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Publications and source records attributed to I Date.

At least 55 records · Page 3Linked to original sources
PubMed1996

Chromaffin cell survival from both young and old donors is enhanced by co-grafts of polymer-encapsulated human NGF-secreting cells.

Following polymer-encapsulation, human nerve growth factor-secreting baby hamster kidney fibroblasts (BHK-hNGF) were implanted into the striatum of hemiparkinsonian rats together with unencapsulated adrenal medullary chromaffin cells from either young (2 weeks) or old (12 months) donor rats. Animals receiving both BHK-hNGF cells and chromaffin cells exhibited significant decreases (39-56%) in apomorphine-induced rotational behaviour which was equivalent regardless of the age of the donor tissue. Histological analysis revealed that while survival of chromaffin cells without hNGF support was poor, co-grafts of adrenal medulla and BHK/hNGF cells increased chromaffin cell survival by 20 times. Again, this effect was independent of the age of the donor tissue. Retrieved capsules contained numerous viable encapsulated BHK-hNGF cells which continued to release hNGF. These results further indicate the potential use of intrastriatal implantation of encapsulated hNGF-secreting cells for augmenting the survival of co-grafted chromaffin cells as well as promoting the functional recovery of hemiparkinsonian rats.

Age Factors↗
PubMed1996

Neural transplantation and trophic factors in Parkinson's disease: special reference to chromaffin cell grafting, NGF support from pretransected peripheral nerve, and encapsulated dopamine-secreting cell grafting.

Since adrenal medullary chromaffin cells produce catecholamines as wel l as several kinds of neurotrophic factors which affect dopamine neurons, the authors have investigated the methods to increase the survival of grafted chromaffin cells in parkinsonian model animals. Measurement of nerve growth factor (NGF) showed that NGF level at the distal stump of the pretransected peripheral nerve increased significantly, thus, we have applied cografting of chromaffin cells with this stump of the peripheral nerve to animal models of Parkinson's disease since chromaffin cell survival have been reported to be increased by supplementation of nerve growth factor (NGF) in vitro and in vivo. By this cografting approach, not only the chromaffin cell survival but also the host intrinsic dopaminergic system recovery were enhanced. This effect continued 2 years in our long-term study The effects of donor and host ages were investigated and the results showed that the effects were more prominent when young donors or hosts were used compared with aging donors or hosts. Although cografting of adrenal medulla with peripheral nerve was applied successfully in parkinsonian patients with favorable results, it may be difficult to apply this procedure in aged patients since this is autografting and adrenal medulla itself may be affected by the disease in aged patients. Polymer-encapsulated dopamine-secreting cells are another donor candidates and can be applied combined with stereotaxic thalamotomy or pallidotomy for the patients with Parkinson's disease in the near future.

Age Factors↗
PubMed1996

Histological analysis of microencapsulated dopamine-secreting cells in agarose/poly(styrene sulfonic acid) mixed gel xenotransplanted into the brain.

PC12 cells were encapsulated within agarose/poly-(styrene sulfonic acid) (agarose/PSSa) mixed gel and xenotransplanted into the brains of guinea pigs. The immunoprotection capability and biocompatibility of the agarose/PSSa microcapsules were evaluated. Tyrosine hydroxylase-positive PC12 cells within the microcapsules were observed in all guinea pigs at least 5 weeks after transplantation. PC12 cells had a relatively uniform small size and occasionally formed cell clusters; however, cell necrosis was not apparent. The host reaction to agarose/PSSa microcapsules was minimal. The degree of glial fibrillary acidic protein-positive astrocyte density around the microcapsules was similar to that around the injection tracks. Necrosis around the brain/microcapsule interface was not apparent as assessed by Nissl staining. Normal-appearing neurons were observed in close vicinity to the capsule. High-performance liquid chromatography with electrochemical detection showed basal and potassium-evoked release of dopamine from the PC12 cell-enclosed microcapsules in vitro. We conclude that encapsulation using agarose/PSSa mixed gel can not only isolate the enclosed cells from the host immune system but can also allow diffusional exchange of nutrients and neurotransmitters. Encapsulation using agarose/PSSa mixed gel may expand the range of donor tissues for neural transplantation.

Animals↗
PubMed1996

Parkinson's disease, trophic factors, and adrenal medullary chromaffin cell grafting: basic and clinical studies.

Neural transplantation is one of the promising approaches for the treatment of Parkinson's disease. Although the strategy of using adrenal medulla as donor tissue, rather than fetal nigra tissue, started as an alternative method, recent experimental studies demonstrated the efficacy of adrenal medulla grafting as a neurotrophic source. Many methods to increase the survival of grafted chromaffin cells have been developed, some of which have already been applied clinically with encouraging results. This review summarizes the advancements of adrenal medulla grafting in basic and clinical studies. Special attention is focused on the relationship with neurotrophic factors and how we can enhance the survival of grafted chromaffin cells.

Adrenal Medulla↗
PubMed1996

Chromaffin cell survival and host dopaminergic fiber recovery in a patient with Parkinson's disease treated by cografts of adrenal medulla and pretransected peripheral nerve. Case report.

A 55-year-old woman with severe Parkinson's disease was treated by cografting adrenal medulla with pretransected peripheral nerve into the bilateral caudate nuclei. The patient showed modest improvement of her akinesia; this effect persisted for 1 year after transplantation, when she suddenly died from upper gastrointestinal bleeding unrelated to the grafting procedure. At autopsy, a large number of tyrosine hydroxylase-immunoreactive chromaffin cells were observed within the caudate graft sites and a dense network of host dopaminergic fibers was visualized. This autopsy finding is very important for the field of experimental and clinical chromaffin cell grafting because it is the first evidence that cografts using pretransected peripheral nerve might enhance the survival of chromaffin cells and the recovery of host dopaminergic fibers in humans suffering from Parkinson's disease.

Adrenal Medulla↗
PubMed1996

Cografting with polymer-encapsulated human nerve growth factor-secreting cells and chromaffin cell survival and behavioral recovery in hemiparkinsonian rats.

Encapsulated cell grafting is one approach for the delivery of neurotransmitters and/or neurotrophic factors to the brain. Baby hamster kidney (BHK) cells were genetically modified to secrete high levels of human nerve growth factor (hNGF). Following polymer encapsulation, these cells were implanted into the left lateral ventricle or the left striatum 1.5 mm away from striatally cografted unencapsulated adrenal medullary chromaffin cells in hemiparkinsonian rats. Although the animals receiving adrenal medulla alone or adrenal medulla with intraventricular hNGF-secreting cell grafting did not show recovery of apomorphine-induced rotational behavior, the animals receiving adrenal medulla with intrastriatal hNGF-secreting cell implants showed a significant recovery of rotational behavior 2 and 4 weeks after transplantation. Histological analysis revealed that in animals receiving adrenal medulla with intraventricular hNGF-secreting cell grafting, the number of tyrosine hydroxylase-immunoreactive (TH-IR) surviving chromaffin cells tended to be higher (approximately five to six times) than in animals receiving adrenal medulla alone; however, this increase did not reach statistical significance. In contrast, in animals receiving adrenal medullary cells together with intrastriatal hNGF-secreting cells, the number of TH-IR surviving chromaffin cells was more than 20 times higher than that in animals receiving adrenal medullary cells alone. Analysis of retrieved capsules revealed that hNGF continued to be released by encapsulated BHK-hNGF cells after 4 weeks in vivo. Moreover, histological analysis confirmed the presence of numerous viable encapsulated BHK-hNGF cells. These results indicate the potential use of intrastriatal implantation of encapsulated hNGF-secreting cells for augmenting the survival of cografted chromaffin cells as well as promoting the functional recovery of hemiparkinsonian rats. These data indicate that this approach may have potential application for treating Parkinson's disease.

Animals↗
PubMed1996

[Encapsulated dopamine-secreting cells transplanted into the brain: a possible therapy for Parkinson's disease].

Encapsulation of neurosecretory cells within a semipermeable membrane may possibly isolate the enclosed cells from the host immune system and allow inward diffusion of nutrients and outward diffusion of neurotransmitters. Moreover, the encapsulation procedure may prevent the tumor formation of enclosed cells, when they are derived from tumor cells. In the present study, PC12 cells, a dopaminergic cell line derived from a rat pheochromocytoma, were enclosed within an agarose/poly (styrene sulfonic acid) (agarose/PSSa) mixture and transplanted into the brains of rats (allogeneic transplantation) or guinea pigs (xenogeneic transplantation). Tyrosine hydroxylase (TH) immunoreactive PC12 cells within the microcapsules were observed in all rats and guinea pigs at least up to five weeks after transplantation. PC12 cells were round in shape and of relatively uniform small size. Although PC12 cells occasionally formed cell clusters, the formation of a tumor was not observed. The host reaction to agarose/PSSa microcapsules was minimum. The degree of glial fibrillary acidic protein (GFAP) positive astrocyte density around the microcapsules was similar to that around injection tracks. There was no apparent immunological rejection around the capsules. High-performance liquid chromatography with electrochemical detection (HPLC-EC) showed basal and potassium-evoked release of dopamine from the PC12 cell-enclosed microcapsules in vitro. Although our data is preliminary, we believe that agarose/PSSa microcapsules are promising for producing semipermeable membranes that enable allo-and xenotransplantation of neurosecretory cells into the brain in the absence of systemic immunosuppression. This approach is expected to be applied in Parkinson's disease in the near future.

Adrenal Gland Neoplasms↗
PubMed1995

Neovascularization of rat fetal neocortical grafts transplanted into a previously prepared cavity in the cerebral cortex: a three-dimensional morphological study using the scanning electron microscope.

Neovascularization within syngeneic rat fetal neocortical grafts transplanted into a previously prepared cavity in the cerebral cortex was studied 1 to 3 months after transplantation, utilizing scanning electron microscopy of vascular corrosion casts. The grafts were easily identified and the outer surface of the grafts, especially at the host-graft interface, was surrounded by large regenerated vessels of leptomeninges and connective tissue (e.g. dura). Large vessels originating from the choroid plexus also coated the grafts in animals whose lateral ventricles had been opened at the time of cavitation. These large regenerated vessels were mainly observed on the surface of the grafts, and they ramified markedly to form capillary networks in the vicinity of the host-graft interface. Occasionally several relatively large regenerated vessels were noted to extend into the grafts, and to ramify and connect with graft capillary networks having the same features as that of the host brain. Moreover, direct vascular connections between host capillaries and those within the grafts were observed. In some animals, arteries and arterioles which fed the grafts were identified in the perimeter of the grafts with their characteristic morphology. The interior microvasculature structure of the grafts was largely composed of the capillary network of graft origin, and of several relatively large penetrating vessels originating from the regenerated leptomeningeal vessels or the vessels of the choroid plexus. The present study demonstrated that the blood supply to the solid grafts transplanted into the previously prepared cavities originated primarily from the regenerated host vessels. These host vessels perfused the intrinsic graft vessels via new anastomoses which formed predominantly at the host-graft interface.

Animals↗
PubMed1995

Three-dimensional morphological study of microvascular regeneration in cavity wall of the rat cerebral cortex using the scanning electron microscope: implications for delayed neural grafting into brain cavities.

The present study was carried out to quantify the subsequent vascular regeneration around a lesion cavity made in the rat cerebral cortex and to decide the origin of the regenerated microvessels. A quantitative study utilizing computerized image analysis after microvascular perfusion with India ink indicated approximately 25 and 160% increase of the vascular density adjacent to the cavity compared to the contralateral cortex at 4 and 21 days, respectively, after lesioning. The microvasculature around the cavity was also evaluated by scanning electron microscopy of vascular corrosion casts. Newly formed leptomeningeal vessels began to grow down toward the floor of the cavity 4 days after lesioning and nearly covered the walls of the cavity 21 days after lesioning. A neovascular network of leptomeninges and connective tissue (e.g., dura) was formed as a roof over the cavity. Numerous branches of these newly formed vessels and prominent anastomoses with the capillary network in the walls and floor of the cavity were observed. Newly formed vessels also originated from the choroid plexus in cases where the lateral ventricle had been opened at the time of lesioning. These results document the plasticity of the vascular system in the cerebral cortex after a mechanical injury. The regenerated vascular network may offer a suitable condition for survival of transplanted tissues.

Animals↗
PubMed1995

Two-year follow-up study of a patient with Parkinson's disease and severe motor fluctuations treated by co-grafts of adrenal medulla and peripheral nerve into bilateral caudate nuclei: case report.

We performed co-grafts of adrenal medulla and peripheral nerve into the bilateral caudate nuclei of a 43-year-old patient with advanced Parkinson's disease who showed severe daily motor fluctuations before surgery. There were no postoperative complications, and a 2-year follow-up result is presented. The patient showed a gradual and significant amelioration of the parkinsonian symptoms starting 2 weeks after transplantation. The alleviation of akinesia during "off" periods was the most apparent clinical improvement and continued for 2 years after surgery. The dosage of L-dopa/benserazide was significantly reduced after surgery compared with that before surgery. The results indicate that co-grafts of adrenal medulla with peripheral nerve may be useful for the treatment of Parkinson's disease in the long term.

Activities of Daily Living↗
PubMed1994

Effect of host age upon the degree of nigrostriatal dopaminergic system recovery following cografts of adrenal medulla and pretransected peripheral nerve.

Accumulation of nerve growth factor (NGF) has been reported to occur at the distal stump of pretransected peripheral nerve. We performed adrenal medullary grafts or cografts of adrenal medulla and distal stump of pretransected peripheral nerve into the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated young or aging mice. We subsequently compared the survivability of chromaffin cells and the degree of host dopaminergic (DA) fiber recovery in relation to host age. In both young and aging hosts, adrenal medullary chromaffin cells cografted with pretransected peripheral nerve survived better than those in adrenal grafts alone. Host DA fiber recovery, however, showed less recovery and more restriction around the grafted site in aging compared with young hosts. We conclude that pretransected peripheral nerve can enhance the survivability of cografted chromaffin cells both in young and in aging hosts, but that DA fiber recovery is more limited in aging hosts compared to young hosts.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1994

Increased nerve growth factor level in the distal stump of transected sciatic nerve in relation to aging and its application for neural grafting.

The nerve growth factor (NGF) level in the distal stump of mouse sciatic nerve transected 24 h before increased significantly compared with that in the nontransected contralateral side. This level was higher in aged (24-month-old) mice than in aging (12-month-old) or in young (1-month-old) mice. Adrenal medullary tissue mixed with the pretransected (24 h before) distal stump of the sciatic nerve of aged mice was cografted into the ipsilateral striatum of aged mice with a unilateral 6-hydroxydopamine lesion of dopaminergic system. Two and 4 weeks after transplantation, cografted mice showed partial functional compensation in amphetamine-induced motor asymmetry while mice with adrenal grafts alone did not show the functional recovery. The immunocytochemical staining of tyrosine hydroxylase revealed large numbers of chromaffin cells surviving in cografted animals. It is concluded that NGF level in the distal stump of pretransected peripheral nerve is increased even in aged animals and cografting of this nerve stump with adrenal medulla can be effectively utilized in aged animals with nigrostriatal insufficiency.

Adrenal Medulla↗
PubMed1994

Efficacy of pretransection of peripheral nerve for promoting the survival of cografted chromaffin cells and recovery of host dopaminergic fibers in animal models of Parkinson's disease.

Nerve growth factor (NGF) concentration in the distal stump of the transected peripheral nerve has been shown to increase more than 20 times one day after transection. We performed adrenal medullary alone grafts or cografts of adrenal medulla and acutely transected or pretransected (24 h before) sciatic nerve into the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, and compared the survival of chromaffin cells and the recovery of the host-intrinsic dopaminergic fibers using tyrosine hydroxylase immunocytochemistry and high-performance liquid chromatography. We also performed peripheral nerve alone grafting (acutely transected or pretransected) for comparison. Adrenal medullary chromaffin cells cografted with pretransected sciatic nerve survived better than those in adrenal grafts alone or those cografted with acutely transected sciatic nerve. Host dopaminergic fiber recovery was also most prominent in mice cografted with pretransected peripheral nerve. Animals receiving grafts of peripheral nerve alone showed limited recovery of host dopaminergic fibers and the degree of recovery was lower than that of animals receiving cografts of adrenal medulla with pretransected peripheral nerve. We conclude that pretransected peripheral nerve enhanced the survival of cografted chromaffin cells and this increased survival led to promote the recovery of host-intrinsic dopaminergic fibers. This grafting procedure might be promising in application to patients with Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1993

Xenogeneic dopaminergic grafts reverse behavioral deficits induced by 6-OHDA in rodents: effect of 15-deoxyspergualin treatment.

Foetal rat mesencephalic dopamine-containing tissue was transplanted into the lateral ventricle of mice previously subjected to a 6-OHDA lesion of dopaminergic nerve terminals in the corpus striatum. The graft recipients were immunosuppressed by subcutaneous injections of 15-deoxyspergualin (DSG). Four weeks postgrafting, all DSG-treated mice showed partial or complete functional compensation in amphetamine-induced motor asymmetry. The immunohistochemical staining of tyrosine hydroxylase (TH) revealed large numbers of surviving dopamine neurons and abundant fibers in the grafted animals. In contrast, all grafts in non-DSG-treated animals were rejected and functional compensation was lacking. It is concluded that DSG treatment promotes xenogeneic intracerebral graft survival, recovery of function and reduce the histological sign of rejection.

Amphetamine↗