Anna Gosiewska

Cells Isolated from Umbilical Cord Tissue Rescue Photoreceptors and Visual Functions in a Rodent Model of Retinal Disease

Progressive photoreceptor degeneration resulting from genetic and other factors is a leading and largely untreatable cause of blindness worldwide. The object of this study was to find a cell type that is effective in slowing the progress of such degeneration in an animal model of human retinal disease, is safe, and could be generated in sufficient numbers for clinical application. We have compared efficacy of four human‐derived cell types in preserving photoreceptor integrity and visual functions after injection into the subretinal space of the Royal College of Surgeons rat early in the progress of degeneration. Umbilical tissue‐derived cells, placenta‐derived cells, and mesenchymal stem cells were studied; dermal fibroblasts served as cell controls. At various ages up to 100 days, electroretinogram responses, spatial acuity, and luminance threshold were measured. Both umbilical‐derived and mesenchymal cells significantly reduced the degree of functional deterioration in each test. The effect of placental cells was not much better than controls. Umbilical tissue‐derived cells gave large areas of photoreceptor rescue; mesenchymal stem cells gave only localized rescue. Fibroblasts gave sham levels of rescue. Donor cells were confined to the subretinal space. There was no evidence of cell differentiation into neurons, of tumor formation or other untoward pathology. Since the umbilical tissue‐derived cells demonstrated the best photoreceptor rescue and, unlike mesenchymal stem cells, were capable of sustained population doublings without karyotypic changes, it is proposed that they may provide utility as a cell source for the treatment of retinal degenerative diseases such as retinitis pigmentosa.

Delayed administration of human umbilical tissue-derived cells improved neurological functional recovery in a rodent model of focal ischemia.

Background and Purpose— The short time window required by neuroprotective strategies for successful treatment of patients with ischemic stroke precludes treatment for most. However, clinical therapies based on neuroregeneration might extend this therapeutic time window and thus address a significant unmet need. Human umbilical tissue-derived cells have shown great potential as neuroregenerative candidates for stroke treatment. Methods— The effectiveness of intravenous administration of human umbilical tissue-derived cells was tested in a rodent middle cerebral artery stroke model in a dose escalation study (doses tested: 3×105, 1×106, 3×x106, or 1×107 cells/injection) followed by a time-of-administration study (time after stroke: Day 1, Day 7, Day 30, and Day 90 at a dose of 5×106 cells/injection). Controls were phosphate-buffered saline injections and human bone marrow-derived mesenchymal stromal cell injections. Post-treatment outcome tools included the modified neurological severity score and the adhesive removal tests. Histology was performed on all cases to evaluate synaptogenesis, neurogenesis, angiogenesis, and cell apoptosis. Results— Statistically significant improvements of human umbilical tissue-derived cell treatment versus phosphate-buffered saline in modified neurological severity scores and adhesive test results were observed for doses ≥3×106 cells up to 30 days poststroke. At doses ≥3×106, histological evaluations confirmed enhanced synaptogenesis, vessel density, and reduced apoptosis in the ischemic boundary zone and increased proliferation of progenitor cells in the subventricular zone of human umbilical tissue-derived cell-treated animals versus phosphate-buffered saline controls. Conclusions— These results indicate effectiveness of intravenous administration of human umbilical tissue-derived cells in a rodent stroke model compared with phosphate-buffered saline control and warrant further investigation for possible use in humans.