Laboratory of Endocrinology and Genomics, CHUL Research Center and Department of Molecular Medicine, Faculty of Medicine, Laval University, Québec, Canada.
Cell Transplant. 2012;21(6):1149-59. doi: 10.3727/096368911X593154. Epub 2011 Sep 22.
Understanding how bone marrow-derived cells (BMDCs) enter the central nervous system (CNS) is critical for the development of therapies for brain-related disorders using hematopoietic stem cells. We investigated the brain damages and blood-brain barrier (BBB) modification following either whole-body irradiation or a myeloablative chemotherapy regimen in mice, and the capacity for these treatments to induce the entry of BMDCs into the CNS. Neither treatment had a lasting effect on brain integrity and both were equally efficient at achieving myeloablation. Injection of bone marrow cells from green fluorescent protein (GFP) transgenic mice was able to completely repopulate the hematopoietic niche in the circulation and in hematopoietic organs (thymus and spleen). However, GFP(+) cells only entered the brain following whole-body irradiation. We conclude that myeloablation, damages to the brain integrity, or the BBB and peripheral chimerism are not responsible for the entry of BMDCs into the CNS following irradiation.
了解骨髓来源的细胞（BMDCs）如何进入中枢神经系统（CNS）对于使用造血干细胞治疗与大脑相关的疾病的疗法的发展至关重要。我们研究了全身照射或骨髓清除化疗方案在小鼠中引起的脑损伤和血脑屏障（BBB）改变，以及这些治疗诱导 BMDC 进入 CNS 的能力。两种治疗都对脑完整性没有持久影响，并且在实现骨髓清除方面同样有效。从绿色荧光蛋白（GFP）转基因小鼠注射骨髓细胞能够完全重新填充循环和造血器官（胸腺和脾脏）中的造血龛位。然而，只有在全身照射后 GFP(+)细胞才进入大脑。我们得出结论，骨髓清除、脑完整性损伤或 BBB 和外周嵌合不是照射后 BMDC 进入 CNS 的原因。
