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Mesenchymal stromal cells improve the transplantation outcome of CRISPR-Cas9 gene-edited human HSPCs.

ABSTRACT: Mesenchymal stromal cells improve the transplantation outcome of CRISPR-Cas9 gene-edited human HSPCs.

PROVIDER: PRJNA852583 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13956785_1.fastq.gz	Fastqsanger.gz
	SRR13956785_2.fastq.gz	Fastqsanger.gz
	SRR13956786_1.fastq.gz	Fastqsanger.gz
	SRR13956786_2.fastq.gz	Fastqsanger.gz
	SRR13956787_1.fastq.gz	Fastqsanger.gz

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Mesenchymal stromal cells improve the transplantation outcome of CRISPR-Cas9 gene-edited human HSPCs (NHEJ)

Project description:Mesenchymal Stromal Cells (MSCs) have been employed in vitro to support HSPC expansion and in vivo to promote Hematopoietic Stem and Progenitor Cells (HSPCs) engraftment. Based on these studies, we developed an MSC-based co-culture system to optimize transplantation outcome of CRISPR-Cas9 gene-edited (GE) human HSPCs. We show that bone marrow (BM)-MSCs produce several hematopoietic supportive and anti-inflammatory factors capable to alleviate the proliferation arrest and mitigate the apoptotic and inflammatory programs activated in GE-HSPCs, improving their expansion and clonogenic potential in vitro. The use of BM-MSCs resulted in superior human engraftment and increased clonal output of GE-HSPCs contributing to the early phase of hematological reconstitution in the peripheral blood of transplanted mice. In conclusion, our work poses the biological bases for a novel clinical use of BM-MSCs to promote engraftment of GE-HSPCs and improve their transplantation outcome.

2022-09-01 | GSE206902 | GEO

Mesenchymal stromal cells improve the transplantation outcome of CRISPR-Cas9 gene-edited human HSPCs (RNA-seq)

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Mesenchymal stromal cells improve the transplantation outcome of CRISPR-Cas9 gene-edited human HSPCs (BAR-Seq)

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Mesenchymal stromal cells improve the transplantation outcome of CRISPR-Cas9 gene-edited human HSPCs (NHEJ)

Project description:Mesenchymal stromal cells improve the transplantation outcome of CRISPR-Cas9 gene-edited human HSPCs (NHEJ)

| PRJNA852586 | ENA

Mesenchymal stromal cells improve the transplantation outcome of CRISPR-Cas9 gene-edited human HSPCs (BAR-Seq)

Project description:Mesenchymal stromal cells improve the transplantation outcome of CRISPR-Cas9 gene-edited human HSPCs (BAR-Seq)

| PRJNA852574 | ENA

Mesenchymal stromal cells improve the transplantation outcome of CRISPR-Cas9 gene-edited human HSPCs (RNA-seq)

Project description:Mesenchymal stromal cells improve the transplantation outcome of CRISPR-Cas9 gene-edited human HSPCs (RNA-seq)

| PRJNA714119 | ENA

Mesenchymal stromal cells improve the transplantation outcome of CRISPR-Cas9 gene-edited human HSPCs.

Project description:Mesenchymal stromal cells (MSCs) have been employed in vitro to support hematopoietic stem and progenitor cell (HSPC) expansion and in vivo to promote HSPC engraftment. Based on these studies, we developed an MSC-based co-culture system to optimize the transplantation outcome of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 gene-edited (GE) human HSPCs. We show that bone marrow (BM)-MSCs produce several hematopoietic supportive and anti-inflammatory factors capable of alleviating the proliferation arrest and mitigating the apoptotic and inflammatory programs activated in GE-HSPCs, improving their expansion and clonogenic potential in vitro. The use of BM-MSCs resulted in superior human engraftment and increased clonal output of GE-HSPCs contributing to the early phase of hematological reconstitution in the peripheral blood of transplanted mice. In conclusion, our work poses the biological bases for a novel clinical use of BM-MSCs to promote engraftment of GE-HSPCs and improve their transplantation outcome.

| S-EPMC9840125 | biostudies-literature

Mesenchymal stromal cells improve the transplantation outcome of CRISPR-Cas9 gene-edited human HSPCs.

Project description: Not available

| S-EPMC9552814 | biostudies-literature

Mesenchymal stromal cells improve the transplantation outcome of CRISPR-Cas9 gene-edited human HSPCs.

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-09-01 | GSE206904 | GEO

CRISPR-edited human ES-derived oligodendrocyte progenitor cells improve remyelination in rodents

Project description:In Multiple Sclerosis (MS), inflammatory demyelinated lesions in the brain and spinal cord lead to neurodegeneration and progressive disability. Remyelination can restore fast saltatory conduction and neuroprotection but is inefficient in MS especially with increasing age, and is not yet improvable with therapies. Intrinsic and extrinsic inhibition of oligodendrocyte progenitor cell (OPC) function contributes to remyelination failure, and we hypothesised that the transplantation of ‘improved’ OPCs, genetically edited to overcome these obstacles, could improve remyelination. Here, we edited human(h) embryonic stem cell-derived OPCs to be unresponsive to a chemorepellent released from chronic MS lesions, and transplanted them into rodent models of chronic lesions. Edited hOPCs displayed enhanced migration and remyelination compared to controls, regardless of the host age and length of time post-transplant. This study demonstrates that genetic manipulation and transplantation of hOPCs overcomes the negative environment inhibiting remyelination, with translational implications for therapeutic strategies for people with progressive MS.

2023-08-23 | GSE241451 | GEO

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