Transplanted Hematopoietic Stem Cells from Bone Marrow Differentiate into Neural Lineage Cells and Promote Functional Recovery after Spinal Cord Injury in Mice

Abstract

Recovery in central nervous system disorders is hindered by the limited ability of the vertebrate central nervous system to regenerate lost cells, replace damaged myelin, and re-establish functional neural connections. Cell transplantation to repair central nervous system disorders is an active area of research, with the goal of reducing functional deficits. Recent animal studies showed that cells of the hematopoietic stem cell (HSC) fraction of bone marrow transdifferentiated into various nonhematopoietic cell lineages. We employed a mouse model of spinal cord injury and directly transplanted HSCs into the spinal cord 1 week after injury. We evaluated functional recovery using the hindlimb motor function score weekly for 5 weeks after transplantation. The data demonstrated a significant improvement in the functional outcome of mice transplanted with hematopoietic stem cells compared with control mice in which only medium was injected. Fluorescent in situ hybridization for the Y chromosome and double immunohistochemistry showed that transplanted cells survived 5 weeks after transplantation and expressed specific markers for astrocytes, oligodendrocytes, and neural precursors, but not for neurons. These results suggest that transplantation of HSCs from bone marrow is an effective strategy for the treatment of spinal cord injury.

Hematopoietic Stem Cells Reduce Postischemic Inflammation and Ameliorate Ischemic Brain Injury

“…Whereas transplantation of hematopoietic stem and precursor cells led to engraftment of microglia-like cell types within the healthy central nervous system, 27,28 direct injection of selected (Sca-1 ϩ Thy-1 ϩ c-kit ϩ ) HSCs in a model of spinal cord injury resulted in cell expression of markers typical of astrocytes, oligodendrocytes, and neural precursors. 31 In our model of experimental cerebral ischemia, Lin-Ϫ HSCs showed a macrophage or microglia-like phenotype after central nervous system entry at 72 hours after transplantation, and DNA-indices of GFP ϩ cells indicated absence of cell fusion events. However, transdifferentiation into neuronal or astrocytic cell types cannot be excluded to occur at later time points.…”

Localized Delivery of Brain-Derived Neurotrophic Factor-Expressing Mesenchymal Stem Cells Enhances Functional Recovery following Cervical Spinal Cord Injury

“…It is likely that incorporation of MSCs into neural tissue was limited, consistent with previous reports. 36,75,76 Other studies have evaluated markers of MSCs differentiation (e.g., CD90, CD105, CD45, or CD34) 77 or markers of neural, oligodendrocyte, or astrocytic phenotype 36 to determine cell fate following stem cell transplantation. However, such characterization would not enhance this study.…”

Rosiglitazone promotes development of a novel adipocyte population from bone marrow–derived circulating progenitor cells

“…CD45 + c-kit + cells are known to traffic from the BM and enter the peripheral circulation and can differentiate into cells with endothelial (25), smooth muscle (26), and neuronal (27) phenotypes. However, to our knowledge, these cells have not been shown to acquire adipocyte characteristics.…”