ABSTRACT: Autologous faecal microbiota transplantation to improve outcomes of haematopoietic stem cell transplantation - results of a single-centre feasibility study
Project description:Autologous nonmyeloablative hematopoietic stem cell transplantation (AHST) was the first therapeutic approaches that can improve beta cell function in type 1 diabetic (T1D) patients. This study was designed to investigate the potential mechanisms involved.We applied AHST to nine T1D patients diagnosed within six months and analyzed the acute response in peripheral blood genomic expression profiling at the six-month follow-up. Peripheral blood mononuclear of newly diagnosed type1 diabetes patients at diagnosis and at six months post-transplantation by autologous peripheral stem cell were purified by LymphoprepTm gradient purification according to the manufacturer's instructions (Axis-Shield PoC AS, Oslo, Norway) for futher microarray analysis.
Project description:In this randomised placebo-controlled trial, irritable bowel syndrome (IBS) patients were treated with faecal material from a healthy donor (n=8, allogenic FMT) or with their own faecal microbiota (n=8, autologous FMT). The faecal transplant was administered by whole colonoscopy into the caecum (30 g of stool in 150 ml sterile saline). Two weeks before the FMT (baseline) as well as two and eight weeks after the FMT, the participants underwent a sigmoidoscopy, and biopsies were collected at a standardised location (20-25 cm from the anal verge at the crossing with the arteria iliaca communis) from an uncleansed sigmoid. In patients treated with allogenic FMT, predominantly immune response-related genes sets were induced, with the strongest response two weeks after FMT. In patients treated with autologous FMT, predominantly metabolism-related gene sets were affected.
2019-10-14 | GSE138297 | GEO
Project description:Clinical results and microbiota changes after faecal microbiota transplantation for chronic pouchitis: a pilot study
Project description:<p><strong>BACKGROUND:</strong> Hematopoietic stem cell transplantation is a curative procedure for a variety of conditions. Despite major advances, a plethora of adverse clinical outcomes can develop post-transplantation including graft-versus-host disease and infections, which remain the major causes of morbidity and mortality. There is increasing evidence that the gastrointestinal microbiota is associated with clinical outcomes post-hematopoietic stem cell transplantation. Herein, we investigated the longitudinal dynamics of the gut microbiota and metabolome and potential associations to clinical outcomes in pediatric hematopoietic stem cell transplantation at a single centre.</p><p><strong>RESULTS:</strong> On admission (baseline), the majority of patients presented with a different gut microbial composition in comparison to healthy control children with a significantly lower alpha diversity. A further, marked decrease in alpha diversity was observed immediately post-transplantation and in most microbial diversity, and composition did not return to baseline status while hospitalized. Longitudinal trajectories identified continuous fluctuations in microbial composition, with the dominance of a single taxon in a significant proportion of patients. Using pam clustering, three clusters were observed in the dataset. Cluster 1 was common pre-transplantation, characterized by a higher abundance of <em>Clostridium XIVa</em>, <em>Bacteroides</em> and <em>Lachnospiraceae</em>; cluster 2 and cluster 3 were more common post-transplantation with higher abundance of <em>Streptococcus</em> and <em>Staphylococcus</em> in the former whilst <em>Enterococcus</em>, <em>Enterobacteriaceae</em> and <em>Escherichia</em> predominated in the latter. Cluster 3 was also associated with a higher risk of viraemia. Likewise, further multivariate analysis reveals <em>Enterobacteriaceae</em>, viraemia, use of total parenteral nutrition and various antimicrobials contributing towards cluster 3, <em>Streptococcaceae</em>, <em>Staphylococcaceae</em>, <em>Neisseriaceae</em>, vancomycin and metronidazole contributing towards cluster 2. <em>Lachnospiraceae</em>, <em>Ruminococcaceae</em>, <em>Bifidobacteriaceae</em> and not being on total parenteral nutrition contributed to cluster 1. Untargeted metabolomic analyses revealed changes that paralleled fluctuations in microbiota composition; importantly, low fecal butyrate was associated with higher risk of viraemia.</p><p><strong>CONCLUSIONS:</strong> These findings highlight the frequent shifts and dominations in the gut microbiota of pediatric patients undergoing hematopoietic stem cell transplantation. The study reveals associations between the fecal microbiota, metabolome and viraemia. To identify and explore the potential of microbial biomarkers that may predict risk of complications post-HSCT, larger multi-centre studies investigating longitudinal microbial profiling in pediatric hematopoietic stem cell transplantation are warranted.</p>
Project description:Transplantation of amniotic membrane-expanded limbal epithelium (AMLE) in place of donor tissue grafts results in significantly improved outcomes for patients suffering from severe limbal stem cell deficiency; however the reasons for such superior results are unclear. The purpose of this study was to identify transcriptional gene profiles specific to AMLE and donor central corneal epithelium (CE), which may contribute to the divergent clinical outcomes observed following transplant. Limbal fibroblasts which underlie the epithelium and secrete extracellular matrix proteins following injury/surgery were also profiled. Using cell culture, immunofluorescence, microarray gene expression profiling and qRT-PCR validation; this study aims to identify enriched biological processes and pathways which characterise AMLE and CE tissues. We hope the study outcomes will shed light onto the factors which contribute to provide the improved clinical outcomes associated with AMLE transplantation. Gene expression profiling of three central corneal buttons, three amniotic membrane-expanded limbal epithelial cultures and three limbal fibroblast cultures
Project description:Age-dependent changes of the gut-associated microbiome have been linked to increased frailty and systemic inflammation. This study found that age-associated changes of the gut microbiome of BALB/c and C57BL/6 mice could be reverted by co-housing of aged (22 months old) and adult (3 months old) mice for 30-40 days or faecal microbiota transplantation (FMT) from adult into aged mice. This was demonstrated using high-throughput sequencing of the V3-V4 hypervariable region of bacterial 16S rRNA gene isolated from faecal pellets collected from 3-4 months old adult and 22-23 months old aged mice before and after co-housing or FMT.
Project description:Background: T cells expressing antigen-specific chimeric antigen receptors (CARs) improve outcomes for CD19-expressing B-cell malignancies. We provide the first human application of T cells genetically modified using the Sleeping Beauty (SB) transposon/transposase system to express a CD19-specific CAR. Methods: T cells were genetically modified using DNA plasmids from the SB platform to stably express a second-generation CD19-specific CAR and selectively propagated ex vivo with activating and propagating cells (AaPC) and cytokines. Twenty-six patients with advanced NHL and ALL safely underwent hematopoietic stem-cell transplantation (HSCT) and infusion of CAR T cells as adjuvant therapy in the autologous (n=7) or allogeneic settings (n=19). Results: SB-mediated genetic transposition and stimulation resulted in 2,200-2,500-fold ex vivo genetically modified T-cell expansion, with 84% CAR expression, and without integration hotspots. The 30-month progression-free and overall survivals were 83% and 100%, respectively, following autologous HSCT, and the respective 12-month rates after allogeneic HSCT were 53% and 63%. No acute or late toxicities and no exacerbation of graft-versus-host-disease were observed. Despite a low antigen burden and unsupportive recipient cytokine environment, CAR T cells persisted for an average of 201 days for autologous and 51 days for allogeneic recipients. Conclusions: CD19-specific CAR T cells generated with SB and AaPC platforms were safe, and may provide additional cancer control as planned infusions after HSCT, supporting further clinical development of this non-viral gene therapy approach.
Project description:Autologous fat grafting (AFG), although an appealing approach to repair soft tissue defects, has various complications. Excessive inflammation at the transplant site is one of the main reasons for the poor effect of fat transplantation and occurrence of complications. Our previous study proved that Salvia miltiorrhiza can enhance fat graft survival. Salvianolic acid B (Sal-B) is the most abundant and bioactive water-soluble compound in Salvia miltiorrhiza and has anti-inflammatory effects on other diseases. Therefore, we hypothesized that salvianolic acid B could improve the effect of fat grafts by inhibiting inflammation.
Project description:We assessed the feasibility of transplanting a sheet of retinal pigment epithelial (RPE) cells differentiated from induced pluripotent stem cells (iPSCs) in a patient with neovascular age-related macular degeneration. The iPSCs were generated from skin fibroblasts obtained from two patients with advanced neovascular age-related macular degeneration and were differentiated into RPE cells. The RPE cells and the iPSCs from which they were derived were subject to extensive testing. A surgery that included the removal of the neovascular membrane and transplantation of the autologous iPSC-derived RPE cell sheet under the retina was performed in one of the patients.