Enhanced Efficacy of Human Brain-Derived Neural Stem Cells by Transplantation of Cell Aggregates in a Rat Model of Parkinson's Disease

Abstract

ObjectiveNeural tissue transplantation has been a promising strategy for the treatment of Parkinson's disease (PD). However, transplantation has the disadvantages of low-cell survival and/or development of dyskinesia. Transplantation of cell aggregates has the potential to overcome these problems, because the cells can extend their axons into the host brain and establish synaptic connections with host neurons. In this present study, aggregates of human brain-derived neural stem cells (HB-NSC) were transplanted into a PD animal model and compared to previous report on transplantation of single-cell suspensions.MethodsRats received an injection of 6-OHDA into the right medial forebrain bundle to generate the PD model and followed by injections of PBS only, or HB-NSC aggregates in PBS into the ipsilateral striatum. Behavioral tests, multitracer (2-deoxy-2-[18F]-fluoro-D-glucose ([18F]-FDG) and [18F]-N-(3-fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl)nortropane ([18F]-FP-CIT) microPET scans, as well as immunohistochemical (IHC) and immunofluorescent (IF) staining were conducted to evaluate the results.ResultsThe stepping test showed significant improvement of contralateral forelimb control in the HB-NSC group from 6-10 weeks compared to the control group (p<0.05). [18F]-FP-CIT microPET at 10 weeks posttransplantation demonstrated a significant increase in uptake in the HB-NSC group compared to pretransplantation (p<0.05). In IHC and IF staining, tyrosine hydroxylase and human β2 microglobulin (a human cell marker) positive cells were visualized at the transplant site.ConclusionThese results suggest that the HB-NSC aggregates can survive in the striatum and exert therapeutic effects in a PD model by secreting dopamine.

Engraftment of Dopamine Neuron Precursor Cells Derived from Adult Mesenchymal Stem Cells: Preliminary In Vivo Study

“…Immunodetection of MSCs transplanted into rat brains: Three weeks after cell transplantation into the brain, rats were sacrificed and the brains were obtained for immunohistological analysis. 7 Results confirmed cell engraftment in the brain at the MFB, without migration of the transplanted cells to different areas (Figure 3). Apomorphine-induced rotational behavior: Rat rotational behavior was determined 4 and 5weeks after the induction of a Parkinsonian lesion by means of a 6-OHDA injection.…”

“…Transplantation of neural cell aggregates as well as dopaminergic neurons derived from embryonic stem cells in PD animal models have proved to possess potential in improving behavioral tests and cell grafting. 7,8 However obtaining of human brain neural stem cells for transplantation may limit this procedure as potential therapy. Additionally, the use of embryonic stem cells faces ethical concerns with limitation for their use.…”

The Effect of MSCs Derived from the Human Umbilical Cord Transduced by Fibroblast Growth Factor‐20 on Parkinson’s Disease

“…Every mouse was monitored for 3 times with interval of 30 mins, and the average was then calculated. According to the literature [ 14 , 15 ], in the open field test, successful establishment of mouse model of PD was verified as the number of rearing instances was less than 15 times/5 min and that of ambulation instances was less than 55 times/5 min, with less than 30 seconds of latency and more than 20 times/2 mins of drop frequency in the rota rod test. Five weeks later, after accidental death of mice was excluded, the total number of mice that met the criteria stated above was 50.…”