Intrastriatal Grafting of Chromospheres: Survival and Functional Effects in the 6-OHDA Rat Model of Parkinson's Disease

Abstract

Cell replacement therapy in Parkinson’s disease (PD) aims at re-establishing dopamine neurotransmission in the striatum by grafting dopamine-releasing cells. Chromaffin cell (CC) grafts produce some transitory improvements of functional motor deficits in PD animal models, and have the advantage of allowing autologous transplantation. However, CC grafts have exhibited low survival, poor functional effects and dopamine release compared to other cell types. Recently, chromaffin progenitor-like cells were isolated from bovine and human adult adrenal medulla. Under low-attachment conditions, these cells aggregate and grow as spheres, named chromospheres. Here, we found that bovine-derived chromosphere-cell cultures exhibit a greater fraction of cells with a dopaminergic phenotype and higher dopamine release than CC. Chromospheres grafted in a rat model of PD survived in 57% of the total grafted animals. Behavioral tests showed that surviving chromosphere cells induce a reduction in motor alterations for at least 3 months after grafting. Finally, we found that compared with CC, chromosphere grafts survive more and produce more robust and consistent motor improvements. However, further experiments would be necessary to determine whether the functional benefits induced by chromosphere grafts can be improved, and also to elucidate the mechanisms underlying the functional effects of the grafts.

Dendrobium nobileLindl alkaloid attenuates 6‐OHDA‐induced dopamine neurotoxicity

“…However, DNLA increased the time stay on rotarod test and the number of DA neurons. These findings were in accordance with previous research reported that 6-OHDA (8-12 μg/rat) induces movement disorder as main symptom of PD by decreasing the number of DA neurons in SNpc [26,27].…”

Adrenal cortical and chromaffin stem cells: Is there a common progeny related to stress adaptation?

“…Due to their favorable properties, chromospheres could represent a new and promising source for cell replacement therapy in Parkinson´s disease as a significantly higher population of chromospherederived cells has been shown to acquire a dopaminergic phenotype compared to chromaffin cells (Boronat-Garcia et al, 2016;Vukicevic et al, 2012).…”

Human embryonic stem cells overexpressing dopaminergic transcription factors survive and differentiate in the substantia nigra in vivo

“…To measure dopaminergic imbalance, animals were injected intraperitoneally with 4 mg/kg amphetamine (Sigma-Aldrich). The number of turns was recorded for 90 min using a custom-made computerized image and motion recognition system [24]. Animals were evaluated two weeks after injury, and only those with more than 400 ipsilateral turns were selected for transplantation procedures.…”

“…Immuno uorescence assays were performed as previously described [24]. Brain slices were rinsed three times in PBS/0.3% Triton X-100 (Sigma-Aldrich), treated with antigen retriever in citrate buffer (BioSB) at 65°C for 30 min, and washed three times with PBS.…”