Targeting myeloid cells to the brain using non-myeloablative conditioning.

Bone marrow-derived cells (BMDCs) are able to colonize the central nervous system (CNS) at sites of damage. This ability makes BMDCs an ideal cellular vehicle for transferring therapeutic genes/molecules to the CNS. However, conditioning is required for bone marrow-derived myeloid cells to engraft i...

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Autores principales:	Chotima Böttcher, Francisco Fernández-Klett, Nadine Gladow, Simone Rolfes, Josef Priller
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/67571b8b4dea43199c3a189ebe3841b5
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spelling	oai:doaj.org-article:67571b8b4dea43199c3a189ebe3841b52021-11-18T08:47:50ZTargeting myeloid cells to the brain using non-myeloablative conditioning.1932-620310.1371/journal.pone.0080260https://doaj.org/article/67571b8b4dea43199c3a189ebe3841b52013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24244666/?tool=EBIhttps://doaj.org/toc/1932-6203Bone marrow-derived cells (BMDCs) are able to colonize the central nervous system (CNS) at sites of damage. This ability makes BMDCs an ideal cellular vehicle for transferring therapeutic genes/molecules to the CNS. However, conditioning is required for bone marrow-derived myeloid cells to engraft in the brain, which so far has been achieved by total body irradiation (TBI) and by chemotherapy (e.g. busulfan treatment). Unfortunately, both regimens massively disturb the host's hematopoietic compartment. Here, we established a conditioning protocol to target myeloid cells to sites of brain damage in mice using non-myeloablative focal head irradiation (HI). This treatment was associated with comparatively low inflammatory responses in the CNS despite cranial radiation doses which are identical to TBI, as revealed by gene expression analysis of cytokines/chemokines such as CCL2, CXCL10, TNF-α and CCL5. HI prior to bone marrow transplantation resulted in much lower levels of blood chimerism defined as the percentage of donor-derived cells in peripheral blood (< 5%) compared with TBI (> 95%) or busulfan treatment (> 50%). Nevertheless, HI effectively recruited myeloid cells to the area of motoneuron degeneration in the brainstem within 7 days after facial nerve axotomy. In contrast, no donor-derived cells were detected in the lesioned facial nucleus of busulfan-treated animals up to 2 weeks after transplantation. Our findings suggest that myeloid cells can be targeted to sites of brain damage even in the presence of very low levels of peripheral blood chimerism. We established a novel non-myeloablative conditioning protocol with minimal disturbance of the host's hematopoietic system for targeting BMDCs specifically to areas of pathology in the brain.Chotima BöttcherFrancisco Fernández-KlettNadine GladowSimone RolfesJosef PrillerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e80260 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chotima Böttcher Francisco Fernández-Klett Nadine Gladow Simone Rolfes Josef Priller Targeting myeloid cells to the brain using non-myeloablative conditioning.
description	Bone marrow-derived cells (BMDCs) are able to colonize the central nervous system (CNS) at sites of damage. This ability makes BMDCs an ideal cellular vehicle for transferring therapeutic genes/molecules to the CNS. However, conditioning is required for bone marrow-derived myeloid cells to engraft in the brain, which so far has been achieved by total body irradiation (TBI) and by chemotherapy (e.g. busulfan treatment). Unfortunately, both regimens massively disturb the host's hematopoietic compartment. Here, we established a conditioning protocol to target myeloid cells to sites of brain damage in mice using non-myeloablative focal head irradiation (HI). This treatment was associated with comparatively low inflammatory responses in the CNS despite cranial radiation doses which are identical to TBI, as revealed by gene expression analysis of cytokines/chemokines such as CCL2, CXCL10, TNF-α and CCL5. HI prior to bone marrow transplantation resulted in much lower levels of blood chimerism defined as the percentage of donor-derived cells in peripheral blood (< 5%) compared with TBI (> 95%) or busulfan treatment (> 50%). Nevertheless, HI effectively recruited myeloid cells to the area of motoneuron degeneration in the brainstem within 7 days after facial nerve axotomy. In contrast, no donor-derived cells were detected in the lesioned facial nucleus of busulfan-treated animals up to 2 weeks after transplantation. Our findings suggest that myeloid cells can be targeted to sites of brain damage even in the presence of very low levels of peripheral blood chimerism. We established a novel non-myeloablative conditioning protocol with minimal disturbance of the host's hematopoietic system for targeting BMDCs specifically to areas of pathology in the brain.
format	article
author	Chotima Böttcher Francisco Fernández-Klett Nadine Gladow Simone Rolfes Josef Priller
author_facet	Chotima Böttcher Francisco Fernández-Klett Nadine Gladow Simone Rolfes Josef Priller
author_sort	Chotima Böttcher
title	Targeting myeloid cells to the brain using non-myeloablative conditioning.
title_short	Targeting myeloid cells to the brain using non-myeloablative conditioning.
title_full	Targeting myeloid cells to the brain using non-myeloablative conditioning.
title_fullStr	Targeting myeloid cells to the brain using non-myeloablative conditioning.
title_full_unstemmed	Targeting myeloid cells to the brain using non-myeloablative conditioning.
title_sort	targeting myeloid cells to the brain using non-myeloablative conditioning.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/67571b8b4dea43199c3a189ebe3841b5
work_keys_str_mv	AT chotimabottcher targetingmyeloidcellstothebrainusingnonmyeloablativeconditioning AT franciscofernandezklett targetingmyeloidcellstothebrainusingnonmyeloablativeconditioning AT nadinegladow targetingmyeloidcellstothebrainusingnonmyeloablativeconditioning AT simonerolfes targetingmyeloidcellstothebrainusingnonmyeloablativeconditioning AT josefpriller targetingmyeloidcellstothebrainusingnonmyeloablativeconditioning
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Targeting myeloid cells to the brain using non-myeloablative conditioning.

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