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Dwaine F Emerich

Publications and source records attributed to Dwaine F Emerich.

At least 19 recordsLinked to original sources
PubMed2006

Extensive neuroprotection by choroid plexus transplants in excitotoxin lesioned monkeys.

Huntington's disease (HD) results from degeneration of striatal neurons. Choroid plexus (CP) cells secrete neurotrophic factors, and CP transplants are neuroprotective in rat models of HD. To determine if similar neuroprotective effects could be obtained in primates, porcine CP was encapsulated in alginate capsules. PCR confirmed that the CP cells expressed transthyretin and immunocytochemistry demonstrated typical ZO-1 and tubulin staining. In vitro, CP conditioned media enhanced the survival and preserved neurite number and length on serum deprived neurons. Cynomolgus primates were transplanted with CP-loaded capsules into the caudate and putamen followed by quinolinic acid (QA) lesions 1 week later. Control monkeys received empty capsules plus QA. Choroid plexus transplants significantly protected striatal neurons as revealed by stereological counts of NeuN-positive neurons (8% loss vs. 43% in controls) and striatum volume (10% decrease vs. 40% in controls). These data indicate that CP transplants might be useful for preventing the degeneration of neurons in HD.

Animals↗
PubMed2006

The pinpoint promise of nanoparticle-based drug delivery and molecular diagnosis.

Nanotechnology, or systems/device manufacture at the molecular level, is a multidisciplinary scientific field undergoing explosive development. The genesis of nanotechnology can be traced to the promise of revolutionary advances across medicine, communications, genomics and robotics. Without doubt one of the greatest values of nanotechnology will be in the development of new and effective medical treatments (i.e., nanomedicine). This review focuses on the potential of nanomedicine as it specifically relates to (1) the development of nanoparticles for enabling and improving the targeted delivery of therapeutic agents; (2) developing novel and more effective diagnostic and screening techniques to extend the limits of molecular diagnostics providing point-of-care diagnosis and more personalized medicine.

Animals↗
PubMed2006

Intraperitoneal stability of alginate-polyornithine microcapsules in rats: an FTIR and SEM analysis.

Alginate-polycation microcapsule systems have been used over decades as delivery vehicles for cell and protein therapy. These systems have been unpredictable across a range of indications with questions resulting around the inherent stability of the alginate polysaccharide and failure mode of the delivery system. The current study focuses on such a system using 5 different alginates, 2 of which are commercially purified, which are crosslinked by polyornithine. Capsules formed by frequency-generated droplet formation were studied in the peritoneal cavity of Long-Evans rats over the course of 3 months by morphometry, Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy of the surface. Individual capsule components were also investigated on FTIR and a relative stability index was generated by titration for comparison to explanted samples over time. Using these techniques, a distinct degradation pattern was noted and is compared between the 5 alginate sources.

Alginates↗
PubMed2006

Choroid plexus transplants in the treatment of brain diseases.

The choroid plexus (CP) produces and secretes numerous biologically active neurotrophic factors into the cerebrospinal fluid (CSF). These circulate throughout the brain and spinal cord, maintaining neuronal networks and associated cells. In neurodegenerative disease and in acute brain injury there is 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 choroid plexus cells close to the lesion might provide a novel means for continuous delivery of these molecules directly to the site of injury. Recent publications describe how transplanted CP, either free or in an immunoprotected encapsulated form, deliver therapeutic molecules to the desired site. This review briefly describes the accumulated evidence that CP cells support neuronal cells in vitro and have therapeutic properties when transplanted to treat acute and chronic brain disease and injury in animal models.

Animals↗
PubMed2006

Intracompartmental delivery of CNTF as therapy for Huntington's disease and retinitis pigmentosa.

Ciliary neurotrophic factor (CNTF) is a cytokine with neurotrophic activity across a broad spectrum of peripheral and central nervous system (CNS) cells. While its therapeutic potential for CNS diseases has been clear for sometime, the blood brain barrier (BBB) hinders the systemic delivery of CNTF and direct bolus injections are not suitable due to the short half-life of CNTF. One means of overcoming the BBB while providing continuous delivery of CNTF is with immunoisolated cellular implants that produce and deliver CNTF directly to the region of interest. Cells can be protected from host rejection by encapsulating, or surrounding, them within an immunoisolatory, semipermeable membrane that admits oxygen and required nutrients and releases bioactive cell secretions, but restricts passage of larger cytotoxic agents from the host immune defense system. The selective membrane eliminates the need for chronic immunosuppression of the host and allows the implanted cells to be obtained from nonhuman sources. In this review we discuss cell immunoisolation for Huntington's disease and retinitis pigmentosa. These two indications are highlighted because of extensive pre-clinical data supporting the general concept and recent clinical data that both strengthens the theoretical role of CNTF for treating neurodegeneration and justifies additional clinical evaluation in these and other diseases.

Animals↗
PubMed2005

Managing chronic pain with encapsulated cell implants releasing catecholamines and endogenous opiods.

Spinal injections (intrathecal) of norepinephrine and/or opiod agonists are antinociceptive and when administered together may act in synergy. Spinal implants of adrenal chromaffin cells are an effective method for sustained delivery of the analgesic substances norepinephrine and enkephalin to the central nervous system (CNS). One method of packaging and implanting cell-loaded devices into the intrathecal space of recipients is by encapsulating the cell suspensions in a polymer membrane prior to implantation. Cells/tissue packaged within an encapsulating membrane obviate the need for immunosuppressive therapies in transplant recipients. In addition, device output can be quantified prior to implantation, and following the removal of the spinal implant. The ability to retrieve the devices with the present tubular configuration also confers an additional margin of safety over unencapsulated chromaffin cell implants. This paper reviews the research and clinical observations of cellular transplants containing adrenal chromaffin cells for relieving chronic pain. Encapsulated cell technology is discussed with an emphasis on our experiences developing pain-modulating clinical devices. The human-sized prototype devices were loaded with enzymatically isolated bovine chromaffin cells and maintained in vitro for 7 - 8 days in serum-free media. Two days prior to implantation, each device was assayed by static incubation to measure catecholamine and met-enkephalin output, and qualified devices (n = 6) were implanted into the sheep subarachnoid space for 6 weeks. Following a 6 week in life period, the retrieval forces of prototype devices were measured during removal from the subarachnoid space. Static incubation of the devices immediately following retrieval and after a 24 hour re-incubation period were used to quantify norepinephrine and met-enkephalin secretion profiles. This study demonstrated the safety, retrievability and maintenance of pharmacologically active encapsulated chromaffin cell-loaded devices with human implant dimensions.

Animals↗
PubMed2005

The choroid plexus in the rise, fall and repair of the brain.

The choroid plexuses (CPs) are involved in the most-basic aspects of neural function including maintaining the extracellular milieu of the brain by actively modulating chemical exchange between the CSF and brain parenchyma, surveying the chemical and immunological status of the brain, detoxifying the brain, secreting a nutritive "cocktail" of polypeptides and participating in repair processes following trauma. This diversity of functions may mean that even modest changes in the CP can have far-reaching effects. Indeed, changes in the anatomy and physiology of the CP have been linked to aging and several CNS diseases. It is also possible that replacing diseased or transplanting healthy CP might be useful for treating acute and chronic brain diseases. This review focuses on the wide-ranging and under-appreciated functions of the CP, alterations of these functions in aging and neurodegeneration, and recent demonstrations of the therapeutic potential of transplanted CP for neural trauma.

Aging↗
PubMed2005

Nanomedicine--prospective therapeutic and diagnostic applications.

Nanotechnology, or systems/device manufacture at the molecular level, is a multidisciplinary scientific field undergoing explosive development. The genesis of nanotechnology can be traced to the promise of revolutionary advances across medicine, communications, genomics and robotics. Without doubt, one of the greatest values of nanotechnology will be in the development of new and effective medical treatments (i.e., nanomedicine). This review focuses on the potential of nanomedicine, including the development of nanoparticles for diagnostic and screening purposes, DNA sequencing using nanopores, manufacture of drug delivery systems and single-virus detection.

Drug Delivery Systems↗
PubMed2005

A role of the choroid plexus in transplantation therapy.

The choroid plexuses (CPs) play pivotal roles in the most basic aspects of neural function. Some of the roles of the CP include maintaining the extracellular milieu of the brain by actively modulating chemical exchange between the CSF and brain parenchyma, surveying the chemical and immunological status of the brain, detoxifying the brain, secreting a nutritive "cocktail" of polypeptides, and participating in repair processes following trauma. This diversity of functions suggests that even modest changes in the CP can have far reaching effects. Indeed, changes in the anatomy and physiology of the CP have been linked to several CNS diseases. It is also possible that replacing diseased CP or transplanting healthy CP might be useful for treating acute and chronic brain diseases. Here we describe the wide-ranging functions of the CP, alterations of these functions in aging and neurodegeneration, and recent demonstrations of the therapeutic potential of transplanted CP for neural trauma.

Aging↗
PubMed2004

Neuroprotection by encapsulated choroid plexus in a rodent model of Huntington's disease.

Choroid plexus from neonatal pigs was encapsulated in alginate microcapsules and transplanted into the rat striatum. Three days later, the same animals received unilateral injections of quinolinic acid (225 nmol) into the ipsilateral striatum. Choroid plexus transplants ameliorated the weight loss and motor impairments resulting from QA. Histological analysis demonstrated that choroid plexus transplants reduced the volume of striatal damage and protected ChAT-, but not NADPH-diaphorase-positive neurons. These data are the first to demonstrate that transplanted choroid plexus cells can protect striatal neurons from excitotoxic damage and that this strategy may ultimately prove relevant for the treatment of Huntington's disease.

Alginates↗
PubMed2004

Intracerebral transplantation of porcine choroid plexus provides structural and functional neuroprotection in a rodent model of stroke.

BACKGROUND AND PURPOSE: Choroid plexus (CP) secretes a cocktail of neurotrophic factors. In the present study, CP from neonatal pigs was encapsulated within alginate microcapsules for in vitro and in vivo neuroprotective studies. METHODS: In vitro studies involved serum deprivation of rat embryonic cortical neurons and treatment with a range of concentrations of conditioned media from CP. For in vivo studies, rats received a 1-hour middle cerebral artery occlusion followed by intracranial transplantation of encapsulated or unencapsulated CP, empty capsules, or no transplant. Behavioral testing was conducted on days 1 to 3 after transplantation. Cerebral infarction was analyzed using 2,3,5-triphenyl-tetrazolium chloride staining at 3 days after transplantation. RESULTS: Conditioned media from CP produced a significant dose-dependent protection of serum-deprived cortical neurons. Enzyme-linked immunosorbent assay confirmed secretion of GDNF, BDNF, and NGF from CP. Parallel in vivo studies showed that CP transplants improved behavioral performance and decreased the volume of infarction. Both encapsulated and unencapsulated CP transplants were effective; however, more robust benefits accompanied encapsulated transplants. CONCLUSIONS: These data are the first to demonstrate the neuroprotective potential of transplanted CP and raise the intriguing possibility of using these cells as part of the treatment regimen for stroke and other neurological disorders.

Alginates↗
PubMed2004

Sertoli cell grafts for Huntington's disease. An opinion.

The role of inflammation in CNS diseases is controversial, but growing evidence suggests that anti-inflammatory agents can minimize and/or prevent neural degeneration and its associated behavioral consequences. Sertoli cells can be grafted into the CNS to locally deliver molecules with known trophic and anti-inflammatory effects on the surrounding tissue. When Sertoli cells are grafted into the 3-nitropropionic acid (3-NP) model of Huntington's disease the protective effects are quite similar to those obtained using systemic treatments with NSAIDS (Salzberg-Benhouse et al., J. Pharmacol. Exp. Ther. 306:218-228, 2003). While these data alone do not provide unequivocal support for the notion that Sertoli cell grafts exert their beneficial effects via modulating local inflammation, they do provide an interesting convergence between data sets. The benefits of Sertoli cell grafts should be more thoroughly examined in animal models of inflammation.

Humans↗
PubMed2004

Use of Sertoli cell transplants to provide local immunoprotection for tissue grafts.

The recent success of allogeneic islet transplantation for the treatment of type I diabetes has renewed interest in cell therapy for diseases of secretory cell dysfunction. Unfortunately, widespread clinical use of cell transplantation is limited by tissue availability and the need for long-term immunosuppresion. Testicular Sertoli cells can confer local immunoprotection for co-transplanted cells and may provide a means of overcoming the obstacles associated with cell transplantation. Sertoli cell grafts protect islets in animal models of diabetes and can be transplanted into the brain to enhance regeneration and promote the survival of co-grafted tissues. This review describes the role that Sertoli cells normally play in testicular immunology, details the preclinical data using transplanted Sertoli cells in models of diabetes and Parkinson's disease and discusses some of the possible mechanisms involved in this phenomena, as well as the future of this technology.

Animals↗
PubMed2004

The choroid plexus: function, pathology and therapeutic potential of its transplantation.

The choroid plexus (CP) produces cerebrospinal fluid (CSF) and forms the blood-CSF barrier. However, the CP may have additional functions in the CNS beyond these traditional roles. Preclinical and clinical studies in ageing and neurodegeneration demonstrate anatomical and physiological changes in CP, suggesting roles in normal and pathological conditions and potentially endogenous repair processes following trauma. One of the broadest functions of the CP is establishing and maintaining the extracellular milieu throughout the brain and spinal cord, in part by secreting numerous growth factors into the CSF. The endogenous secretion of growth factors raises the possibility that transplantable CP might enable delivery of these molecules to the brain, while avoiding the conventional molecular and genetic alterations associated with modifying cells to secrete selected products. This review describes some of the anatomical and functional changes of CP in ageing and neurodegeneration, and recent demonstrations of the therapeutic potential of transplanted CP for neural trauma.

Adult↗
PubMed2004

Eleventh Annual Conference of the American Society for Neural Transplantation and Repair.

The Eleventh Annual Conference of the American Society for Neural Transplantation and Repair was held at the Sheraton Sand Key Resort in Clearwater Florida over a typically warm and sunny 4 days. The scientific programme was organised by Dr T Collier of Rush Presbyterian Medical Center and Dr P Bickford of the University of South Florida. The 2004 conference was attended by a large portion of the approximately 300 society members. The purpose of the meeting was to bring together clinicians and basic researchers focused on areas ranging from understanding the biology of degenerative CNS diseases to utilising a variety of cell-based therapies to prevent neuronal cell death or repair and reconstitute damaged brain circuits.

Animals↗
PubMed2004

Use of human umbilical cord blood (HUCB) cells to repair the damaged brain.

Neurodegenerative diseases as well as acute center nervous system (CNS) injuries remains a problematic and frustrating area of medicine in terms of treatments and cures, which is mostly due to the complex circuitry of the CNS along with our limited knowledge. Therapeutically, the last two and a half decades have offered new hope for those suffering from neurodegenerative diseases or injuries with advent of new drug discoveries and cellular therapies. Cell transplantation is a compelling and potential treatment for certain neurological and neurodegenerative diseases as well as for acute injuries to the spinal cord and brain. The hematopoietic system offers an alternative source of cells that is easily obtainable, abundant, and reliable when compared to cells obtained from fetal or embryonic origins. Human umbilical cord blood (HUCB) cells have been used clinically for over ten years to treat both malignant and non-malignant diseases. With in the last five years these cells have been used pre-clinically in animal models of brain and spinal cord injuries, in which functional recovery have been shown. This paper reviews the advantages, utilization, and progress of HUCB cells in the field of cellular transplantation and repair.

Blood Cells↗
PubMed2004

Transgenic Sertoli cells as a vehicle for gene therapy.

Gene therapy involves the manipulation of genetic material to replace defective or deficient proteins to restore function in disease states. These genes are introduced into cells by mechanical, chemical, and biological approaches. To date, cell-based gene therapy has been hampered by the lack of an abundant, safe, and immunologically acceptable source of tissue. As an alternative, transgenic animals designed to produce therapeutic proteins could overcome some of the issues facing gene therapy but the problem of immune rejection of the tissue remains. This article reports on recently published work indicating the potential to use transgenic Sertoli cells surviving in an allogeneic host by virtue of their ability to create a locally immunoprivileged environment, thereby providing for the continued delivery of a therapeutic protein to the systemic circulation.

Animals↗