Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice

Abstract

Glial cells are thought to derive embryologically from either myeloid cells of the hematopoietic system (microglia) or neuroepithelial progenitor cells (astroglia and oligodendrocytes). However, it is unclear whether the glia in adult brains free of disease or injury originate solely from cells present in the brain since the fetal stage of development, or if there is further input into such adult brains from cells originating outside the central nervous system. To test the ability of hematopoietic cells to contribute to the central nervous system, we have transplanted adult female mice with donor bone marrow cells genetically marked either with a retroviral tag or by using male donor cells. Using in situ hybridization histochemistry, a continuing inf lux of hematopoietic cells into the brain was detected. Marrow-derived cells were already detected in the brains of mice 3 days after transplant, and their numbers increased over the next several weeks, exceeding 14,000 cells per brain in several animals. Marrow-derived cells were widely distributed throughout the brain, including the cortex, hippocampus, thalamus, brain stem, and cerebellum. When in situ hybridization histochemistry was combined with immunohistochemical staining using lineage-specific markers, some bone marrow-derived cells were positive for the microglial antigenic marker F4͞80. Other marrow-derived cells surprisingly expressed the astroglial marker glial fibrillary acidic protein. These results indicate that some microglia and astroglia arise from a precursor that is a normal constituent of adult bone marrow.

The origin and differentiation of microglial cells during development

“…This second possibility challenges the idea that astrocytes are of neuroectodermal lineage, but agrees with the ®nding by Eglitis and Mezey (1997) that astrocytes of donor origin appear in mice subjected to bone marrow grafting.…”

“…A study by Krall et al (1994) showed that ca 20% of microglial cells (mainly perivascular cells) were replaced by cells of donor origin 6±8 months after bone marrow transplant in mice; these results were in accordance with those reported by Kennedy and Abkowitz (1997). Finally, a recent paper (Eglitis and Mezey, 1997) con®rmed that transplant-derived cells colonize the CNS of bone marrow-chimeric mice; certain of the cells of donor origin were identi®ed as microglia, but surprisingly, some astrocytes were also found to be of donor origin.…”

Human Bone Marrow Stem Cells Exhibit Neural Phenotypes and Ameliorate Neurological Deficits after Grafting into the Ischemic Brain of Rats

“…Bone marrow stromal cells or mesenchymal stem cells (MSCs) not only give rise to mesodermal lineage cells such as osteoblasts, chondrocytes, adipocytes, and muscle cells (4,13,29,55,33), but also adopt neuroectodermal cell fate. It has been shown that donor-derived neurons and astrocytes are found in host rodent brain following transplantation of rodent bone marrow (8,14,29,35). However, it is not known if transplantation of MSCs into the brain can be beneficial in treating neurological disorders.…”

Human reserve pluripotent mesenchymal stem cells are present in the connective tissues of skeletal muscle and dermis derived from fetal, adult, and geriatric donors

“…By contrast, other studies have shown that stem cells residing in one tissue can differentiate into cell types of another tissue. For example, reserve stem cells derived from bone marrow can differentiate into neurons and glia (Eglitis and Mezey, 1997;Kopen et al, 1999), restore dystrophin expression in skeletal muscle (Gussoni et al, 1999), serve as a source of hepatic oval cells (Petersen et al, 1999), provide cells for neovascularization (Asahara et al, 1999;Kalka et al, 2000), and restore cartilage, bone, and fat (Pittenger et al, 1999;Prokop, 1997;Yoo et al, 1998). Conversely, stem cells derived from neural tissues (Bjornson et al, 1999) and muscle tissues (Jackson et al, 1999) can differentiate into blood.…”