Perivascular, but not parenchymal, cerebral engraftment of donor cells after non-myeloablative bone marrow transplantation.
Exp Mol Pathol
; 95(1): 7-17, 2013 Aug.
Article
em En
| MEDLINE
| ID: mdl-23567123
ABSTRACT
Myeloablative (MyA) bone marrow transplantation (BMT) results in robust engraftment of BMT-derived cells in the central nervous system (CNS) and is neuroprotective in diverse experimental models of neurodegenerative diseases of the brain and retina. However, MyA irradiation is associated with significant morbidity and mortality and does not represent a viable therapeutic option for the elderly. Non-myeloablative (NMyA) BMT is less toxic, but it is not known if the therapeutic efficacy observed with MyA BMT is preserved. As a first step to address this important gap in knowledge, we evaluated and compared engraftment characteristics of BMT-derived monocytes/microglia using several clinically relevant NMyA pretransplant conditioning regimens in C57BL/6 mice. These included chemotherapy (fludarabine and cyclophosphamide) with or without 2 Gy irradiation, and 5.5 Gy irradiation alone. Each regimen was followed by transplantation of whole bone marrow from green fluorescent protein-expressing wild type (wt) mice. While stable hematopoietic engraftment occurred, to varying degrees, in all NMyA regimens, only 5.5 Gy irradiation resulted in significant engraftment of BMT-derived cells in the brain, where these cells were exclusively localized to perivascular, leptomeningeal, and related anatomic regions. Engraftment in retina under 5.5 Gy NMyA conditions was significantly reduced compared to MyA, but robust engraftment was identified in the optic nerve. Advancing the therapeutic applications of BMT to neurodegenerative diseases will require identification of the barrier mechanisms that MyA, but not NMyA, BMT is able to overcome.
Palavras-chave
AD; ALS; ANOVA; Alzheimer's disease; BMT; Bone marrow transplantation; CNS; Central nervous system; GCL; GFP; Gray; Gy; HBSS; Hank's Balanced Salt Solution; IPL; Irradiation; Microglia; MyA; NMyA; Non-myeloablative; OPL; PBS; amyotrophic lateral sclerosis; analysis of variance; bone marrow transplant; central nervous system; ganglion cell layer; green fluorescent protein; inner plexiform layer; myeloablative; non-myeloablative; outer plexiform layer; phosphate buffered saline; wild type; wt
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sistema Nervoso Central
/
Transplante de Medula Óssea
/
Condicionamento Pré-Transplante
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article