There is now evidence to suggest that bone marrow mesenchymal stem cells (MSCs) not only differentiate into mesodermal cells, but can also adopt the fate of endodermal and ectodermal cell types. In this study, we addressed the hypotheses that human MSCs can differentiate into neural cells when implanted in the brain and restore sensorimotor function after experimental stroke. Purified human MSCs were grafted into the cortex surrounding the area of infarction 1 week after cortical brain ischemia in rats. Two and 6 weeks after transplantation animals were assessed for sensorimotor function and then sacrificed for histological examination. Ischemic rats that received human MSCs exhibited significantly improved functional performance in limb placement test. Histological analyses revealed that transplanted human MSCs expressed markers for astrocytes (GFAP+), oligodendroglia (GalC+), and neurons (βIII+, NF160+, NF200+, hNSE+, and hNF70+). The morphological features of the grafted cells, however, were spherical in nature with few processes. Therefore, it is unlikely that the functional recovery observed by the ischemic rats with human MSC grafts was mediated by the integration of new "neuronal" cells into the circuitry of the host brain. The observed functional improvement might have been mediated by proteins secreted by transplanted hMSCs, which could have upregulated host brain plasticity in response to experimental stroke.
Bibliographical noteFunding Information:
We thank Bruce Lindgren from Division of Biostatistics, University of Minnesota, for his assistance with the statistical analyses, Linda Linnerud for her administrative assistance, and Anna Abt and Jonggul Kim for their technical assistance. This work was supported by the Lyle French Neurosurgery Research Fund, Children’s Cancer Research Fund, Univ. of Minnesota Bone Marrow Transplant Research Fund, the Leukemia Society of America, and NIH Grants 1F31AI/GM10291, 1F30MH12157, and R01-NS-40831.
- Bone marrow
- Brain ischemia
- Middle cerebral artery occlusion
- Stem cell