Intravitreal Implantation of Genetically Modified Autologous Bone Marrow-Derived Stem Cells for Treating Retinal Disorders
| Autor: | Mark D. Kirk, Cheryl A. Jensen, Leilani J. Castaner, Jeffrey N. Bryan, Christopher J. Tracy, Douglas N. Sanders, Martin L. Katz |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Retinal degeneration medicine.medical_specialty Pathology Retinal Disorder genetic structures Genetic Vectors Green Fluorescent Proteins Bone Marrow Cells Mice Transgenic Biology Mesenchymal Stem Cell Transplantation Transplantation Autologous Article 03 medical and health sciences chemistry.chemical_compound Dogs Lysosomal storage disease medicine Animals Cells Cultured Retina Retinal Degeneration Mesenchymal stem cell Gene Transfer Techniques Mesenchymal Stem Cells Retinal Genetic Therapy Dependovirus medicine.disease eye diseases Surgery Mice Inbred C57BL Vitreous Body 030104 developmental biology medicine.anatomical_structure Microscopy Fluorescence chemistry Intravitreal Injections Neuronal ceroid lipofuscinosis sense organs Stem cell Peptide Hydrolases |
| Zdroj: | Retinal Degenerative Diseases ISBN: 9783319171203 |
| DOI: | 10.1007/978-3-319-17121-0_76 |
| Popis: | A number of retinal degenerative diseases may be amenable to treatment with continuous intraocular delivery of therapeutic agents that cannot be delivered effectively to the retina via systemic or topical administration. Among these disorders are lysosomal storage diseases resulting from deficiencies in soluble lysosomal enzymes. Most cells, including those of the retina, are able to take up these enzymes and incorporate them in active form into their lysosomes. In theory, therefore, continuous intraocular administration of a normal form of a soluble lysosomal enzyme should be able to cure the molecular defect in the retinas of subjects lacking this enzyme. Experiments were conducted to determine whether genetically modified bone marrow-derived stem cells implanted into the vitreous could be used as -vehicles for continuous delivery of such enzymes to the retina. Bone marrow-derived mesenchymal stem cells (MSCs) from normal mice were implanted into the vitreous of mice undergoing retinal degeneration as a result of a mutation in the PPT1 gene. The implanted cells appeared to survive indefinitely in the vitreous without proliferating or invading the retina. This indicates that intravitreal implantation of MSCs is likely a safe means of long-term delivery of proteins synthesized by the implanted cells. Experiments have been initiated to test the efficacy of using genetically modified autologous MSCs to inhibit retinal degeneration in a canine model of neuronal ceroid lipofuscinosis. |
| Databáze: | OpenAIRE |
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