Therapeutic efficacy of intracerebral hematopoietic stem cell gene therapy in an Alzheimer’s disease mouse model

The conditions supporting the generation of microglia-like cells in the central nervous system (CNS) after transplantation of hematopoietic stem/progenitor cells (HSPC) have been studied to advance the treatment of neurodegenerative disorders. Here, we explored the transplantation efficacy of different cell subsets and delivery routes with the goal of favoring the establishment of a stable and exclusive engraftment of HSPCs and their progeny in the CNS of female mice. In this setting, we show that the CNS environment drives the expansion, distribution and myeloid differentiation of the locally transplanted cells towards a microglia-like phenotype. Intra-CNS transplantation of HSPCs engineered to overexpress TREM2 decreased neuroinflammation, Aβ aggregation and improved memory in 5xFAD female mice. Our proof of concept study demonstrates the therapeutic potential of HSPC gene therapy for Alzheimer's disease.

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Publication Details

Journal
Nature Communications
Published
2024-09-13
DOI
https://doi.org/10.1038/s41467-024-52301-w
Citations
10
Primary Topic
Neurogenesis and neuroplasticity mechanisms
Type
article
Field-Weighted Citation Impact
4.11
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article

Therapeutic efficacy of intracerebral hematopoietic stem cell gene therapy in an Alzheimer’s disease mouse model

Alessandra Biffi, Francesca Ferro, Alessia Capotondo, Paolo Cabras et al.
10 citations
Nature Communications
Neurogenesis and neuroplasticity mechanisms
4.11
article

Therapeutic efficacy of intracerebral hematopoietic stem cell gene therapy in an Alzheimer’s disease mouse model

Alessandra Biffi, Francesca Ferro, Alessia Capotondo, Paolo Cabras, Pietro Rigoni, Marco Peviani, Eleonora Cavalca, Danilo Pellin, Rita Milazzo, Annita Montepeloso, Rajesh Kumar, Sabyasachi Das, Yuri Ciervo
article en
10 citations

Abstract

The conditions supporting the generation of microglia-like cells in the central nervous system (CNS) after transplantation of hematopoietic stem/progenitor cells (HSPC) have been studied to advance the treatment of neurodegenerative disorders. Here, we explored the transplantation efficacy of different cell subsets and delivery routes with the goal of favoring the establishment of a stable and exclusive engraftment of HSPCs and their progeny in the CNS of female mice. In this setting, we show that the CNS environment drives the expansion, distribution and myeloid differentiation of the locally transplanted cells towards a microglia-like phenotype. Intra-CNS transplantation of HSPCs engineered to overexpress TREM2 decreased neuroinflammation, Aβ aggregation and improved memory in 5xFAD female mice. Our proof of concept study demonstrates the therapeutic potential of HSPC gene therapy for Alzheimer's disease.

Nature CommunicationsVol. 15(1)
University of Padua (IT), University of Pavia (IT), The San Raffaele Telethon Institute for Gene Therapy (IT), Dana-Farber/Boston Children's Cancer and Blood Disorders Center (US)
Openalex Percentile: Top 6%
Neurogenesis and neuroplasticity mechanisms
4.11
DOIOpen Access PDFOpenAlex
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