Microfabricated tissue as a substrate for pigment epithelium transplantation

Inactive Publication Date: 2005-02-03
THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0029] The present invention is directed to methods and related products for treating retinal diseases such as AMD, RP, and other retinal diseases. For example, one therapy for AMD is to transplant suspensions of either retinal pigment epithelial (RPE) cells, iris pigment epithelial (IPE) cells, stem cells, or other cells, to rescue the diseased retina. The present invention provides novel tissue engineering techniques to precision engineer autologous human tissues (e.g., human lens capsule) as a substrate for transplanting cells, such as IPE cells, RPE cells, stem cells, and other cells. Transplanted pigment epithelium cells grown on the modified tissue and substrates of the invention are able to grow to high density and to exhibit

Problems solved by technology

Bruch's membrane is also thought to be damaged; such damage may be the initiating stimulus for RPE demise.
Damage to Bruch's membrane, which may occur due to accumulation of waste products from outer segment metabolism, for example, prevents the exchange of oxygen, growth factors and waste products.
Such impaired exchange leads to hypoxia in the photoreceptors.
However, such approaches have not met with great success.
However, this approach has not succeeded in the past, due in part to the failure of the transplanted cells to function properly and in part due to rejection of the cells by the host animals.
However, challenges to both IPE and RPE transplantation methods include i) difficul

Method used

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  • Microfabricated tissue as a substrate for pigment epithelium transplantation
  • Microfabricated tissue as a substrate for pigment epithelium transplantation
  • Microfabricated tissue as a substrate for pigment epithelium transplantation

Examples

Experimental program
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Example

EXAMPLE 1

[0111] Microcontact printing was used to deposit micron-sized patterns of biomolecules onto lens capsule tissue. Poly(dimethyl siloxane) (PDMS) stamps were cast from masters containing a topological pattern of grid lines spaced 50 microns apart. The PDMS stamp was made from a master that was microfabricated from a silicon wafer. PDMS stamps were used to microfabricate patterns onto lens capsule tissue. Shown in FIG. 2 is a scanning electron micrograph (SEM) of a PDMS stamp used to deposit a micropattern onto a piece of human lens capsule tissue.

[0112] The PDMS stamp shown in FIG. 2 has a surface topology given by a hexagonal array of 5 μm-wide lines. Each line is separated by approximately 50 μm. FIG. 3 shows a human lens capsule stamped with the PDMS stamp shown in FIG. 2. The PDMS stamp was used to deposit hexagonal patterns of a PVA and fluorescein solution (2% PVA and 0.1 mg / mL fluorescein) onto the lens capsule. This example shows that the stamp is effective to produ...

Example

EXAMPLE 2

[0113] A SEM of a PDMS stamp with circular patterns used for micropatterning tissue is shown in FIG. 4. As shown, the stamp has a surface topology given by an array of circular wells of approximately 50 μm in diameter. When the relief pattern is coated with an inhibitory molecule, such as PVA or mucilage, and the stamp applied to a lens capsule, the inhibitory molecules are transferred to the lens capsule in the pattern shown. FIG. 5 shows the surface of a lens capsule that has been patterned with a PDMS stamp having a pattern as shown in FIG. 2 and RPE cells grown on it. This example shows that the stamp is effective to place a pattern on the lens capsule surface that corresponds to the pattern of the stamp, and for cell growth to be patterned according to the pattern of the stamp.

[0114] Thus, application of the stamps of the invention are able to deposit inhibitory molecules in patterns that can direct the growth of cells growing on a patterned substrate. Because the le...

Example

EXAMPLE 3

[0115] Masking of the surface of lens capsule tissue and then irradiating the exposed surface, but not the masked surface, with UV radiation is accomplished by placement of a SEM grid onto the surface of lens capsule tissue. A SEM grid with spacing of 50 microns is placed onto the exposed surface of an excised lens capsule tissue resting on a glass coverslip immersed in phosphate-buffered saline. The surface of the lens capsule tissue and the SEM grid are not immersed in the phosphate-buffered saline, but rise above the level of the phosphate-buffered saline. UV light is directed onto the exposed surface of the lens capsule tissue effective to irradiate the lens capsule tissue not resting immediately below the SEM grid material. After irradiation, the SEM grid is removed. The lens capsule surface has a micropattern of lines including tissue not irradiated (regions under SEM grid material) enclosing regions comprising irradiated tissue.

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Abstract

An ocular implant is provided with a substrate and a membranous tissue layer secured to the substrate. Cells such as IPE cells, RPE cells and stem cells are attached on the surface of the membranous tissue layer either in situ or in vivo through cells transplantation. The cells are separated into regions on the surface by creating a pattern on the surface enclosing regions for receiving the cells. The substrate is a bioabsorbable and/or polymeric substrate. Examples of membranous tissue layer are lens capsule, inner limiting membrane, corneal tissue, Bruch's membrane tissue, amniotic membrane tissue, serosal membrane tissue, mucosal membrane tissue and neurological tissue. The membranous tissue layer could have a micropattern of biomolecules. A microfluidic network could be placed onto the microfabricated membranous tissue layer.

Description

FIELD OF THE INVENTION [0001] The present invention relates generally to the field of treatment of eye disorders, in particular retinal disorders such as age-related macular degeneration, retinitis pigmentosa, and other retinal diseases. In addition, the invention relates to methods and apparatus for modifying tissues, and for the transplantation of cells and tissues. BACKGROUND OF THE INVENTION [0002] Diseases of the retina, such as age-related macular degeneration (AMD), retinitis pigmentosa (RP), and other diseases, are the leading cause of severe visual impairment or blindness in the industrialized world. One hallmark of AMD, as in RP, is the degeneration and loss of cells of the retinal pigment epithelium (RPE). Bruch's membrane is also thought to be damaged; such damage may be the initiating stimulus for RPE demise. RPE cells are vital to the survival and proper functioning of retinal photoreceptors, which are the only cells in the eye which directly sense light. RPE degenerat...

Claims

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Application Information

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IPC IPC(8): C12M3/00A61F2/14A61L27/00A61L27/38C12N5/07C12N5/074
CPCA61F2/14A61L27/3839A61L27/3813A61L27/3604
Inventor FISHMAN, HARVEY A.BLUMENKRANZ, MARKBENT, STACEY F.LEE, CHRISTINAHUIE, PHILIP JR.PALANKER, DANIEL V.
Owner THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
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