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Myeloablation followed by autologous stem cell transplantation normalizes systemic sclerosis molecular signatures

ABSTRACT: Myeloablation followed by autologous stem cell transplantation normalizes systemic sclerosis molecular signatures

PROVIDER: PRJNA542097 | ENA |

REPOSITORIES: ENA

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Myeloablation followed by autologous stem cell transplantation normalizes systemic sclerosis molecular signatures

Project description:This is global gene expression study of whole blood samples collected in the Cyclophosphamide Or Transplantation (SCOT) randomized controlled trial, as well as unaffected controls. Patients with diffuse cutaneous systemic sclerosis (scleroderma) received either myeloablation followed by autologous stem cell transplantation or intravenous cyclophosphamide

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Myeloablation Followed by Hematopoietic Stem Cell Transplantation and Long-Term Normalization of Systemic Sclerosis Molecular Signatures

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Myeloablation followed by autologous stem cell transplantation normalises systemic sclerosis molecular signatures.

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Myeloablation Followed by Hematopoietic Stem Cell Transplantation and Long-Term Normalization of Systemic Sclerosis Molecular Signatures

Project description:Myeloablation Followed by Hematopoietic Stem Cell Transplantation and Long-Term Normalization of Systemic Sclerosis Molecular Signatures

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Longitudinal CITE-seq analysis in juvenile-onset systemic sclerosis monocytes following autologous stem cell transplant

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Longitudinal CITE-seq analysis in juvenile-onset systemic sclerosis monocytes following autologous stem cell transplant

Project description:Juvenile systemic sclerosis (jSSc) is a rare and severe autoimmune disease marked by skin fibrosis and damage to multiple organ systems. This study implements autologous stem cell transplantation (ASCT), a newly available treatment protocol which aims to restore immune homeostasis, in this case amongst jSSc patients. Here, we analyze peripheral blood mononuclear cells (PBMCs) from 3 jSSc patients prior to ASCT and 6, 12, and 24 months post treatment. These samples were then sequenced and tagged with antibodies using cellular indexing of transcriptomes and epitopes (CITE-seq). To analyze these samples and how they change over time, this study implements a newly designed generalized linear model. It was adopted from an established method with a coefficient for time since ASCT to identify numerous genes and pathways with downward longitudinal trends, many of which have previously been implicated in SSc development, and may help further understand disease pathogenesis. Our longitudinal differential gene expression analysis focused mainly on monocytes, which demonstrated strong downwards trends in multiple pathogenic genes/pathways. Specifically, nuclear factor-B (NFB)-driven inflammatory signaling was increased in jSSc monocytes at baseline compared to healthy controls, but decreased to match healthy monocyte levels over time following ASCT. We also note a sharp longitudinal reduction in jSSc monocyte expression of SERPINE1, a gene which has previously been implicated in SSc pathogenesis.This workflow describes immune reprogramming in three jSSc patients who underwent ASCT and introduces a statistically-justified framework for longitudinal single-cell modeling.

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Proteomic analysis of cerebrospinal fluid of amyotrophic lateral sclerosis patients in the presence of autologous bone marrow derived mesenchymal stem cells

Project description:Amyotrophic lateral sclerosis (ALS) is a fatal and rapidly progressive motoneuron degenerative disorder. There are still no drugs capable of slowing disease evolution or improving life quality of ALS patients. Thus, autologous stem cell therapy has emerged as an alternative treatment regime to be investigated in clinical ALS. Using Proteomics and Protein-Protein Interaction Network analyses combined with bioinformatics, the possible cellular mechanisms and molecular targets related to mesenchymal stem cells (MSCs, 1x10^6 cells/kg, intrathecally in the lumbar region of the spine) were investigated in cerebrospinal fluid (CSF) of ALS patients who received intrathecal infusions of autologous bone marrow-derived MSCs thirty days after cell therapy. Proteomics revealed 220 deregulated proteins in CSF of ALS subjects treated with MSCs compared to CSF collected from the same patients prior to MSCs infusion. Bioinformatics enriched analyses highlighted events of Extracellular matrix and Cell adhesion molecules as well as related key targets APOA1, APOE, APP, C4A, C5, FGA, FGB, FGG and PLG in the CSF of cell treated ALS subjects. Extracellular matrix and cell adhesion molecules as well as their related highlighted components have emerged as key targets of autologous MSCs in CSF of ALS patients.

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Autologous hematopoietic stem cell transplantation promotes connective tissue remodeling in systemic sclerosis patients.

Project description: Not available

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Autologous Hematopoietic Stem Cell Transplantation in Systemic Sclerosis: Current Evidence and Future Directions.

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