5-595.8)) methods. Other studied parameters did not influence platelet concentrations in blood or PRP samples. Leucocytes and RBC counts were similar whatever the anticoagulant, sampling, harvesting and counting methods used for both blood and PRP samples.

Conclusions: Systematic sampling of blood and PRP in EDTA-coated tubes for quality control is recommended. The use of a validated counter for PRP sample should also be taken into account.
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http://dx.doi.org/10.1136/bmjsem-2018-000442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6241975PMC
November 2018

Autologous adipose-derived stromal vascular fraction and scarred vocal folds: first clinical case report.

Stem Cell Res Ther 2018 07 27;9(1):202. Epub 2018 Jul 27.

Department of Oto-Rhino-Laryngology and Head and Neck Surgery, Assistance Publique-Hôpitaux de Marseille, La Conception University Hospital, 13385 Cedex, Marseille, France.

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http://dx.doi.org/10.1186/s13287-018-0842-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062967PMC
July 2018

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

Stem Cell Res Ther 2018 01 10;9(1). Epub 2018 Jan 10.

Culture and Cell Therapy Laboratory, INSERM CBT-1409, APHM, Aix Marseille University, Marseille, France.

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.
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http://dx.doi.org/10.1186/s13287-017-0736-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764003PMC
January 2018

European Maxillofacial Trauma (EURMAT) in children: a multicenter and prospective study.

Oral Surg Oral Med Oral Pathol Oral Radiol 2015 May 24;119(5):499-504. Epub 2014 Dec 24.

Department of Maxillofacial surgery, Stomatology Clinic, Tartu University, Tartu, Estonia.

Objective: The aim of this study is to present and discuss the results of a European multicentre prospective study about pediatric maxillofacial trauma epidemiology during a year.

Study Design: The following data were recorded: gender, age, etiology, site of fracture, date of injury. Of the 3396 patients with maxillofacial fractures admitted within the study period, 114 (3.3%) were children aged 15 years and younger, with a male/female ratio of 2.6:1. Mean age was 10.9 years. Most patients (63%) were aged 11-15 years.

Results: The most frequent cause of injury was fall (36 patients). Sport injuries and assaults were almost limited to the oldest group, whereas falls were more uniformly distributed in the 3 groups. The most frequently observed fracture involved the mandible with 47 fractures. In particular, 18 condylar fractures were recorded, followed by 12 body fractures.

Conclusions: Falls can be acknowledged as the most important cause of facial trauma during the first years of life. The high incidence of sport accidents after 10 years may be a reason to increase the use of mouthguards and other protective equipment. Finally, the mandible (and in particular the condyle) was confirmed as the most frequent fracture site.
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http://dx.doi.org/10.1016/j.oooo.2014.12.012DOI Listing
May 2015

Giant canine with dentine anomalies in oculo-facio-cardio-dental syndrome.

J Craniomaxillofac Surg 2014 Jun 1;42(4):321-4. Epub 2013 Jul 1.

Service de Chirurgie Maxillo-Faciale et Stomatologie, Centre Hospitalier Universitaire Hôtel-Dieu, Nantes, France. Electronic address:

Radiculomegaly affecting incisors, canines or premolars is a rare radiological finding (Maden et al., 2010) but is pathognomomic of a rare x-linked dominant syndrome called oculo-facio-cardio-dental syndrome (OFCDS). As this syndrome includes cardiac malformations and can lead to blindness due to congenital glaucoma, oral and maxillofacial surgeons should be aware of the somatic anomalies potentially associated with radiculomegaly. We report a typical case of OFCDS and provide the first description of the microscopic dental anomalies associated with this syndrome.
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http://dx.doi.org/10.1016/j.jcms.2013.05.020DOI Listing
June 2014

Pertinence of a pre-colonoscopy consultation for routine information delivery.

Gastroenterol Clin Biol 2007 Dec;31(12):1055-61

Laboratoire de santé publique, Faculté de médecine, Marseille.

Aim Of The Study: The purpose of this study was to determine whether patients have a better level of information about colonoscopy and are more satisfied with medical care when they attend a dedicated consultation with a gastroenterologist prior to the procedure.

Methods: We conducted a prospective study which compared "exposed" (E) and "non exposed" (NE) patients. In group E, information about colonoscopy was delivered by a gastroenterologist during a special consultation at least 24 hours before the procedure. In group NE, information was delivered in the usual manner. The patients' level of information was measured after colonoscopy and 3 months later.

Results: Thirteen patients were included in group E and 18 in group NE. The level of information was better in group E, 5.2 +/- 2.1 versus 3.3 +/- 2.1 (P<0.04), as was satisfaction with medical care, 24.9 +/- 4.6 versus 23.0 +/- 5.1 (P<0.03). The differences in information levels remained at 3 months.

Conclusion: The information delivered during a dedicated precolonoscopy consultation increases assimilation of knowledge concerning the procedure and the patient's satisfaction with medical care.
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http://dx.doi.org/10.1016/s0399-8320(07)78334-3DOI Listing
December 2007