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Differentiation of Donor-Derived Cells Into Microglia After Umbilical Cord Blood Stem Cell Transplantation.

Takahashi K, Kakuda Y, Munemoto S, Yamazaki H, Nozaki I, Yamada M - J. Neuropathol. Exp. Neurol. (2015)

Bottom Line: Peripheral cell invasion of the brain parenchyma can only occur with disruption of the blood-brain barrier.Although the blood-brain barrier and glia limitans seemed to prevent invasion of these donor-derived cells, most of the invading donor-derived ramified cells were maintained in the cerebral cortex.This result suggests that invasion of donor-derived cells occurs through the pial membrane.

View Article: PubMed Central - PubMed

Affiliation: From the Department of Neurology, National Hospital Organization Iou Hospital (KT); Departments of Neurology and Neurobiology of Aging (KT, YK, IN, MY) and Cellular Transplantation Biology (SM, HY), Kanazawa University Graduate School of Medical Science; and Department of Internal Medicine, Keijyu Kanazawa Hospital (SM), Kanazawa, Japan.

ABSTRACT
Recent studies have indicated that microglia originate from immature progenitors in the yolk sac. After birth, microglial populations are maintained under normal conditions via self-renewal without the need to recruit monocyte-derived microglial precursors. Peripheral cell invasion of the brain parenchyma can only occur with disruption of the blood-brain barrier. Here, we report an autopsy case of an umbilical cord blood transplant recipient in whom cells derived from the donor blood differentiated into ramified microglia in the recipient brain parenchyma. Although the blood-brain barrier and glia limitans seemed to prevent invasion of these donor-derived cells, most of the invading donor-derived ramified cells were maintained in the cerebral cortex. This result suggests that invasion of donor-derived cells occurs through the pial membrane.

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Related in: MedlinePlus

Double staining of donor-derived cells by immunohistochemistry. (A) Double staining of donor-derived cells with anti–HLA-A2 antibody (brown) and anti-CCR2 antibody (blue). Arrows indicate CCR2-negative and HLA-A2–positive cells; arrowheads indicate double-positive cells. (B) Migrated HLA-A2–positive cells were counted in 3 independent sections; the frequency of CCR2-positive cells and CCR2-negative cells is shown in the bar graph. Bars indicate mean ± SD. (C) Double staining of donor-derived cells with anti–HLA-A2 antibody (brown) and anti-CX3CR1 antibody (blue). Arrow indicates a double-positive cell indicating donor origin; arrowhead indicates a CX3CR1-positive and HLA-A2–negative cell indicating host origin.
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Figure 3: Double staining of donor-derived cells by immunohistochemistry. (A) Double staining of donor-derived cells with anti–HLA-A2 antibody (brown) and anti-CCR2 antibody (blue). Arrows indicate CCR2-negative and HLA-A2–positive cells; arrowheads indicate double-positive cells. (B) Migrated HLA-A2–positive cells were counted in 3 independent sections; the frequency of CCR2-positive cells and CCR2-negative cells is shown in the bar graph. Bars indicate mean ± SD. (C) Double staining of donor-derived cells with anti–HLA-A2 antibody (brown) and anti-CX3CR1 antibody (blue). Arrow indicates a double-positive cell indicating donor origin; arrowhead indicates a CX3CR1-positive and HLA-A2–negative cell indicating host origin.

Mentions: Because CCR2 and CX3CR1 are very important for distinguishing resident microglia from monocyte-originating microglia-like cells, we next explored the expression of CCR2 and CX3CR1 in HLA-A2–positive cells. Approximately 60% of HLA-A2–positive cells were CCR2-negative, and most of the invading HLA-A2–positive cells were CX3CR1-positive (Figs. 3A–C).


Differentiation of Donor-Derived Cells Into Microglia After Umbilical Cord Blood Stem Cell Transplantation.

Takahashi K, Kakuda Y, Munemoto S, Yamazaki H, Nozaki I, Yamada M - J. Neuropathol. Exp. Neurol. (2015)

Double staining of donor-derived cells by immunohistochemistry. (A) Double staining of donor-derived cells with anti–HLA-A2 antibody (brown) and anti-CCR2 antibody (blue). Arrows indicate CCR2-negative and HLA-A2–positive cells; arrowheads indicate double-positive cells. (B) Migrated HLA-A2–positive cells were counted in 3 independent sections; the frequency of CCR2-positive cells and CCR2-negative cells is shown in the bar graph. Bars indicate mean ± SD. (C) Double staining of donor-derived cells with anti–HLA-A2 antibody (brown) and anti-CX3CR1 antibody (blue). Arrow indicates a double-positive cell indicating donor origin; arrowhead indicates a CX3CR1-positive and HLA-A2–negative cell indicating host origin.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4554226&req=5

Figure 3: Double staining of donor-derived cells by immunohistochemistry. (A) Double staining of donor-derived cells with anti–HLA-A2 antibody (brown) and anti-CCR2 antibody (blue). Arrows indicate CCR2-negative and HLA-A2–positive cells; arrowheads indicate double-positive cells. (B) Migrated HLA-A2–positive cells were counted in 3 independent sections; the frequency of CCR2-positive cells and CCR2-negative cells is shown in the bar graph. Bars indicate mean ± SD. (C) Double staining of donor-derived cells with anti–HLA-A2 antibody (brown) and anti-CX3CR1 antibody (blue). Arrow indicates a double-positive cell indicating donor origin; arrowhead indicates a CX3CR1-positive and HLA-A2–negative cell indicating host origin.
Mentions: Because CCR2 and CX3CR1 are very important for distinguishing resident microglia from monocyte-originating microglia-like cells, we next explored the expression of CCR2 and CX3CR1 in HLA-A2–positive cells. Approximately 60% of HLA-A2–positive cells were CCR2-negative, and most of the invading HLA-A2–positive cells were CX3CR1-positive (Figs. 3A–C).

Bottom Line: Peripheral cell invasion of the brain parenchyma can only occur with disruption of the blood-brain barrier.Although the blood-brain barrier and glia limitans seemed to prevent invasion of these donor-derived cells, most of the invading donor-derived ramified cells were maintained in the cerebral cortex.This result suggests that invasion of donor-derived cells occurs through the pial membrane.

View Article: PubMed Central - PubMed

Affiliation: From the Department of Neurology, National Hospital Organization Iou Hospital (KT); Departments of Neurology and Neurobiology of Aging (KT, YK, IN, MY) and Cellular Transplantation Biology (SM, HY), Kanazawa University Graduate School of Medical Science; and Department of Internal Medicine, Keijyu Kanazawa Hospital (SM), Kanazawa, Japan.

ABSTRACT
Recent studies have indicated that microglia originate from immature progenitors in the yolk sac. After birth, microglial populations are maintained under normal conditions via self-renewal without the need to recruit monocyte-derived microglial precursors. Peripheral cell invasion of the brain parenchyma can only occur with disruption of the blood-brain barrier. Here, we report an autopsy case of an umbilical cord blood transplant recipient in whom cells derived from the donor blood differentiated into ramified microglia in the recipient brain parenchyma. Although the blood-brain barrier and glia limitans seemed to prevent invasion of these donor-derived cells, most of the invading donor-derived ramified cells were maintained in the cerebral cortex. This result suggests that invasion of donor-derived cells occurs through the pial membrane.

Show MeSH
Related in: MedlinePlus