Morphological response of stroke-injured brain to delivery of umbilical cord blood cells. (A) Occlusive stroke results in the degeneration of brain tissue supplied by the occluded vessel, which produces a lesion cavity. The lesion cavity compromises the cerebral cortex and lies some distance from a neurogenic region, the SVZ. The major fiber tracts forming the corpus callosum lie between the lesion cavity and the SVZ, a putative source of newly generated neurons observed in response to stem cell therapy. (B) Delivery of umbilical cord blood cells enriched with the CD34⁺ cell fraction to the tail vein results in circulation of these primitive stem cells throughout the body’s vascular system. (C) The circulating CD34⁺ cord blood cells in vessels adjacent to regions of neurodegeneration provide a possible supply of a number of cytokines and growth factors, including FGF-2 and IGF, that are proposed to cross into brain parenchyma directly or to stimulate local environmental production of growth factors. (D) Factors released by the circulating CD34⁺ cells also serve to recruit angioblasts, leading to angiogenesis. (E) Following CD34⁺ cord blood cell delivery, new cells are born and express neuronal lineage markers in a process called neurogenesis. In addition to being present in tissue remaining after the lesion, these new neurons contribute to restored tissue in the margin of the lesion cavity, which results in a small lesion cavity. It remains to be determined whether the newly generated neurons migrated from the neurogenic SVZ or were recruited from quiescent neural progenitor or stem cells residing in the parenchyma closer to the lesion cavity. Figure adapted with permission from Current Opinion in Neurobiology (16).