Methods and devices for cellular transplantation

• US 9,011,899 B2
• Filed: 08/27/2010
• Issued: 04/21/2015
• Est. Priority Date: 08/28/2009
• Status: Active Grant

• Current Assignee: Sernova Corporation
• Original Assignee: Sernova Corporation
• Inventors: Hasilo, Craig, Leushner, Justin, Haworth, Daniel Nicholas, Shohet, Simon, Toleikis, Philip Michael, Siroen, Delfina Maria Mazzuca
• Primary Examiner(s): DRISCOLL, LORA E BARNHART
• Application Number:
  US13/393,038
• Publication Number:
  US 20120245705A1
• Time in Patent Office: 1,698 Days
• Field of Search: None
• US Class Current: 424/424
• CPC Class Codes: A61F 2/022 Artificial gland structures using bioreactors hemodialysis A61M1/16; hemofiltration A61M1/34; other extracorporeal blood treatment A61M1/36
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61L 2300/64 Animal cells
• CPC Class Codes: A61L 2400/18 Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
• CPC Class Codes: A61L 2420/00 Materials or methods for coatings medical devices
• CPC Class Codes: A61L 27/16 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• 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 27/3834 Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: A61L 27/3886 comprising two or more cell types
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: A61M 2039/0282 with implanted tubes connected to the port
• CPC Class Codes: A61M 39/0247 Semi-permanent or permanent transcutaneous or percutaneous access sites to the inside of the body peritoneal dialysis catheters A61M1/285; tracheostomy devices A61M16/0465; measuring pressure within the body A61B5/03; colostomy devices A61F5/445; gastrotomy feeding tubes A61J15/0015; means for fixing a feeding tube outside of the body A61J15/0053
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C08L 23/12 Polypropene
• CPC Class Codes: C12N 2533/30 Synthetic polymers thermoreactive polymers, e.g. PNIPAm, C12N2539/10
• CPC Class Codes: C12N 5/0677 Three-dimensional culture, tissue culture or organ culture; Encapsulated cells

Abstract

Devices and methods for transplanting cells in a host body are described. The cell comprises a porous scaffold that allows ingrowth of vascular and connective tissues, a plug or plug system configured for placement within the porous scaffold, and a seal configured to enclose a proximal opening in the porous scaffold. The device may further comprise a cell delivery device for delivering cells into the porous scaffold. The method of cell transplantation comprises a two step process. The device is incubated in the host body to form a vascularized collagen matrix around a plug positioned within the porous scaffold. The plug is then retracted from the porous scaffold, and cells are delivered into the vascularized space created within the porous scaffold.

Claims

1. A device for implanting cells in a host body, comprising:

a porous scaffold comprising a polypropylene mesh forming the walls of at least one chamber,

wherein the chamber comprises an opening at either or both of a proximal end and a distal end of the chamber,

wherein the proximal end and the distal end are separated by a lumen that is bounded by the walls, and

wherein the porous scaffold has pores sized to facilitate growth of vascular and connective tissues around and through the walls of the at least one chamber;

at least one removable, non-porous two-plug system configured to be positioned within the lumen of the at least one chamber;

wherein the two-plug system comprises an outer plug configured to be positioned within the lumen of the at least one chamber and an inner plug configured to be positioned within the outer plug, and

wherein the two-plug system extends along the lumen of the chamber; and

at least one seal configured to enclose either or both the proximal end and the distal end of the chamber.

2. The device of claim 1, wherein the porous scaffold comprises multiple chambers that are connected laterally and optionally comprising a common seal for the multiple chambers.

3. The device of claim 1, wherein the at least one seal is a polymer film that is ultrasonically welded to the porous scaffold.

4. The device of claim 1, wherein the outer plug and the inner plug comprise complementary sealing mechanisms.

5. The device of claim 1, wherein the inner wall of the outer plug comprises at least one protrusion along the length of the outer plug.

6. The device of claim 1, wherein the porous scaffold is configured to facilitate growth of vascular and connective tissues into the porous chamber to encapsulate the two-plug system in a neovascularized collagen matrix, and wherein the two-plug system is capable of being withdrawn from the chamber to create a space within the chamber that is encapsulated in the neovascularized collagen matrix.

7. The device of claim 1, further comprising a cell delivery device comprising at least one cell infusion tube configured to be positioned within the outer plug and configured to deliver cells to the chamber of the device.

8. The device of claim 1, wherein the cell delivery device further comprises a connector configured to connect to the outer plug when the at least one cell infusion tube is inserted into the outer plug and optionally wherein the connector comprises a clip for connecting to the outer plug and optionally wherein attachment of the connector to the outer plug allows the connector and the outer plug to be retracted from the device as a single unit.

9. The device of claim 1, wherein the porous scaffold comprises one chamber, two chambers, three chambers, four chambers, five chambers, six chambers, seven chambers, eight chambers, ten chambers, twelve chambers, or more chambers.

10. A method for transplanting cells into a host body comprising:

a. implanting a device according to claim 1 in the host body;

b. maintaining said device in the host body until the device is infiltrated with vascular and connective tissues;

c. accessing the implanted device and opening the at least one seal;

d. withdrawing the inner plug from the two-plug system;

e. inserting a cell infusion tube into the outer plug;

f. withdrawing the outer plug from the at least one chamber and infusing the chamber with cells; and

g. reclosing the at least one seal.

11. The method according to claim 10, further comprising the step of imaging the porous scaffold prior to delivering cells.

12. The method according to claim 10, wherein the cells comprise one or more of islets of Langerhans cells, Sertoli cells, mesenchymal stem cells, or stem cells, or a combination thereof.

13. The method according to claim 10, wherein the cells comprise allogeneic, xenogenic, or syngeneic donor cells.

14. The method according to claim 10, wherein the cells comprise genetically engineered cells or cell lines.

15. The method according to claim 10, wherein the cells comprise islets of Langerhans and Sertoli cells.

16. The device of claim 1, wherein the device comprises cells within the chamber.

17. The device of claim 16, wherein the cells comprise islets of Langerhans and Sertoli cells.

18. The device of claim 16, wherein the cells comprise stem cells.

19. The device of claim 16, wherein the cells comprise dopaminergic neurons or neural stem cells.