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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

Immunohistochemistry for HLA-A2 with hematoxylin counterstaining. (A) HLA-A2–positive cells accumulate in the cerebral cortex (brown cells within the circle). (B) HLA-A2–positive cells with ramified morphology (arrows). (C) A round HLA-A2–positive cell around a vessel (arrow). HLA-A2–positive cells with a round or ring morphology in the C5 lesion of the spinal cord at lower magnification (D) and at higher magnification (E). Scale bar = 100 μm.
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Figure 1: Immunohistochemistry for HLA-A2 with hematoxylin counterstaining. (A) HLA-A2–positive cells accumulate in the cerebral cortex (brown cells within the circle). (B) HLA-A2–positive cells with ramified morphology (arrows). (C) A round HLA-A2–positive cell around a vessel (arrow). HLA-A2–positive cells with a round or ring morphology in the C5 lesion of the spinal cord at lower magnification (D) and at higher magnification (E). Scale bar = 100 μm.

Mentions: To study the migration of donor-derived cells into the patient’s brain, we performed immunohistochemistry with anti–HLA-A2 antibody, which could distinguish donor-derived cells from host cells. Interestingly, donor-derived HLA-A2–positive cells were found in the cortex and around vessels (Figs. 1A–C). HLA-A2–positive cells often seemed to have accumulated in cortical regions (Fig. 1A); very few were observed in the deep white matter. Invading HLA-A2–positive cells in the cortical region had a ramified morphology similar to that of microglia (Fig. 1B). By contrast, immunohistochemical staining of the C5 lesion with anti–HLA-A2 antibodies showed more HLA-A2–positive cells in the parenchyma (Figs. 1D, E). Moreover, HLA-A2–positive cells in that area were round or ring-shaped but did not have a ramified morphology (Figs. 1D, E).


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)

Immunohistochemistry for HLA-A2 with hematoxylin counterstaining. (A) HLA-A2–positive cells accumulate in the cerebral cortex (brown cells within the circle). (B) HLA-A2–positive cells with ramified morphology (arrows). (C) A round HLA-A2–positive cell around a vessel (arrow). HLA-A2–positive cells with a round or ring morphology in the C5 lesion of the spinal cord at lower magnification (D) and at higher magnification (E). Scale bar = 100 μm.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Immunohistochemistry for HLA-A2 with hematoxylin counterstaining. (A) HLA-A2–positive cells accumulate in the cerebral cortex (brown cells within the circle). (B) HLA-A2–positive cells with ramified morphology (arrows). (C) A round HLA-A2–positive cell around a vessel (arrow). HLA-A2–positive cells with a round or ring morphology in the C5 lesion of the spinal cord at lower magnification (D) and at higher magnification (E). Scale bar = 100 μm.
Mentions: To study the migration of donor-derived cells into the patient’s brain, we performed immunohistochemistry with anti–HLA-A2 antibody, which could distinguish donor-derived cells from host cells. Interestingly, donor-derived HLA-A2–positive cells were found in the cortex and around vessels (Figs. 1A–C). HLA-A2–positive cells often seemed to have accumulated in cortical regions (Fig. 1A); very few were observed in the deep white matter. Invading HLA-A2–positive cells in the cortical region had a ramified morphology similar to that of microglia (Fig. 1B). By contrast, immunohistochemical staining of the C5 lesion with anti–HLA-A2 antibodies showed more HLA-A2–positive cells in the parenchyma (Figs. 1D, E). Moreover, HLA-A2–positive cells in that area were round or ring-shaped but did not have a ramified morphology (Figs. 1D, E).

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