Genetically modified macrophages accelerate myelin repair
Abstract: Preventing neurodegeneration‐associated disability progression in patients with multiple sclerosis (MS) remains an unmet therapeutic need. As remyelination prevents axonal degeneration, promoting this process in patients might enhance neuroprotection. In demyelinating mouse lesions, local overexpression of semaphorin 3F (Sema3F), an oligodendrocyte progenitor cell (OPC) attractant, increases remyelination. However, molecular targeting to MS lesions is a challenge. A clinically relevant paradigm for delivering Sema3F to demyelinating lesions could be to use blood‐derived macrophages as vehicles. Thus, we chose transplantation of genetically modified hematopoietic stem cells (HSCs) as means of obtaining chimeric mice with circulating Sema3F‐overexpressing monocytes. We demonstrated that Sema3F‐transduced HSCs stimulate OPC migration in a neuropilin 2 (Nrp2, Sema3F receptor)‐dependent fashion, which was conserved in middle‐aged OPCs. While demyelinating lesions induced in mice with Sema3F‐expressing blood cells showed no changes in inflammation and OPC survival, OPC recruitment was enhanced which accelerated the onset of remyelination. Our results provide a proof of concept that blood cells, particularly monocytes/macrophages, can be used to deliver pro‐remyelinating agents “at the right time and place,” suggesting novel means for remyelination‐promoting strategies in MS.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Genetically modified macrophages accelerate myelin repair ; day:13 ; month:07 ; year:2022 ; extent:17
EMBO molecular medicine / European Molecular Biology Organization ; (13.07.2022) (gesamt 17)
- Creator
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Aigrot, Marie‐Stéphane
Barthelemy, Clara
Moyon, Sarah
Dufayet‐Chaffaud, Gaelle
Izagirre‐Urizar, Leire
Gillet‐Legrand, Beatrix
Tada, Satoru
Bayón‐Cordero, Laura
Chara, Juan‐Carlos
Matute, Carlos
Cartier, Nathalie
Lubetzki, Catherine
Tepavčević, Vanja
- DOI
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10.15252/emmm.202114759
- URN
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urn:nbn:de:101:1-2022071315104724101096
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:21 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Aigrot, Marie‐Stéphane
- Barthelemy, Clara
- Moyon, Sarah
- Dufayet‐Chaffaud, Gaelle
- Izagirre‐Urizar, Leire
- Gillet‐Legrand, Beatrix
- Tada, Satoru
- Bayón‐Cordero, Laura
- Chara, Juan‐Carlos
- Matute, Carlos
- Cartier, Nathalie
- Lubetzki, Catherine
- Tepavčević, Vanja
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Myelin down-regulates myelin phagocytosis by microglia and macrophages through interactions between CD47 on myelin and SIRPα (signal regulatory protein-α) on phagocytes
Deletion of CD47 from Schwann cells and macrophages hastens myelin disruption/dismantling and scavenging in Schwann cells and augments myelin debris phagocytosis in macrophages
Interplay between androgen and CXCR4 chemokine signaling in myelin repair
CD36-mediated uptake of myelin debris by macrophages and microglia reduces neuroinflammation
Transplantation of myelin-forming cells to repair the injured spinal cord
BTK inhibition limits microglia-perpetuated CNS inflammation and promotes myelin repair
The tumor suppressor protein merlin regulates myelin phagocytosis in Schwann cells and macrophages
Acid sphingomyelinase deficiency blocks chronic experimental autoimmune encephalomyelitis and improves myelin repair
Correction to: Interplay between androgen and CXCR4 chemokine signaling in myelin repair
Myelin-phagocytosing macrophages modulate autoreactive T cell proliferation
Teriflunomide as a therapeutic means for myelin repair
Myelin alters the inflammatory phenotype of macrophages by activating PPARs
Myelin down-regulates myelin phagocytosis by microglia and macrophages through interactions between CD47 on myelin and SIRPα (signal regulatory protein-α) on phagocytes
Deletion of CD47 from Schwann cells and macrophages hastens myelin disruption/dismantling and scavenging in Schwann cells and augments myelin debris phagocytosis in macrophages
Interplay between androgen and CXCR4 chemokine signaling in myelin repair
CD36-mediated uptake of myelin debris by macrophages and microglia reduces neuroinflammation
Transplantation of myelin-forming cells to repair the injured spinal cord
BTK inhibition limits microglia-perpetuated CNS inflammation and promotes myelin repair
The tumor suppressor protein merlin regulates myelin phagocytosis in Schwann cells and macrophages
Acid sphingomyelinase deficiency blocks chronic experimental autoimmune encephalomyelitis and improves myelin repair
Correction to: Interplay between androgen and CXCR4 chemokine signaling in myelin repair
Myelin-phagocytosing macrophages modulate autoreactive T cell proliferation
Teriflunomide as a therapeutic means for myelin repair
Myelin alters the inflammatory phenotype of macrophages by activating PPARs
Myelin down-regulates myelin phagocytosis by microglia and macrophages through interactions between CD47 on myelin and SIRPα (signal regulatory protein-α) on phagocytes
Deletion of CD47 from Schwann cells and macrophages hastens myelin disruption/dismantling and scavenging in Schwann cells and augments myelin debris phagocytosis in macrophages
Interplay between androgen and CXCR4 chemokine signaling in myelin repair
CD36-mediated uptake of myelin debris by macrophages and microglia reduces neuroinflammation
Transplantation of myelin-forming cells to repair the injured spinal cord
BTK inhibition limits microglia-perpetuated CNS inflammation and promotes myelin repair
The tumor suppressor protein merlin regulates myelin phagocytosis in Schwann cells and macrophages
Acid sphingomyelinase deficiency blocks chronic experimental autoimmune encephalomyelitis and improves myelin repair