164 results about "Retinal pigment epithelial cell" patented technology

The production of high quality retinal pigmented epithelium (RPE) cells is necessary for research and potential therapeutic uses. Especially desirable are methods for the production of RPE cells using xeno-free culture conditions. Disclosed herein are novel methods for the production of RPE cells from pluripotent cells with high yields, including xeno-free production methods. Also provided are methods of efficiently isolating RPE cells from cultures containing heterogeneous cell types, allowing for substantially pure RPE cell cultures to be established. Additionally, novel methods for the cryopreservation of RPE cells are provided.

The present invention relates to a composition for implantation in the subretinal space of an eye, the composition including amniotic membrane, which may be cryopreserved human amniotic membrane, and a plurality of retinal pigment epithelial (RPE) cells or RPE equivalent cells present at the amniotic membrane. The amniotic membrane may be intact, epithelially denuded, or otherwise treated. The invention includes the use of amniotic membrane for the culturing of RPE cells thereon, forming a surgical graft for replacement of Bruch's membrane as a substrate, and for the transplanting of RPE cells to the subretinal space. The composition does not elicit immunological reactions to alloantigens or to RPE specific autoantigens; and exerts anti-inflammatory, anti angiogentic, and anti-scarring effects. The invention includes methods and kits for making or using composites including amniotic membrane and RPE cells. Also disclosed is a device for harvesting RPE cells.

The invention relates to a method of producing a retinal pigment epithelial cell from a human pluripotent stem cell, and a method of treating or preventing a retinal disease by using the produced cell. The retinal pigment epithelial cell is prepared by (a) inducing differentiation of a human pluripotent stem cell into a pigment cell by adhesion cultivation of a human pluripotent stem cell in a medium containing a Nodal signal inhibitor and a Wnt signal inhibitor in the absence of a feeder cell to give a culture containing the pigment cell, (b) subjecting the obtained culture to further adhesion culture to give a culture containing a pigment cell colony, and (c) isolating the pigment cell from the obtained culture and culturing the cell to give a retinal pigment epithelial cell.

The present invention concerns RPE cells obtainable by directed differentiation from stem cell, particularly, human stem cells. It has been specifically found that culturing stem cells in the presence of one or more member of the TGFβ superfamily, such as Activin A) induced directed differentiation into mature and functional RPE cells. This was evidenced by the expression of markers specific to mature RPE cells, including MiTF-A, RPE65 or Bestrophin). In accordance with one particular embodiment, the cells are a priori cultured with nicotinamide (NA) which was found to augment the cells' response to the inductive effect of the one or more member of the TGFβ superfamily. The invention also provides methods of performing the directed differentiation, as well as methods for use of the resulting RPE cells.

A unique DHA product, 10, 17S-docosatriene (“Neuroprotectin D1” or “NPD1”), was found to provide surprisingly effective neuroprotection when administered right after an experimental stroke. Moreover, both nerve cells and retinal pigment epithelial (RPE) cells were found to synthesize 10,17S-docosatriene (NPD1) from DHA. NPD1 also potently counteracted H2O2 / TNFα oxidative stress-mediated cell apoptotic damage. Under the same oxidative-stress conditions, NPD1 up-regulated the anti-apoptotic Bcl-2 proteins, Bcl-2 and Bcl-xL, and decreased expression of the pro-apoptotic proteins, Bad and Bax. Moreover, in RPE cells NPD1 inhibited oxidative stress-induced caspase-3 activation, IL-1β-stimulated human COX-2 promoter expression, and apoptosis due to N-retinylidene-N-retinylethanolamine (A2E). Overall, NPD1 protected both nerve and retinal pigment epithelial cells from cellular apoptosis and damage due to oxidative stress. NPD1 concentration in the brain of Alzheimer's patients was found to be significantly decreased from that of controls. In cultured human brain cells, NPD1 synthesis was up-regulated by neuroprotective soluble β amyloid, and NPD1 was found to inhibit secretion of toxic β amyloid peptides.

The present invention provides devices and methods for applying radiation to the retina of a patient. In one embodiment, an apparatus includes a radiation source for generating a radiation beam suitable for absorption by retinal pigment epithelial cells. One or more optical components are included to direct the beam onto the retina. A scanner is optically coupled to the radiation source to control movement of the beam in two dimensions to allow a scan over the retina. A controller applies control signals to the scanner to adjust beam movement to illuminate a plurality of retinal locations in a temporal sequence according to a predefined pattern. The device can be operated in one mode to effect selective targeting of retinal pigment epithelial cells, or in another mode to effect thermal photocoagulation of the retina.

The present invention relates to a composition for implantation in the subretinal space of an eye, the composition including amniotic membrane, which may be cryopreserved human amniotic membrane, and a plurality of retinal pigment epithelial (RPE) cells or RPE equivalent cells present at the amniotic membrane. The amniotic membrane may be intact, epithelially denuded, or otherwise treated. The invention includes the use of amniotic membrane for the culturing of RPE cells thereon, forming a surgical graft for replacement of Bruch's membrane as a substrate, and for the transplanting of RPE cells to the subretinal space. The composition does not elicit immunological reactions to alloantigens or to RPE specific autoantigens; and exerts anti-inflammatory, and angiogentic, and anti-scarring effects. The invention includes methods and kits for making or using composites including amniotic membrane and RPE cells. Also disclosed is a device for harvesting RPE cells.

The present invention provides improved methods for producing RPE cells from human embryonic stem cells or from other human pluripotent stem cells. The invention also relates to human retinal pigmented epithelial cells derived from human embryonic stem cells or other human multipotent or pluripotent stem cells. hRPE cells derived from embryonic stem cells are molecularly distinct from adult and fetal-derived RPE cells, and are also distinct from embryonic stem cells. The hRPE cells described herein are useful for treating retinal degenerative diseases.

The invention relates to the field of cell culture, specifically, the derivation of retinal pigmented epithelial cells from pluripotent cells. The invention comprises the use of various cell culture medium supplements, medium formulations, and methods of using such medium supplements and formulations, in order to effect the rapid differentiation of pluripotent cells into retinal pigmented epithelial cells with very high yields. The invention further includes cell culture media formulations for the efficient maintenance, propagation, and maturation of cultured retinal pigmented epithelial cells.

Disclosed are capsid-modified rAAV particles and expression vectors, as well as compositions and pharmaceutical formulations that comprise them. Also disclosed are methods of preparing and using novel capsid-protein-mutated particle or rAAV vector constructs in a variety of diagnostic and therapeutic applications including, inter alia, as delivery agents for diagnosis, treatment, or amelioration of one or more diseases, disorders, or dysfunctions of the mammalian eye. Also disclosed are methods for subretinal delivery of therapeutic gene constructs to mammalian photoreceptors and retinal pigment epithelial cells, as well as use of the disclosed compositions in the manufacture of medicaments for a variety of in vitro and / or in vivo applications including the treatment of a variety of inherited retinal diseases.

The present invention provides improved methods for producing RPE cells from human embryonic stem cells or from other human pluripotent stem cells. The invention also relates to human retinal pigmented epithelial cells derived from human embryonic stem cells or other human multipotent or pluripotent stem cells. hRPE cells derived from embryonic stem cells are molecularly distinct from adult and fetal-derived RPE cells, and are also distinct from embryonic stem cells. The hRPE cells described herein are useful for treating retinal degenerative diseases.

A retinal implant is provided that uses an artificial biocompatible material as a support material on which retinal pigment epithelial cells, iris pigment epithelial cells, and / or stem cells can be deposited either in situ or in vivo. The support material has a surface topology that is rough to promote cell adhesion, has surface pits to allow pigment cells to grow into, and has pores to allow for proper diffusion of materials. The support material serves as a substrate for cell growth and as a patch for damaged basement membrane (Bruch's membrane). This cell-coated membrane or pigment cell-enriched membrane is surgically positioned in the sub-retinal space to rescue or restore photoreceptor cell function that may be damaged or threatened by degenerative diseases of the eye, such as age-related macular degeneration.

The present invention concerns RPE cells obtainable by directed differentiation from stem cell, particularly, human stem cells. It has been specifically found that culturing stem cells in the presence of one or more member of the TGFβ superfamily, such as Activin A) induced directed differentiation into mature and functional RPE cells. This was evidenced by the expression of markers specific to mature RPE cells, including MiTF-A, RPE65 or Bestrophin). In accordance with one particular embodiment, the cells are a priori cultured with nicotinamide (NA) which was found to augment the cells' response to the inductive effect of the one or more member of the TGFβ superfamily. The invention also provides methods of performing the directed differentiation, as well as methods for use of the resulting RPE cells.

Provided are methods and compositions for maintaining the viability of photoreceptor cells and / or retinal pigment epithelial cells in a subject with an ocular disorder including, for example, age-related macular degeneration (AMD) (e.g., dry or neovascular AMD), retinitis pigmentosa (RP), or a retinal detachment. The viability of the photoreceptor cells and / or the retinal pigment epithelial cells can be preserved by administering a necrosis inhibitor either alone or in combination with an apoptosis inhibitor to a subject having an eye with the ocular condition. The compositions, when administered, maintain the viability of the cells, thereby minimizing the loss of vision or visual function associated with the ocular disorder.

The present invention provides devices and methods for applying radiation to the retina of a patient. In one embodiment, an apparatus includes a radiation source for generating a radiation beam suitable for absorption by retinal pigment epithelial cells. One or more optical components are included to direct the beam onto the retina. A scanner is optically coupled to the radiation source to control movement of the beam in two dimensions to allow a scan over the retina. A controller applies control signals to the scanner to adjust beam movement to illuminate a plurality of retinal locations in a temporal sequence according to a predefined pattern. The device can be operated in one mode to effect selective targeting of retinal pigment epithelial cells, or in another mode to effect thermal photocoagulation of the retina.

The invention relates to the field of cell culture, specifically, the derivation of retinal pigmented epithelial cells from pluripotent cells. The invention comprises the use of various cell culture medium supplements, medium formulations, and methods of using such medium supplements and formulations, in order to effect the rapid differentiation of pluripotent cells into retinal pigmented epithelial cells with very high yields. The invention further includes cell culture media formulations for the efficient maintenance, propagation, and maturation of cultured retinal pigmented epithelial cells.

The invention provides a preparation method of a functionalized retinal pigment epithelial cell graft. The preparation method comprises the following steps: taking a nano bionic Bruch's membrane as a retinal pigment epithelial cell carrier, inoculating retinal pigment epithelial cells onto the nano bionic Bruch's membrane, and performing co-culture under low-serum and low-sugar culture conditions to obtain the functionalized retinal pigment epithelial cell graft, wherein the nano bionic Bruch's membrane is an ultrathin porous antheraea pernyi silk fibroin / polycaprolactone / gelatin compound nanofiber membrane prepared by dissolving the antheraea pernyi silk fibroin, polycaprolactone and the gelatin in an organic solvent to form an electrostatic spinning solution and performing electrostatic spinning on the electrostatic spinning solution by an electrostatic spinning method. The functionalized retinal pigment epithelial (RPE) cell graft prepared by the method is capable of effectively avoiding the problems of high possibility of the RPE cells, cell polarity disorder and the like after transplantation in a conventional method, and can be widely applied to cell transplantation.

The present invention relates to methods for characterizing a test agent using a fluorescently detectable αvβ3 and αvβ5 integrin specific agent and a retinal pigment epithelial cell. The invention further relates to kits having a fluorescently detectable αvβ3 and αvβ5 integrin specific agent and a retinal pigment epithelial cell.

The invention relates to a nerve stem cell injection made from retina pigment epithelial cell, to treat paralysis agitans, wherein said injection at least comprises 3*106 nerve stem cells of human hRPE, while said nerve stem cells are cultivated from retina pigment epithelial cells. And its production comprises that: (1), separating and cultivating cells, that separating the hRPE cells, mixing uniformly to prepare single cell suspension; (2), hRPE cell cultivation and generation that digests original cultivation liquid, ending digestion, blowing and beating to form cell suspension, eccentrically filtering and removing the upper clear liquid, adding cultivating substrate, to disperse and form cell suspension, filtering with cell screen, transferring cell into cultivating bottle, generating to at least fifth generation; (3), adding common salt into hRPE nerve stem cell, to prepare cell suspension injection.

The invention discloses application of kaempferol to preparation of a medicament for preventing and treating retina injury diseases. The kaempferol exists in a plurality of edible plants (including fruits, vegetables and beans) and traditional Chinese medicine (chrysanthemum, raspberry, semen cuscutae, radix astragali seu hedysari and ginkgo leaf). The protective effect of the kaempferol on human retinal pigment epithelial cells (ARPE-19) suffering from oxidative stress injury induced by hydrogen peroxide (H2O2) is observed, and the expression change of molecules of the kaempferol relevant to apoptosis after the retinal pigment epithelial cells are treated by H2O2 is observed in order to discuss the anti-apoptotic effect of the kaempferol on the retinal pigment epithelial cells suffering from oxidative injury and the molecular mechanism of the kaempferol, so that a theoretical basis is laid for the prevention and treatment of eye diseases relevant to retinal pigment epithelial cell injury through the kaempferol.

An object of the present invention is to find a novel medicinal use of 2-phenyl-1,2-benzisoselenazol-3(2H)-one or a salt thereof. 2-Phenyl-1,2-benzisoselenazol-3(2H)-one or a salt thereof exhibits an excellent inhibitory effect on neovascularization in the choroid and also has a protective effect on retinal pigment epithelial cell damage, and therefore is useful as a prophylactic or therapeutic agent for age-related macular degeneration.

The present invention provides a method of purifying highly pure retinal pigment epithelial cells from a cell population obtained by induction of differentiation of pluripotent stem cells into retinal pigment epithelial cells, by a simple and easy operation in a short period. The purification method of the present invention includes a step of introducing a cell population containing retinal pigment epithelial cells obtained by differentiation induction of pluripotent stem cells on laminin or a fragment thereof on a filter, and obtaining a cell population that passed the filter.

The present invention provides a method of producing a cell sheet including the following steps(1) seeding and culturing retinal pigment epithelial cells on a collagen gel to form a cell sheet composed of the retinal pigment epithelial cells, and(2) degrading the collagen gel with collagenase to detach the cell sheet composed of the retinal pigment epithelial cells, and the like.

Methods of stabilizing and organizing collagen fibrils in extracellular matrix of retinal tissues, particularly Bruch's membranes, and stabilizing retinal pigment epithelial layers lining Bruch's membrane are disclosed. The stabilization and organization may be effected by treating retinal tissues with a protein that crosslinks and organizes collagen fibrils, such as decorin. The stabilization and organization methods include treatment of retinal tissues before, during, or after diagnosis of dry macular degeneration, diagnosis of early stages of diabetic retinopathy and diabetic macular edema to prevent, retard, or limit progression of disorganization of Bruch's membrane and disorganization of retinal pigment epithelial cells lining Bruch's membrane.

The invention relates to a method for transdifferentiation of human fibroblast to retinal pigment epithelium. The method comprises the steps of transferring various transcriptional regulation factors and reporter genes into mammal fibroblast, and then, culturing the fibroblast with various culturing mediums to obtain the retinal pigment epithelium.

Provided are a production method of retinal pigment epithelial (RPE) cells that improves differentiation induction efficiency of pluripotent stem cells into RPE cells, and can provide highly pure RPE cells by a simple and easy operation in a short period, a culture method of RPE cells that can stably grow and culture a cell, a toxicity / efficacy evaluation method using RPE cells useful for transplantation therapy, and a therapeutic drug for a retinal disease. The invention relates to a production method of RPE cells, comprising adhesion culture of human pluripotent stem cells using a culture substrate coated with a laminin-E8 fragment, a culture method of RPE cells, comprising adhesion culture of RPE cells using a culture substrate coated with a laminin-E8 fragment, a toxicity or efficacy evaluation method using RPE cells obtained by producing or culturing by the method, and a therapeutic drug for a retinal disease, containing the RPE cells.

A method of selecting retinal pigmented epithelial (RPE) cells from a mixed population of cells is disclosed. The method comprises:(a) analyzing the cells of the mixed population of cells for at least one of the following parameters:(i) cells which autofluorescence above a predetermined threshold;(ii) cells which express CD81 above a predetermined threshold; and(iii) cells which scatter light perpendicular to a laser beam above a predetermined threshold; and(b) selecting cells which are positive for at least one of the parameters, thereby sorting RPE cells from a mixed population of cells.

The invention provides a separation culture method of human fetal retinal pigment epithelial cells, relating to a method for separating fRPE (fetal retinal pigment epithelial) cells by utilizing a mechanical method and performing in-vitro culture. The separation culture method of the human fetal retinal pigment epithelial cells, provided by the invention, provides a new source for in-vitro culture, amplification of RPE (retinal pigment epithelial) cells and treatment of AMD (age-related macular degeneration) and other diseases with RPE injuries.

The invention relates to a method for preparing a retinal pigment epithelial cell slice by using an autologous immunocyte, which comprises the following steps of: S1, obtaining an autologous immunocyte from the peripheral blood of a patient, and differentiating the immunocyte, in vitro, to a multifunctional induction stem cell; S2, directionally inducing the multifunctional induction stem cell obtained in S1 to generate a retinal pigment epithelial cell, so as to obtain a retinal pigment epithelial cell slice. The used RPE is derived from the autologous immunocyte of the patient and then the PRE is transplanted to the same patient, thus reducing the immune rejection of the patient. Besides, no problems of organization matching and ethic exist; therefore, the ethical and post-operative results of the test are not obstacles to carrying out such clinical trials. Moreover, the method has a good prospect on the treatment of macular degeneration.