Intravenous versus intrastriatal cord blood administration in a rodent model of stroke

Abstract

Human umbilical cord blood (hUCB) is a rich source of hematopoietic stem cells that have been used to reconstitute immune cells and blood lineages. Cells from another hematopoietic source, bone marrow, have been found to differentiate into neural cells and are effective in the treatment of stroke. In this study, we administered hUCB cells intravenously into the femoral vein or directly into the striatum and assessed which route of cell administration produced the greatest behavioral recovery in rats with permanent middle cerebral artery occlusion (MCAO). All animals were immunosuppressed with cyclosporine (CSA). When spontaneous activity was measured using the Digiscan automated system, it was found to be significantly less when hUCB was transplanted 24 hr after stroke compared with nontransplanted, stroked animals (P < 0.01). Furthermore, behavioral recovery was similar with both striatal and femoral hUCB delivery. This is in contrast to the step test, in which significant improvements were found only after femoral delivery of the hUCB cells. In the passive avoidance test, transplanted animals learned the task faster than nontransplanted animals (P < 0.05). Together, these results suggest that hUCB transplantation may be an effective treatment for brain injuries, such as stroke, or neurodegenerative disorders. In addition, intravenous delivery may be more effective than striatal delivery in producing long-term functional benefits to the stroked animal.

Rescuing the neonatal brain from hypoxic injury with autologous cord blood

“…[89][90][91][92][93][94][95][96] Beneficial effects have generally been observed determined by behavioral improvements in most cases, but also by the reduction in lesion size in some studies. Owing to the poor survival of the transplanted cells and little evidence for neural differentiation, bystander effects have been postulated to be the main mechanisms for functional recovery after CB transplantation, including release of neurotrophic factors to stimulate endogenous neurogenesis, prevention of cell loss and immunomodulation (Figure 4).…”

Bone marrow-derived mesenchymal stromal cells for the repair of central nervous system injury

“…MSCs can also be isolated from other sources such as adipose tissue, umbilical cord blood and mobilized peripheral blood, and have also been used in transplant studies, [31][32][33][34][35] although yields from the latter two are extremely low. Transplantation of MSCs for CNS repair was first reported in 2000 by Chen et al, 36 after administration of bone marrow with brain-derived neurotrophic factor (BDNF) into a model of middle cerebral artery occlusion (MCAo).…”

Long-term cultured human umbilical cord neural-like cells transplanted into the striatum of NOD SCID mice

“…When transplanted into the neurogenic region of neonatal rat brain, a small fraction of these cells migrate and express neuronal and astroglial proteins [46]. Further, when intravenously transplanted into the rat middle cerebral artery occlusion stroke model, behavioral deficits were reduced [43]. However, transplantation of HUCB cells into adult or aged rat brains was associated with vigorous rejection and strong immunosuppression was required to protect the graft [42].…”