Cord blood-derived stem cells administered intravenously to newborn rats can engraft in brain and skin lesions and produce neuronal or epithelial progenitor cells

摘要

CD133(+) cells isolated from umbilical cord blood (UCB) represent an established source of transplantable hematopoietic progenitors, and subpopulations of such cells have been shown to be capable of differentiating into mesenchymal lineages. Here we investigated whether CD133(+) UCB cells may contribute to the regeneration of injured brain and skin regions. A purified population of CD133(+) cells from human UCB was expanded in a stem cell medium, labeled with a fluorescent cell tracker and administered intravenously to 9-day-old rats subjected to unilateral carotid artery ligation and subsequent hypoxia (8% O2) for 120 minutes on day 7 after birth. The capability of these cells to differentiate into the neurogenic lineage was confirmed in vitro by RT-PCR and immunostaining of differentiation markers including NeuN and MAP2B. Their biodistribution in vivo was investigated by fluorescence microscopy and immunostaining of human nuclear antigen. Cell differentiation in vivo was assessed histologically and immunohistochemically using various markers. Animals which received a cell-free buffer and sham-operated animals treated with the stem cells served as controls. In caspase-3-positive brain lesions of all rats subjected to hypoxic-ischemic injury, numerous labeled cells were detected that expressed human nuclear antigen and CXCR4. Overlapping staining of NeuN and MAP2B revealed neurogenic differentiation of the transplanted cells. Furthermore, in the wounded jugular skin of all rats subjected to hypoxic-ischemic brain damage or sham-operation abundant human cells were detectable at the site of injury. Human cells located around the epidermal basement membrane and hair follicle bulges were positive for CD133 and epidermal differentiation markers, whereas CD133(-) human cells were found in the dermal connective tissue. Thus, UCB-derived stem cells can be mobilized from blood vessels into brain and skin lesions, where they may contribute to tissue regeneration.