Transplantation of a Novel Human Cord Blood-Derived Neural-Like Stem Cell Line in a Rat Model of Cortical Infarct

Abstract

Umbilical cord blood can be a rich source of stem/progenitor cells, not only for hematopoetic but also for other tissue-specific lineages. Recently, we have developed a novel, self-renewed neural-like stem cell line named HUCB-NSC from human cord blood. To test if HUCB-NSCs can supply brain in need of regeneration, we injected these cells into immunosuppressed intact rat forebrain and to animals suffering from a photothrombotic cortical lesion at 48 h after injury. The survival, migration, and differentiation of the transplanted HUCB-NSCs were measured at 7 and 30 days post-transplantation by immunohistochemical methods. Results show survival and extensive migration of transplanted neural-like progenitors into damaged brain cortex during the first week of post-stroke recovery. The donor cells accumulated mainly in peri-infarct area and then differentiated showing a strong co-expression of neuronal (NF-200) but only moderate of astrocytic (GFAP) cell markers. However, the paucity of HUCB-NSCs detected within post-ischemic rat brain at the end of a 1 month period, as well as acute rejection of grafted cells by intact, yet cyclosporin A (CsA) immunosuppressed, rat brain tissue, suggests development of a severe adverse host reaction to the presence of alien donor cells and an urgent need for further study of the immunological response evoked by xenotransplantations of human cord blood-derived cells in animal experimental models.

A novel, neural potential of non-hematopoietic human umbilical cord blood stem cells

“…Seven days after transplantation high number of these cells exhibited neuronal phenotypes (NF-200) and, to lower extend, glial (GFAP, S-100β) cell markers. Some of these cells survived for 4 weeks; however most of them disappeared during this time, despite of employed CsA immunosuppression (Kozlowska et al, 2007). These results agree with other reports where only a few transplanted HUCB cells were found in injured CNS at 4-6 weeks after transplantation (Liu et al, 2006;Kuh et al, 2005).…”

Future of cord blood for non-oncology uses

“…In vitro by RT-PCR, alizarin red and von Kossa-staining, ALP detection, immunohistochemistry and western blot 8,31,[110][111][112][113] In vitro by safranin-O staining, RT-PCR and immunohistochemistry 8,31 In vitro by immunohistochemistry, RT-PCR, calcium imaging and western blot [114][115][116][117] In vivo in parkinsonian rat model, ischemic rat model [118][119][120][121][122][123] In vitro by immunohistochemistry, RT-PCR, PAS-staining, urea and albumin production, western blot and LDL uptake 31,94,124,125 CD34/AC133-positive (hematopoietic progenitor) cells In vitro by RT-PCR 126 In vivo in NOD/SCID mouse model 95,96 Not defined cells from MNC In vitro by immunohistochemistry, whole-cell patch-clamp, western blot and RT-PCR [127][128][129][130][131] In vivo in spinal cord injury and intra-brain injection in rat and NOD/SCID mouse model 73,76,[80][81][82][83][84][86][87][88][89][90][91][92]<...>…”

Cord Blood as a Treatment for Stroke

“…In subsequent studies, few UCB cells have been found to survive in the brain of stroked rats or mice. Even in studies that have used UCB derived cells that have undergone neural induction prior to transplantation into infarcted cortex, there was a paucity of cells (Kozłowska et al 2007). …”