KA-bridged transplantation of mesencephalic tissue and olfactory ensheathing cells in a Parkinsonian rat model

Abstract

The pathology of Parkinson's disease (PD) results mainly from nigrostriatal pathway damage. Unfortunately, commonly used PD therapies do not repair the disconnected circuitry. It has been reported that using kainic acid (KA, an excitatory amino acid) in bridging transplantation may be useful to generate an artificial tract and reconstruct the nigrostriatal pathway in 6-hydroxydopamine (6-OHDA) lesioned rats. In this study, we used KA bridging and a co-graft of rat olfactory ensheathing cells (OECs) and rat E14 embryonic ventral mesencephalic (VM) tissue to restore the nigrostriatal pathway of the PD model rats. The methamphetamine-induced rotational behaviour, 4-[ F]-ADAM (a selectively serotonin transporter radioligand)/micro-PET imaging, and immunohistochemistry were used to assess the effects of the transplantation. At 9 weeks post-grafting in PD model rats, the results showed that the PD rats undergoing VM tissue and OECs co-grafts (VM-OECs) exhibited better motor recovery compared to the rats receiving VM tissue transplantation only. The striatal uptake of 4-[ F]-ADAM and tyrosine hydroxylase immunoreactivity (TH-ir) of the grafted area in the VM-OECs group were also more improved than those of the VM alone group. These results suggested that OECs may enhance the survival of the grafted VM tissue and facilitate the recovery of motor function after VM transplantation. Moreover, OECs possibly promote the elongation of dopaminergic and serotonergic axon in the bridging graft. Copyright © 2015 John Wiley & Sons, Ltd.

The Effect of Sertoli Cells on Xenotransplantation and Allotransplantation of Ventral Mesencephalic Tissue in a Rat Model of Parkinson’s Disease

“…A hemiparkinsonian rat model was generated as previously described [39]. Briefly, eight-week-old male SD rats were deeply anesthetized with Zolitel (20 mg/kg, i.p.…”

“…VM tissues used to establish allotransplantation and xenotransplantation models were obtained from embryonic day 14 SD rats and embryonic day 27 Lee-Sung pigs [39,43,44]. Dissection areas were selected according to a previous study, with some modifications [40,45].…”

Emerging regenerative medicine and tissue engineering strategies for Parkinson’s disease

“…Alternative strategies have been explored to improve targeted striatal reinnervation from fetal mesencephalic tissue grafted in the substantia nigra, such as injecting kainate between the midbrain and striatum to create a trophic environment for axonal outgrowth. 110 Although kainate administration was shown to increase striatal dopamine release and reduced motor behavioral deficits, kainate is an excitatory neurotoxin, thus significantly limiting its potential regenerative strategy for patients with PD. 111 Following this approach, a similar strategy has been investigated using GDNF as an attractant for guiding transplanted axons from the SNpc to the striatum.…”

Olfactory ensheathing cells improve the survival of porcine neural xenografts in a Parkinsonian rat model

“…The PD model rats (n = 24) were generated as previously reported. 30 Briefly, a male SD rat fully anesthetized with Zoletil 50 (20 mg/kg intraperitoneal injection; Virbac) was unilaterally injected with 6-hydroxydopamine (6-OHDA, 20 μg in 4 μL saline containing 0.02% ascorbic acid;…”

“…29 These data may explain why in a co-graft situation OECs can enhance the survival of rat fetal ventral mesencephalon tissue in the striatum of the PD rats. 30,31 But, there is still no report determining whether OECs improve the survival of xenografted pfVM cells.…”