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

ABSTRACT:

SUBMITTER: Crippa S

PROVIDER: S-EPMC9552814 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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

Crippa Stefania S Conti Anastasia A Vavassori Valentina V Ferrari Samuele S Beretta Stefano S Rivis Silvia S Bosotti Roberto R Scala Serena S Pirroni Stefania S Jofra-Hernandez Raisa R Santi Ludovica L Basso-Ricci Luca L Merelli Ivan I Genovese Pietro P Aiuti Alessandro A Naldini Luigi L Di Micco Raffaella R Bernardo Maria Ester ME

Molecular therapy : the journal of the American Society of Gene Therapy 20220911 10

PMID: 36096132

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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.

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

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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.

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