Method for transplanting cells into the brain and therapeutic uses therefor

• US 6,264,943 B1
• Filed: 12/10/1999
• Issued: 07/24/2001
• Est. Priority Date: 10/19/1990
• Status: Expired due to Fees

• Current Assignee: New York University
• Original Assignee: New York University
• Inventors: Cherksey, Bruce D.
• Primary Examiner(s): Clark, Deborah J. R.
• Assistant Examiner(s): Sorbello, Eleanor
• Application Number:
  US09/467,549
• Time in Patent Office: 592 Days
• Field of Search: 424/93.7, 424/93.21, 424/93.1, 435/174, 435/176
• US Class Current: 424/93.7
• CPC Class Codes: A61F 2/00 Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents as cosmetic articles, see the relevant subclasses, e.g. wigs, hair pieces, A41G3/00, A41G5/00; artificial nails A45D31/00; dental prostheses A61C13/00; materials for prostheses A61L27/00; artificial hearts A61M60/00; artificial kidneys A61M1/14
• CPC Class Codes: A61K 35/30 Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
• CPC Class Codes: A61K 47/6923 the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 9/0085 Brain, e.g. brain implants; Spinal cord
• CPC Class Codes: A61K 9/1676 having a drug-free core with discrete complete coating layer containing drug adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921
• CPC Class Codes: A61L 27/3804 characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
• CPC Class Codes: A61L 27/3813 Epithelial cells, e.g. keratinocytes, urothelial cells
• CPC Class Codes: A61L 27/3821 Bone-forming cells, e.g. osteoblasts, osteocytes, osteoprogenitor cells
• CPC Class Codes: A61L 27/383 Nerve cells, e.g. dendritic cells, Schwann cells
• CPC Class Codes: A61L 27/3878 Nerve tissue, brain, spinal cord, nerves, dura mater
• CPC Class Codes: C12N 2502/08 cells of the nervous system
• CPC Class Codes: C12N 2531/00 Microcarriers
• CPC Class Codes: C12N 2533/12 Glass
• CPC Class Codes: C12N 5/0614 Adrenal gland
• CPC Class Codes: C12N 5/0618 Cells of the nervous system
• CPC Class Codes: C12N 5/0619 Neurons
• CPC Class Codes: C12N 5/0621 Eye cells, e.g. cornea, iris pigmented cells photoreceptors C12N5/062

Abstract

A method for grafting a cell in the brain of a mammalian subject is accomplished by attaching the cell to a support matrix so that the cell attaches to the matrix surface, and implanting the support matrix with the attached cell into the brain. Preferred support matrices are glass or plastic microbeads, either solid or porous, having a diameter from about 90 to about 125 μm. The method employs cells of different types, preferably cells of neural or paraneural origin, such as adrenal chromaffin cells. Also useful are cell lines grown in vitro. Cells not of neural or paraneural origin, such as fibroblasts, may also be used following genetic alteration to express a desired neural product such as a neurotransmitter or a neuronal growth factor. The method is used to treat neurological diseases such as Parkinson'"'"'s disease, Alzheimer'"'"'s disease, Huntington'"'"'s disease, epilepsy, and traumatic brain injury.

Claims

1. A method for increasing the viability of viable human retinal pigment epithelial (hRPE) cells which are injected into a mammalian brain or spinal cord, comprising:

adhering viable hRPE cells to the surface of a gelatin-containing support matrix, and

injecting the adhered HRPE cells into a mammalian brain or spinal cord;

whereby the injected cells remain viable for at least two months after said injection.

2. The method of claim 1 wherein said human RPE cells are human RPE cell line cells.

3. The method of claim 1 wherein said gelatin-containing support matrix is a gelatin-containing microcarrier bead.

4. The method of claim 3 wherein said microcarrier bead has a diameter of from about 90 μ

m to about 150 μ

m.

5. The method of claim 1 wherein said injected HRPE cells remain viable for at least 180 days after said injection.

6. A syringe containing therein viable human retinal pigment epithelial (HRPE) cells that are adhered to the surface of a gelatin-containing support matrix.

7. The syringe of claim 6, wherein said hRPE cells are hRPE cell line cells.

8. The syringe of claim 6, wherein said gelatin-containing support matrix is gelatin-containing microcarriers.

9. A method for providing a neurally-active molecule to a mammal comprising

introducing a multiplicity of gelatin-containing supports containing an effective number of viable human retinal pigment epithelial (hRPE) cells adhered to surfaces of the supports, wherein:

the introducing is into the mammal'"'"'s brain or spinal cord;

the supports have diameters greater than 10 μ

m; and

said cells provide said neurally active molecule for at least two months after said administration.

10. The method of claim 9, wherein said HRPE cells are hRPE cell line cells.

11. The method of claim 9, wherein said HRPE cells supply said neurally active substance.

12. A method for providing dopamine to a mammal comprising injecting a multiplicity of gelatin-containing supports containing a population of viable human retinal pigment epithelial (hRPE) cells adhered to surfaces of the supports, wherein the population provides an effective amount of dopamine and wherein:

the injecting is into the mammal'"'"'s brain or spinal cord; and

the supports have diameters greater than 10 μ

m.

13. The method of claim 12, wherein said HRPE cells are hRPE cell line cells.

14. A method for treating Parkinson'"'"'s disease, comprising:

injecting a multiplicity of gelatin-containing supports containing a population of viable human retinal pigment epithelial (hRPE) cells adhered to surfaces of the supports, into a human suffering from Parkinson'"'"'s disease, wherein the population provides an effective amount of dopamine and wherein;

the injecting is into the human'"'"'s brain; and

the supports have diameters greater than 10 μ

m.

15. The method of claim 14, wherein said hRPE cells are HRPE cell line cells.