Method for implanting encapsulated cells in a host

• US 5,550,050 A
• Filed: 04/15/1994
• Issued: 08/27/1996
• Est. Priority Date: 04/15/1994
• Status: Expired due to Term

• Current Assignee: Neurotech USA, Inc. (Woodbrook Group Holdings, Inc.)
• Original Assignee: Cytotherapeutics, Inc.
• Inventors: Rudnick, Seth A., Dionne, Keith E., Lysaght, Michael J., Hammang, Joseph P., Holland, Laura M.
• Primary Examiner(s): Rollins, John W.
• Application Number:
  US08/228,403
• Time in Patent Office: 865 Days
• Field of Search: 434/240.2, 434/240.22, 434/245, 434/244
• US Class Current: 435/382
• CPC Class Codes: A61K 35/13 Tumour cells, irrespective of tissue of origin tumour vaccines A61K39/00
• CPC Class Codes: A61K 35/22 Urine; Urinary tract, e.g. kidney or bladder; Intraglomerular mesangial cells; Renal mesenchymal cells; Adrenal gland
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• 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 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/0085 Brain, e.g. brain implants; Spinal cord
• CPC Class Codes: A61K 9/0092 Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: C07K 14/475 Growth factors; Growth regulators
• CPC Class Codes: C07K 14/48 Nerve growth factor [NGF]
• CPC Class Codes: C12N 2500/02 Atmosphere, e.g. low oxygen conditions
• CPC Class Codes: C12N 2500/34 Sugars
• CPC Class Codes: C12N 5/0614 Adrenal gland
• CPC Class Codes: C12N 5/0618 Cells of the nervous system

Abstract

This invention provides methods for implanting encapsulated cells in a host comprising exposing cells to restrictive conditions for a sufficient period of time to establish a desired cell property in response to the restrictive conditions and implanting the encapsulated cells in a host, the cell property being substantially maintained following implantation. Also provided are cells produced by exposure to restrictive conditions.

Claims

1. A method for preparing encapsulated cells for implanting at an implantation site in a human comprising the steps of:

(a) encapsulating the cells in a biocompatible capsule, and

(b) exposing the cells to at least one restrictive condition that closely matches a condition at the implantation site and which establishes a measurable change in at least one cell property in response to the restrictive condition.

2. The method of claim 1 wherein the encapsulated cells are exposed to the restrictive condition in vitro.

3. The method of claim 1 wherein the encapsulated cells are exposed to the restrictive condition in vivo by implantation at an implantation site in a recipient prior to implantation at an implantation site in a human.

4. The method of claim 1 wherein the cells are xenogeneic to the host and the capsule is immunoisolatory.

5. The method of claim 1 wherein at least one restrictive condition is a glucose concentration ranging from about 40 mg/deciliter to about 70 mg/deciliter.

6. The method of claim 1 wherein at least one restrictive condition is an oxygen concentration ranging from about 40 mmHg to about 65 mmHg.

7. The method of claim 3 wherein the cells are selected from the group consisting of adrenal chromaffin cells, baby hamster kidney cells, and PC12 cells.

8. The method of claim 7 wherein the cells are adrenal chromaffin cells and are implanted in a recipient for 4 months or longer.

9. The method of claim 7 wherein the cells are PC12 cells and are implanted in a recipient for 6 months or longer.

10. The method of claim 1 wherein the cells produce a biologically active molecule selected from the group consisting of neurotransmitters, analgesics and growth factors.

11. The method of claim 1 wherein the capsule is implanted in a host at an implantation site selected from the group consisting of cerebrospinal fluid or brain parenchyma.

12. The method of claim 1 wherein the host is a human.

13. A method for preparing encapsulated cells for implanting at an implantation site in a xenogeneic host comprising the steps of:

(a) culturing the cells under at least two restrictive conditions, and

(b) encapsulating the cells in a biocompatible capsule and further exposing the encapsulated cells to at least one restrictive condition that closely matches a condition at the implantation site and which establishes a measurable change in at least one cell property in response to the restrictive condition.