Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains

TLDR

Stem cells are valuable for disease treatment, but limited access to brain-derived stem cells restricts their utility. The study aimed to determine whether bone marrow–derived marrow stromal cells could adopt neural fates when injected into neonatal mouse brains. MSCs were injected into the lateral ventricle of neonatal mice and monitored for migration and differentiation within the brain microenvironment. MSCs migrated throughout the forebrain and cerebellum, differentiated into astrocytes in the striatum and hippocampus, populated neuron‑rich regions, and some donor cells expressed neurofilament in the brain stem, indicating that MSCs can generate diverse neural lineages and may serve as vectors for CNS disorder therapies.

Abstract

Stem cells are a valuable resource for treating disease, but limited access to stem cells from tissues such as brain restricts their utility. Here, we injected marrow stromal cells (MSCs) into the lateral ventricle of neonatal mice and asked whether these multipotential mesenchymal progenitors from bone marrow can adopt neural cell fates when exposed to the brain microenvironment. By 12 days postinjection, MSCs migrated throughout the forebrain and cerebellum without disruption to the host brain architecture. Some MSCs within the striatum and the molecular layer of the hippocampus expressed glial fibrillary acidic protein and, therefore, differentiated into mature astrocytes. MSCs also populated neuron rich regions including the Islands of Calleja, the olfactory bulb, and the internal granular layer of the cerebellum. A large number of MSCs also were found within the external granular layer of the cerebellum. In addition, neurofilament positive donor cells were found within the reticular formation of the brain stem, suggesting that MSCs also may have differentiated into neurons. Therefore, MSCs are capable of producing differentiated progeny of a different dermal origin after implantation into neonatal mouse brains. These results suggest that MSCs are potentially useful as vectors for treating a variety of central nervous system disorders.