In neurodegenerative disease and in acute brain injury, there is often local up-regulation of neurotrophin production close to the site of the lesion. Treatment by direct injection of neurotrophins and growth factors close to these lesion sites has repeatedly been demonstrated to improve recovery. It has therefore been proposed that transplanting viable neurotrophin-producing cells close to the trauma lesion, or site of degenerative disease, might provide a novel means for continuous delivery of these molecules directly to the site of injury or to a degenerative region. The aim of this paper is to summarize recent published information and present new experimental data that indicate that long-lasting therapeutic implants of choroid plexus (CP) neuroepithelium may be used to treat brain disease. CP produces and secretes numerous biologically active neurotrophic factors (NT). New gene microarray and proteomics data presented here indicate that many other anti-oxidant, anti-toxin and neuronal support proteins are also produced and secreted by CP cells. In the healthy brain, these circulate in the cerebrospinal fluid through the brain and spinal cord, maintaining neuronal networks and associated cells. Recent publications describe how transplanted CP cells and tissue, either free or in an immunoprotected encapsulated form, can effectively deliver therapeutic molecules when placed near the lesion or site of degenerative disease in animal models. Using simple techniques, CP neuroepithelial cell clusters in suspension culture were very durable, remaining viable for 6 months or more in vitro. The cell culture conditions had little effect on the wide range and activity of genes expressed and proteins secreted. Recently, completed experiments show that implanting CP within alginate-poly-ornithine capsules effectively protected these xenogeneic cells from the host immune system and allowed their survival for 6 months or more in the brains of rats, causing no adverse effects. Previously reported evidence demonstrated that CP cells support the survival and differentiation of neuronal cells in vitro and effectively treat acute brain injury and disease in rodents and non-human primates in vivo. The accumulated preclinical data together with the long-term survival of implanted encapsulated cells in vivo provide a sound base for the investigation of these treatments for chronic inherited and established neurodegenerative conditions.
Parkinson's disease (PD) is a neurodegenerative disease that is primarily characterized by degeneration of dopaminergic (DA) neurons in the substantia nigra (SN) and a loss of their fibre projections in the striatum. We utilized the neonatal porcine choroid plexus (CP), an organ that secretes cerebrospinal fluid containing various types of neurotrophic and neuroprotective factors, to ameliorate the Parkinsonian symptoms in MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated rhesus monkeys without requiring immunosuppression. We demonstrate that transplanted encapsulated CP clusters (eCPs) significantly improved neurological functions in MPTP-treated monkeys during the course of six months after transplantation (p < 0.001) when compared with monkeys implanted with empty capsules or subjected to sham surgery. The improvement in neurological scores was accompanied by a corresponding improvement in apomorphine-induced circling behaviour (p < 0.001) as well as increased tyrosine hydroxylase (TH) staining in the striatum. Our results suggest that eCPs are a promising cell therapeutic agent to treat Parkinson's disease.
Capsules containing porcine choroid plexus cells release therapeutic molecules that stimulate regeneration of the lesioned nigrostriatum in rats.
The curative effect of minimally invasive surgery on palmar and foot hyperhidrosis and its influence on serum-related cytokines and immunoglobulins were investigated. Seventy-six patients with palmar and foot hyperhidrosis admitted to Yunnan University Hospital from August 2014 to July 2016 were selected and randomly divided into control group (n=38) and observation group (n=38) using a random number table. Patients in control group received drug therapy, while those in observation group underwent laparoscopic thoracic-4 sympathetic chain combined with thoracic-3 branch amputation. The therapeutic effects of patients in the two groups were compared. The levels of serum C-reactive protein (CRP), interleukin-6 (IL-6), IL-10 and tumor necrosis factor-α (TNF-α) of patients in the two groups were measured by enzyme-linked immunosorbent assay (ELISA) before treatment and at one week after treatment. The levels of immunoglobulin G (IgG), IgA and IgM were detected by immunoturbidimetry. The quality of life (QOL) in patients was evaluated by quality-of-life index (iQOL) before and after treatment. The total effective rate in the observation group was significantly higher than that in the control group (P<0.05). The serum levels of CRP, IL-6, IL-10 and TNF-α of patients in the two groups were higher at one week after treatment than those before treatment (P<0.05), and there were no significant differences between the two groups (P>0.05). At one week after treatment, IgG, IgM and IgA levels of patients in the two groups were remarkably increased (P<0.05), and there were no significant differences between the two groups (P>0.05). After treatment, the iQQL scores of patients in the two groups were significantly decreased, and iQQL score in observation group was decreased more significantly compared with that in control group (P<0.05). Compared with drug therapy, minimally invasive surgery is more effective in the treatment of palmar and foot hyperhidrosis with smaller trauma and inflammatory reaction, and it has less influence on serum immunoglobulin levels, which is conducive to the rehabilitation of patients.
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