Autologous Muscle Cells Research Articles

Iltamiocel Autologous Cell Therapy for the Treatment of Female Stress Urinary Incontinence: A Double-Blind, Randomized, Stratified, Placebo-Controlled Trial.

This study aimed to determine the efficacy and safety of iltamiocel investigational autologous muscle cell therapy in females with stress urinary incontinence (SUI). Adult females were randomized 2:1 to iltamiocel (150 × 106 cells) or placebo and stratified by severity and prior SUI surgery. The primary objective was efficacy based on the frequency of stress incontinence episodes (SIE) recorded in a 3-day diary at 12 months posttreatment. After 12 months, placebo participants could elect to receive open-label iltamiocel. Efficacy and safety analyses were performed using all patients as treated populations. The study enrolled 311 patients, 297 were randomized to either iltamiocel (n = 199) or placebo (n = 98). Of the 295 participants that completed 12 months blinded follow-up, the proportion achieving the primary endpoint of ≥ 50% SIE reduction was not statistically different between treatment groups (52% vs. 53.6%; p = 0.798). A significantly greater proportion of iltamiocel participants in the prior SUI surgery stratum group achieved ≥ 75% SIE reduction compared with placebo, (40% vs. 16%; p = 0.037). Treatment response was maintained at 24 months in 78.4% and 64.9% of iltamiocel participants who achieved ≥ 50% and ≥ 75% SIE reduction, respectively, at Month 12. Adverse events related to the treatment were reported in 19 (9.5%) iltamiocel participants and 6 (6.1%) placebo participants. The study did not meet its primary endpoint however, iltamiocel cell therapy is safe and may be ideally suited to female patients who have undergone prior surgery for SUI. Additional study in this group of patients with high unmet medical needs is warranted. ClinicalTrials.gov identifier: NCT01893138; EudraCT number: 2014-002919-41.

FRI0521 Cd28null T Cells Kill Autologous Muscle Cells from Polymyositis Patients in Vitro by Perforin-Dependent Mechanisms

BackgroundInflammatory infiltrates of muscles in polymyositis are dominated by CD4+CD28null and CD8+CD28null T cells1. In contrast to conventional CD28+ T cells, these cells have a restricted T cell-receptor repertoire, rapidly...

SAT0021 CD28null T cells from myositis patients are cytotoxic to autologous muscle cells in vitro

BackgroundT cells are implicated in the disease pathogenesis of dermatomyositis (DM) and polymyositis (PM) but their specificity and effector functions in the inflamed muscle remain unclear. We have previously demonstrated...

Integration of collagen matrices into the urethra when implanted as onlay graft

To assess the integration of decellularized heterologous collagen matrices into the urethra, when implanted with no cells or when seeded with autologous smooth muscle cells. Eighteen New Zealand rabbits were randomly assigned to two groups: Group I (n = 9) - animals undergoing urethral segment resection with interposition of a patch of heterologous collagen matrix seeded with autologous smooth muscle cells; Group II (n = 9) - animals undergoing resection of a urethral segment with interposition of a decellularized heterologous collagen matrix patch. Two animals from each group were sacrificed on postoperative days seven, fourteen and twenty-eight; three animals from each group were sacrificed at the end of three postoperative months. At the end of the third month one animal from each group underwent urethroscopy for urethral integrity assessment and one animal from each group had its microcirculation image captured by a SDF device (Side-stream Dark Field - Microscan Analysis Software). One animal from each group in each euthanasia period underwent cystourethrography so as the urethra could be viewed at flow time. The matrices integration was assessed through histological examination using hematoxylin and eosin (H & E), Masson trichrome (MT), Picrosirius red and Von Willebrand staining. In a blind study with two pathologists all the slides were studied. The matrices whether seeded or not with autologous muscle cells were able to restore the architecture of the urethra, but were eliminated from the first week on, before incorporation. Microcirculation of the neourethra, at the end of the third month, showed the same characteristics as a normal urethra in both groups of animals. Natural heterologous matrices implanted in the urethra as onlay graft were not incorporated into its walls but were able to fully restore the cell architecture of the organ, regardless of being seeded or not with autologous muscle cells.

CD28null T cells from myositis patients are cytotoxic to autologous muscle cells in vitro

Background/purposeT cells are implicated in the disease pathogenesis of dermatomyositis (DM) and polymyositis (PM) but their specificity and effector functions in the inflamed muscle remain unclear. The authors have previously...

Tissue Remodeling in a Bioartifical Fibromuscular Patch Following Transplantation in a Human

Tissue engineering applications might help to overcome currently encountered limitations in reconstructive surgery in many surgical subspecialties (1). Recently we reported the successful reconstruction of a tracheobronchial defect in a patient using a bioartificial airway patch (2). Here we describe the remodeling of the transplanted bioartificial tissue. In a 58-year-old male, a bioartificial fibromuscular patch was implanted into a 1.5 × 1.5 cm large tracheobronchial anastomosis defect (onset 4 weeks postoperatively) as previously described in detail (2). Briefly, the patient had undergone right carinal pneumectomy for relapsing non–small-cell lung cancer following operation and radiation (60 Gy) 4 years earlier. The defect had caused pleural empyema and pyosepticemia which were treated by thoracostomy and medically. At time of patch implantation, an omentum major transposition and right subscapular myoplasty combined with a thoracoplasty were performed. The patch had been generated within 5 weeks from a 3 × 4 cm skin biopsy that was obtained at the thoracostomy site. Autologous muscle cells (MC) and fibroblasts (Fb) were isolated enzymatically from the biopsy and cultured for 2 weeks (37°C, HAM-F12/MEM culture media; volume ratio 50:50). An acellular 24 × 36 mm collagen network (derived from a porcine jejunal segment) served as carrier matrix. Autologous Fb and MC in a cell ratio of 95:5 were seeded for 3 weeks on the matrix (37°C, HAM-F12/MEM culture media; volume ratio 50:50). Patch integrity was controlled by fibroscopies 1, 3, 6, and 12 weeks following implantation. We detected patch matrix reorganization resulting in increased mechanical stability and a defect area decrease from 12 × 9 mm to 9 × 5 mm. A transtracheal patch biopsy performed 12 weeks after implantation documented a harmonic cellular distribution pattern with a surprisingly altered patch composition representing 80% MC and 20% Fb (Fig. 1).FIGURE 1.: Cellular patch composition. Overall cell number doubled within 3 months. Fb represented the cellular majority during tissue culture before implantation (in vitro). Three months after implantation tissue remodeling resulted in a dominant MC fraction.Numerous clinical and experimental studies surveyed bioartificial implants for a wide range of clinical applications, including tracheal reconstruction (1). As yet, the venture to generate a bioartificial tracheal substitute did not provide a convincing graft (3) and currently autologous repair tissues (i.e., pericardial patches) represent dependable alternatives for limited tracheal reconstruction that result in scar tissue formation and contraction of the airway defect (4). In our presented case, we repaired a limited defect in the tracheobronchial system with a tissue engineered autologous tracheal patch. Analogous to clinical experiences with autologous pericardial patches, we detected a decrease of defect size over time. In contrast to previous findings, patch biopsy revealed a profound change of tissue composition within the first 3 months following implantation: the MC:Fb cell ratio had reversed in favor of MC. This unexpected increase of smooth muscle cells in the patch matrix cannot be explained by cicatrization. The underlying mechanism, however, remains unknown and cannot be explained by our data. Either the privileged ingrowth of patient MC or a survival benefit of implanted MC could explain these findings. In the light of previous unexpected (sometimes fatal) clinical experiences with bioartificial grafts (5), further studies are needed to address questions regarding the healing behavior and mechanisms of bioartificial implants. Thorsten Walles Christian Biancosino Patrick Zardo Paolo Macchiarini Department of Thoracic and Vascular Surgery Heidehaus Hospital Hannover, Germany Jens Gottlieb Department of Pulmonology Medical School Hannover Hannover, Germany Heike Mertsching Fraunhofer Institute for Interfacial Engineering and Biotechnology Stuttgart, Germany

First human transplantation of a bioengineered airway tissue

First human transplantation of a bioengineered airway tissue

The role of cytokines in polymyositis. III. Recombinant human interferon-gamma enhances T cell adhesion to cultured human muscle cells.

To investigate the effect of interferon-gamma (IFN gamma) on the adhesive interactions between human peripheral blood T cells and human skeletal muscle cells at various stages of muscle cell differentiation and maturation in vitro. Human muscle cell cultures were established from normal muscle biopsy material, using the explant technique. T cells were studied for their capacity to adhere to IFN gamma-treated and untreated myoblasts and myotubes. The role of intercellular adhesion molecule type 1 (ICAM-1) in cell adhesion to muscle cells was examined in blocking studies, by enzyme-linked immunosorbent assay (ELISA), and by immunohistochemical staining using monoclonal antibodies (MAb). Treatment of muscle cells (myoblasts and myotubes) with IFN gamma resulted in a significant dose-dependent increase in the number of adherent T cells. Adhesion of T cells to muscle cells was significantly inhibited by MAb to ICAM-1 and to lymphocyte function-associated antigen type 1, but not by MAb to HLA-DR. There was no difference in the level of T cell adhesion to IFN gamma-treated allogeneic versus autologous muscle cells. By ELISA and immunohistochemical analysis, ICAM-1 expression on the surface of cultured human muscle cells was either absent or barely detectable, but was strongly induced by treatment of muscle cells with IFN gamma. Induction of cell adhesion molecules on muscle cells by IFN gamma may be an important mechanism for the localization of T cells in the affected muscles of patients with autoimmune myositis.

Coxsackievirus Aggregates in Muscle Cells of a Polymyositis Patient

Muscle biopsy specimens of a patient with polymyositis showed crystalline structures resembling picornavirus aggregates within muscle cells. The patient's serum reacted in an indirect immunofluorescence assay with autologous muscle cells. A strongly positive immunofluorescence staining was also noted when a section of muscle tissue was reacted with coxsackievirus A9 antiserum, and a weakly positive reaction was noted with coxsackievirus B2 antiserum. No staining was observed after treatment with antiserum to poliovirus type 1 or echovirus types 11 and 22.