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Biomedical subjects

S R Winn

Publications and source records attributed to S R Winn.

At least 37 records · Page 2Linked to original sources
PubMed1995

Implantation of encapsulated catecholamine and GDNF-producing cells in rats with unilateral dopamine depletions and parkinsonian symptoms.

Studies in rodents suggest that PC12 cells, encapsulated in semipermeable ultrafiltration membranes and implanted in the striatum, have some potential efficacy for the treatment of age- and 6-OHD-induced sensorimotor impairments (22, 70, 71, 74). The objectives of this study were to: (1) determine if baby hamster kidney cells engineered to secrete glial cell line-derived neurotrophic factor (BHK-GDNF) would survive encapsulation and implantation in a dopamine-depleted rodent striatum, (2) compare polymer-encapsulated PC12 and PC12A cells in terms of their ability to survive and produce catecholamines in vivo in a dopamine-depleted striatum, and (3) determine if BHK-GDNF, PC12, or PC12A cells reduce parkinsonian symptoms in a rodent model of Parkinson's disease. Capsules with BHK-GDNF or PC12 cells contained viable cells after 90 days in vivo, with little evidence of host tissue damage/gliosis. In rats with tyrosine hydroxylase (TH)-positive fibers remaining in the lesioned striatum, there was TH-positive fiber ingrowth into the membranes of the BHK-GDNF capsules. PC12-containing capsules had higher basal release of both dopamine and L-DOPA after 90 days in vivo than before implantation, while basal release of both dopamine and L-DOPA decreased in the PC12A-containing capsules. Both encapsulated PC12 and PC12A cells, but not encapsulated BHK-GDNF cells, decreased apomorphine-induced rotations. Parkinsonian symptoms (akinesia, freezing/bracing, sensorimotor neglect) related to the extent of dopamine depletion were evident even in rats with dopamine depletions of only 25%. Evidence that encapsulated cells may attenuate these parkinsonian symptoms was not detected but most of the rats were more severely depleted of dopamine than Parkinson's patients (less than 2% dopamine remaining in the entire striatum), and these tests were not sensitive to differences between rats with less than 10% dopamine remaining. These results suggest that cell encapsulation technology can safely provide site-specific delivery of dopaminergic agonists or growth factors within the CNS, without requiring suppression of the immune system, and without using fetal tissue. Of the three types of encapsulated cells examined in the present study, PC12 cells seem to offer the most therapeutic potential in rats with severe dopamine depletions.

Animals↗
PubMed1994

The aged monkey basal forebrain: rescue and sprouting of axotomized basal forebrain neurons after grafts of encapsulated cells secreting human nerve growth factor.

Six Rhesus monkeys between 24 and 29 years of age received unilateral transections of the fornix. Three monkeys then received intraventricular transplants of polymer-encapsulated baby hamster kidney (BHK) fibroblasts that had been genetically modified to secrete human nerve growth factor (hNGF). The remaining three monkeys received identical grafts except the cells were not modified to secrete hNGF. Monkeys receiving the fornix transection and control grafts displayed extensive reductions in the number of choline acetyltransferase- (57-75%) and p75 NGF receptor- (53%) immunoreactive medial septal neurons ipsilateral to the lesion/implant. In contrast, monkeys receiving transplants of encapsulated hNGF-secreting cells display only a modest loss of choline acetyltransferase- (0-36%) and p75 NGF receptor-(7-22.4%) immunoreactive septal neurons. Additionally, all monkeys receiving the hNGF-secreting implants, but none receiving control implants, displayed robust sprouting of cholinergic fibers within the septum ipsilateral to the transplant. Just prior to sacrifice, the capsules were retrieved and found to contain viable BHK cells releasing biologically relevant levels of hNGF. These data demonstrate that hNGF can provide trophic and tropic influences to aged primate basal forebrain neurons undergoing lesion-induced degeneration, supporting the contention that hNGF may prevent the degeneration of basal forebrain neurons in Alzheimer disease.

Aging↗
PubMed1994

Implants of polymer-encapsulated human NGF-secreting cells in the nonhuman primate: rescue and sprouting of degenerating cholinergic basal forebrain neurons.

Baby hamster kidney (BHK) cells were genetically modified to secrete high levels of human nerve growth factor (BHK-hNGF). Following polymer encapsulation, these cells were implanted into the lateral ventricle of four cynomolgus monkeys immediately following a unilateral transection/aspiration of the fornix. Three control monkeys received identical implants, with the exception that the BHK cells were not genetically modified to secrete hNGF and thus differed only by the hNGF construct. One monkey received a fornix transection only. All monkeys displayed complete transections of the fornix as revealed by a comprehensive loss of acetylcholinesterase-containing fibers within the hippocampus ipsilateral to the lesion. Control monkeys that were either unimplanted or received BHK-control (non-NGF secreting) cell implants did not differ from each other and displayed extensive losses of choline acetyltransferase and p75 NGF receptor (NGFr)-immunoreactive neurons within the medial septum (MS; 53 and 54%, respectively) and vertical limb of the diagonal band (VLDB; 21 and 30%, respectively) ipsilateral to the lesion. In contrast, monkeys receiving implants of BHK-hNGF cells exhibited a only a modest loss of cholinergic neurons within the septum (19 and 20%, respectively) and VLDB (7%). Furthermore, only implants of hNGF-secreting cells induced a dense sprouting of cholinergic fibers within the septum, which ramified against the ependymal lining of the ventricle adjacent to the transplant site. Examination of the capsules retreived from monkeys just prior to their death revealed an abundance of cells that produced detectable levels of hNGF in a sufficient concentration to differentiate PC12A cells in culture. These findings support the use of polymer-encapsulated cell therapy as a potential treatment for neurodegenerative diseases such as Alzheimer disease where basal forebrain degeneration is a consistent pathological feature. Moreover, this encapsulated xenogeneic system may provide therapeutically effective levels of a number of neurotrophic factors, alone or in combination, to select populations of neurons within the central nervous system.

Acetylcholine↗
PubMed1994

Polymer-encapsulated cells genetically modified to secrete human nerve growth factor promote the survival of axotomized septal cholinergic neurons.

Effective treatments for neurodegenerative disorders are limited by our inability to alter the progression of the diseases. A number of proteins have specific neuroprotective activities in vitro; however, the delivery of these factors into the central nervous system over the long term at therapeutic levels has been difficult to achieve. BHK cells engineered to express and release human nerve growth factor were encapsulated in an immunoisolation polymeric device and transplanted into both fimbria-fornix-lesioned rat brains and naive controls. In the lesioned rat brain, chronic delivery of human nerve growth factor by the encapsulated BHK cells provided nearly complete protection of axotomized medial septal cholinergic neurons. Human nerve growth factor continued to be released by encapsulated cells upon removal from the aspirative site after 3 weeks or from normal rat striatum after 3 and 6 months in vivo. Long-term encapsulated cell survival was confirmed by histologic analysis. This encapsulated xenogeneic system may provide therapeutically effective amounts of a number of neurotrophic factors, alone or in combination, to virtually any site within the body.

Analysis of Variance↗
PubMed1994

Implantation of polymer-encapsulated human nerve growth factor-secreting fibroblasts attenuates the behavioral and neuropathological consequences of quinolinic acid injections into rodent striatum.

Delivery of neurotrophic molecules to the central nervous system has gained considerable attention as a potential strategy for the treatment of neurological disorders. In the present study, a DHFR-based expression vector containing the human nerve growth factor gene (hNGF) was transfected into a baby hamster fibroblast cell line (BHK). Using an immunoisolatory polymeric device, encapsulated BHK-control cells and those secreting hNGF (BHK-hNGF) were transplanted unilaterally into rat lateral ventricles. Three days later, the same animals received unilateral injections of quinolinic acid (QA, 225 nmol) or the saline vehicle into the ipsilateral striatum. Approximately 2 weeks following surgery, animals were tested for apomorphine-induced rotation behavior. Animals which received BHK-hNGF cells rotated significantly less than those animals receiving BHK-control cells or QA alone. Histological analysis 29-30 days following capsule implantation demonstrated that BHK-hNGF cells attenuated the extent of host neural damage produced by QA as assessed by a sparing of ChAT- and NADPH-d-positive neurons. Moreover, a lessened GFAP reaction was apparent within the striatum of animals receiving BHK-hNGF cells. As measured by ELISA, hNGF was released by the encapsulated BHK-hNGF cells prior to implantation and following removal. Morphology of retrieved capsules revealed numerous viable and mitotically active BHK cells. These results suggest that implantation of polymer-encapsulated hNGF-releasing cells can be used to protect neurons from excitotoxin damage.

Animals↗
PubMed1994

Intrastriatal implants of polymer-encapsulated PC12 cells: effects on motor function in aged rats.

1. The feasibility of ameliorating the motor deficits in aged rats was evaluated in animals receiving polymer-encapsulated PC12 cells. 2. Motor coordination and balance was evaluated in young (5-6 month) and aged (24-25 month) rats. Compared to the young animals, the aged animals fell more rapidly from a rotating rod and were unable to maintain their balance on a series of wooden beams of varying widths. 3. Following baseline testing, aged animals received either no implant, empty capsules or PC12 cell-loaded capsules implanted bilaterally into the striatum. 4. Three weeks following surgery, animals were re-tested and a significant improvement in balance on the rotorod and wooden beams was observed in those aged animals receiving PC12 cell-loaded capsules. No improvements or decrements in performance were observed in those animals receiving empty. Histological analysis revealed the presence of surviving tyrosine hydroxylase-positive PC12 cells randomly distributed within the capsules.

Animals↗
PubMed1993

Polymer-encapsulated PC12 cells promote recovery of motor function in aged rats.

The feasibility of using polymer-encapsulated PC12 cells to ameliorate the motor deficits in aged rats was evaluated. Spontaneous locomotion and motor coordination was evaluated in young (5-6 month) and aged (24-25 month) rats. Aged animals tested for spontaneous locomotor activity in Digiscan animal activity monitors were found to be hypoactive relative to young animals. Compared to the young animals the aged animals: (1) remained suspended from a horizontal wire for less time, (2) were unable to descend a wooden pole covered with wire mesh in a coordinated manner, (3) fell more rapidly from a rotating rod, and (4) were unable to maintain their balance on a series of wooden beams with either a square or rounded top of varying widths. Prior to implantation PC12 cell-loaded capsules were chromatographically characterized for catecholamine release. Following baseline testing, aged animals received either no implant, empty capsules, or PC12 cell-loaded capsules implanted bilaterally into the striatum. Three weeks following surgery, animals were retested and a significant improvement in balance on the rotorod and wooden beams was observed in those aged animals receiving PC12 cell-loaded capsules. No recovery was observed in the animals receiving PC12 cell-loaded capsules on any of the other motor tasks. Likewise, no improvement was observed on any behavioral measure in those animals receiving empty capsules. Histological analysis revealed the presence of numerous surviving tyrosine hydroxylase-positive PC12 cells within the capsules. Encapsulated PC12 cells survive following implantation into aged rats and such a technique may be useful for treating some of the behavioral consequences of aging.

Aging↗
PubMed1993

Locomotion of aged rats: relationship to neurochemical but not morphological changes in nigrostriatal dopaminergic neurons.

Spontaneous locomotion and motor coordination was evaluated in young (5-6 month old) and aged (24-25 month old) rats. Animals were tested for spontaneous locomotor activity in Digiscan Animal Activity Monitors during the nocturnal cycle. Aged animals exhibited a significant hypoactivity compared to their young counterparts. Evaluation of the time course of activity revealed that the young animals had a cyclical pattern of activity during the 12-hour testing period with clear peaks at 2-4 hours after the initiation of testing and at 8- to 10-hour intervals thereafter. In contrast, the aged animals exhibited a blunted initial activity peak. During the remainder of the test period the aged animals activity was stable with no further peaks in activity. Compared to the young animals the aged animals also (a) remained suspended from a horizontal wire for less time, (b) were unable to descend a wooden pole covered with wire mesh in a coordinated manner, (c) fell more rapidly from a rotating rod and (d) were unable to maintain their balance on a series of wooden beams with either a square or rounded top of varying widths. Histological analysis demonstrated that there was no reduction in the number, area, or length of tyrosine hydroxylase-immunoreactive neurons within the A8, A9, or A10 region of the aged animals. Neurochemical analysis revealed that while DA and HVA levels were not decreased in the aged rats, DOPAC levels, as well as the ratios of DA/DOPAC and DA/HVA, were decreased. These results indicate that neurochemical but not morphological changes within the nigrostriatal dopaminergic system underlie the deficits in motor behavior observed in aged rats.

Aging↗
PubMed1992

Growth of tumour cell lines in polymer capsules: ultrastructure of encapsulated PC12 cells.

Recent studies indicate that polymer-encapsulated PC12 cells release sufficient amounts of dopamine to significantly alter behavioural paradigms in animals with unilateral lesions of dopaminergic midbrain neurons. Because cell fine structure provides a useful measure for assessment of storage function, exocytosis, metabolism, cell activity and cell viability, we examined the ultrastructure of PC12 cells grown in semi-permeable polymer capsules maintained in vitro or implanted into the forebrain of rats or guinea pigs. Encapsulated PC12 cells remained viable and continued to divide for the entire evaluation period of six months. Overall morphologies of encapsulated PC12 cells were similar in both environments and they resembled PC12 cells grown in monolayer cultures. In short-term cultures, encapsulated PC12 cells typically contained abundant quantities of chromaffin cell-like granules. The encapsulated cells had initially abundant microvilli on their surfaces which decline in frequency over time. After long-term enclosure for ten weeks or more, fewer secretory granules were detected in the cytoplasm of cells in capsules cultured in vitro and in brain-implanted capsules. Some cells in implanted capsules had long slender filipodia that were not present on PC12 cells in cultured capsules. The morphological changes of PC12 cells may correlate with altered growth conditions such as serum and oxygen concentrations, the presence or absence of growth factors in different environments, and with changes of cell interactions related to cell densities and build up of debris within the capsules over time. Since dopaminergic PC12 pheochromocytoma cells remain viable in semi-permeable polymer capsules for at least six months, such 'cell-capsules' could provide an alternative to dopamine-secreting embryonic neural grafts in dopamine replacement therapies.

Animals↗
PubMed1992

A novel approach to neural transplantation in Parkinson's disease: use of polymer-encapsulated cell therapy.

Transplantation of dopaminergic neurons derived from fetal or adrenal tissue into the striatum is a potentially useful treatment for Parkinson's disease (PD). Although initially promising, recent clinical studies using adrenal autografts have demonstrated limited efficacy. The use of human fetal cells, despite promising preliminary results, is complicated by tissue availability and ethical concerns. An attractive alternative is based on encapsulating dopamine-producing cells into polymer capsules prior to transplantation. Polymer capsules can be fabricated to surround the cells with a semi-permeable and immunoprotective barrier. The semi-permeable membrane allows nutrients to enter the capsule, so the encapsulated cells will survive and function, and dopamine and other low molecular weight constituents to diffuse out into the host tissue. Thus, the technique allows use of unmatched human tissue (allografts), or even animal tissue (xenografts) without immunosuppression of the recipient. Cell-loaded polymer capsules can also be retrieved if necessary or desired. The demonstration that striatal implants of encapsulated dopamine-producing cells promote behavioral recovery in rodent and primate models of PD further suggests that cellular encapsulation may be a useful strategy for ameliorating the behavioral consequences of PD.

Adrenal Medulla↗
PubMed1992

Polymer-encapsulated PC12 cells: long-term survival and associated reduction in lesion-induced rotational behavior.

Intrastriatal implantation of a dopaminergic cell line surrounded by a permeable, thermoplastic membrane was investigated as a method of long-term dopamine (DA) delivery within the central nervous system (CNS). An increase in DA release from PC12 cell-loaded capsules maintained in vitro was associated with an increase in mitotic activity of the encapsulated cell line. A significant reduction in apomorphine-induced rotational behavior was observed after PC12 cell-containing capsules were implanted into unilaterally 6-hydroxydopamine (6-OHDA) lesioned rats, which was sustained for 24 wk. Four wk after implantation, microdialysis studies revealed the presence of DA near PC12 cell-containing capsules, which was comparable to extracellular striatal levels of unlesioned controls. Extracellular striatal DA was undetectable by microdialysis in lesioned animals near empty polymer capsules. Histological analysis after 24 wk in vivo demonstrated that encapsulated PC12 cells survived, continued to express tyrosine hydroxylase, and that encapsulation prevented tumorigenesis. The data suggested that the release of a diffusible substance, most likely DA, from an implant is sufficient to exert a long-term functional influence upon 6-OHDA unilaterally lesioned rats and that capsules containing DA-secreting cells may be an effective method of long-term DA delivery in the CNS.

Acrylic Resins↗
PubMed1991

Transplantation of microencapsulated bovine chromaffin cells reduces lesion-induced rotational asymmetry in rats.

Surrounding bovine chromaffin cells by a semipermeable membrane may protect the transplanted cells from a host immune response and shield them from the inflammatory process resulting from the surgical trauma. Encapsulation of the chromaffin cells was achieved by interfacial adsorption of a polycation on a polyanionic colloid matrix in which the chromaffin cells were entrapped. Basal and potassium-evoked release of catecholamines from encapsulated bovine chromaffin cells was analyzed over a 4-week period in vitro. Norepinephrine and dopamine release remained constant over time whereas epinephrine release significantly decreased. The chromaffin cells also retained the capacity for depolarization-elicited catecholamine release 4 weeks following the encapsulation procedure. Morphological analysis revealed the presence of intact chromaffin cells with well-preserved secretory granules. Striatal implantation of chromaffin cell-loaded capsules significantly reduced apomorphine-induced rotation compared to empty polymer capsules in animals lesioned with 6-hydroxydopamine for at least 4 weeks. Intact chromaffin cells expressing tyrosine hydroxylase and dopamine-beta-hydroxylase were observed in all capsules implanted in the striatum for 4 weeks. The assessment of the clinical potential of transplanting encapsulated adrenal chromaffin cells of either allo- or xenogeneic origin for Parkinson's disease will require long-term behavioral studies. The present study suggests, however, that the polymer encapsulation procedure may offer an alternative to adrenal autografts as a source of dopaminergic tissue.

Animals↗
PubMed1991

Repair of the blood-brain barrier following implantation of polymer capsules.

Past studies of polymer-encapsulated cell lines implanted in the brain indicated their usefulness for transmitter replacement therapy in animal models. Such grafts may have potentially important clinical applications, but their placement into neural parenchyma may cause a traumatic injury resulting in a leaky blood-brain barrier around the implant. This study investigated whether or not injury repair and reformation of the barrier takes place near a polymer capsule implanted in the brain of Sprague-Dawley rats. The two methods used for detection of a leaky barrier were immunocytochemical localization of extravasated serum albumin and circulating Evans blue that binds to serum albumin. Immunocytochemical staining for glial filament protein provided a measure for evaluating injury associated gliosis. Polymer capsules implanted for 10, 16 and 18 days were surrounded by microvessels that leaked detectable quantities of serum albumin into interstitial spaces and, by secondary uptake, into some nearby neurons and reactive astrocytes. Reactive astroglia were observed within the outer regions of the capsule wall and in the near vicinity of the implant after these early survival times. In contrast, at post-implantation times of 46 and 54 days, serum albumin was no longer detected in the neural parenchyma near the macrocapsules and only few reactive astrocytes remained. These findings show that polymer capsules implanted within the cerebrum permit (a) reformation of the blood-brain barrier and (b) occurrence of repair processes that lead to minimal deposition of reactive astroglia near the implanted polymer capsule.

Animals↗
PubMed1991

Behavioral recovery following intrastriatal implantation of microencapsulated PC12 cells.

The motor deficits associated with Parkinson's disease may be ameliorated by intrastriatal placement of dopamine-secreting cells in a polymer capsule. Water soluble polyelectrolytes were utilized for membrane encapsulation of dopamine-secreting PC12 cells. Membrane permeability studies revealed exclusion of radiolabeled 69,000 Da albumin, whereas 30,000 Da carbonic anhydrase was able to cross the membrane. No cytolytic activity was observed following incubation of the encapsulated PC12 cells with PC12 cell-directed antiserum and fresh complement. In vitro, dopamine release and the surface area of intact cells per microcapsule, reached a plateau at 4 weeks that was maintained for at least 12 weeks. Viable PC12 cells were observed in microcapsules implanted for 4 and 8 weeks in nonlesioned guinea pig striata. The behavioral effect of intrastriatal dopamine release from microencapsulated PC12 cells was evaluated in the 6-hydroxydopamine unilaterally lesioned rat model. From 1 to 4 weeks postimplantation a significant reduction in rotation behavior under apomorphine challenge was observed with PC12 cell-loaded microcapsules as compared to empty microcapsules. Tyrosine hydroxylase immunopositive PC12 cells were observed 4 weeks postimplantation in all animals exhibiting a reduction in turning behavior. Implantation of polymer-encapsulated cells may provide a means for long-term delivery of neurotransmitters and growth factors to the nervous system.

Animals↗
PubMed1991

Long-term cross-species brain transplantation of a polymer-encapsulated dopamine-secreting cell line.

Cross-species transplantation of dopamine-releasing cell lines protected against immune rejection by a semi-permeable synthetic membrane may provide a source of neurotransmitters for the treatment of Parkinson's disease. Experiments were carried out to assess whether polymer-encapsulated PC12 cells, a catecholaminergic cell line derived from a rat pheochromocytoma, could survive in vitro as well as in vivo after implantation in the striatum of adult guinea pigs. When maintained in vitro, the encapsulated PC12 cells exhibited good survival, proliferated, and spontaneously released dopamine for at least 6 months. They also retained the capacity for depolarization-elicited dopamine release. In vivo, well-preserved tyrosine hydroxylase-positive PC12 cells were observed in capsules implanted for 4, 8, and 12 weeks. Unencapsulated PC12 cells or cells in nonintact capsules did not survive transplantation at any of these time periods. The survival of encapsulated PC12 cells transplanted across species suggests that polymer encapsulation may provide an alternative for xenotransplantation of secretory cells in the absence of systemic immunosuppression.

Adrenal Gland Neoplasms↗
PubMed1991

Macroencapsulation of dopamine-secreting cells by coextrusion with an organic polymer solution.

A new method of coextruding living cells in the core of a forming hollow fibre is described. PC12 cells, an immortalized cell line which secretes large amounts of dopamine, and dissociated bovine adrenal chromaffin cells, a non-dividing cell type which also secretes dopamine, were coextruded by a dry-jet wet spinning technique through a double-lumen spinneret from a 15% weight by volume solution of poly(acrylonitrile vinyl chloride) in either dimethylsulphoxide (DMSO), dimethylacetamide (DMAC) or dimethylformamide (DMF). Closure of the fibre was achieved by mounting polytetrafluoroethylene tubes on a rotating coaxial wheel system which squeezed the forming hollow fibre at regular intervals. Spontaneous and potassium-stimulated release of catecholamines from the macrocapsules were quantified under static conditions by ion-pair reverse-phase high-performance liquid chromatography equipped with electrochemical detection at 2, 4 and 6 wk. At all time periods, coextruded macrocapsules with either PC12 cells or adrenal chromaffin cells released dopamine under either unstimulated or stimulated conditions. An increase over time in dopamine release was observed from PC12 cell coextruded macrocapsules with observable difference between capsules extruded with DMSO, DMAC or DMF as solvents. Well-preserved PC12 cells and adrenal chromaffin cells were present in coextruded macrocapsules with no observable difference between capsules extruded with DMSO, DMAC or DMF as inocuity of macroencapsulation by coextrusion from an organic polymer solution. Owing to the particular fluid dynamics of this technique, minimal potentially toxic cell-solvent contact occurs allowing the use of a wider range of water-insoluble polymeric systems.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1991

Transplantation of polymer encapsulated neurotransmitter secreting cells: effect of the encapsulation technique.

Deficits associated with neurological diseases may be improved by the transplantation within the brain lesioned target structure of polymer encapsulated cells releasing the missing neurotransmitter. Surrounding cells with a permselective membrane of appropriate molecular weight cut-off allows inward diffusion of nutrients and outward diffusion of neurotransmitters, but prevents immunoglobulins or immune cells from reaching the transplant. This technique therefore allows transplantation of post-mitotic cells across species. It also permits neural grafting of transformed cell lines since the polymer capsule prevents the formation of tumors by physically sequestering the transplanted tissue. In the present study, we compared the ability of dopamine-secreting cells, encapsulated by 2 different methods, to reverse experimental Parkinson's disease, a neurodegenerative disease characterized by motor disturbances due to a lack of dopamine within the striatum following degeneration of the dopaminergic nigro-striatal pathway. PC12 cells were loaded in polyelectrolyte-based microcapsules or thermoplastic-based macrocapsules and maintained in vitro or transplanted in a rat experimental Parkinson model for 4 weeks. Chemically-induced depolarization increased the in vitro release of dopamine from macrocapsules over time, while no increase in release was observed from microcapsules. Encapsulated PC12 cells were able to reduce lesion-induced rotational asymmetry in rats for at least 4 weeks, regardless of the encapsulation technique used. With both encapsulation methods, PC12 cell viability was greater in vivo than in vitro which suggests that the striatum releases trophic factors for PC12 cells. More brain tissue damage was observed with microcapsules than macrocapsules, possibly the result of the difficulty of manipulating the more fragile microcapsules.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗