Methods and devices for cellular transplantation

• US 10,207,026 B2
• Filed: 02/18/2015
• Issued: 02/19/2019
• 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): Barron, Sean C.
• Application Number:
  US14/625,135
• Publication Number:
  US 20150209479A1
• Time in Patent Office: 1,462 Days
• Field of Search: None
• 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 an immunologically-compatible polymer 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 plug configured to be positioned within the lumen of the at least one chamber,

wherein the plug 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 device comprises cells within the chamber.

3. The device of claim 2, wherein the cells comprise islets of Langerhans.

4. The device of claim 2, wherein the cells comprise islets of Langerhans and Sertoli cells.

5. The device of claim 2, wherein the cells comprise stem cells.

6. The device of claim 2, wherein the cells comprise one or more of stem cells, differentiated stem cells, neural stem cells, dopaminergic neurons, cord blood cells, embryonic stem cells, and/or mesenchymal stem cells.

7. The device of claim 2, wherein the cells comprise allogeneic, xenogenic, or syngeneic donor cells, or patient-derived cells.

8. The device of claim 2, wherein the cells comprise genetically engineered cells or cell lines.

9. The device of claim 1, wherein the porous scaffold comprises multiple chambers that are connected laterally.

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

11. The device of claim 1, further comprising a material coating at least a part of the porous scaffold, wherein the material stimulates tissue incorporation and angiogenesis.

12. The device of claim 11, wherein the material comprises one or more of a growth factor, an antifibrotic agent, a polymer, vascular endothelial growth factor (VEGF), collagen, fibronectin, polyethylene-imine and dextran sulfate, polyvinyl siloxane and polyethyleneimine, phosphorylcholine, poly(ethylene glycol), poly(lactic-co-glycolic acid), poly(lactic acid), polyhydroxyvalerate and copolymers, polyhydroxybutyrate and copolymers, polydiaxanone, polyanhydrides, poly(amino acids), poly(orthoesters), gelatin, a cellulose polymer, a chitosan, an alginate, vinculin, agar, agarose, hyaluronic acid, and matrigel.

13. 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 plug in a neovascularized collagen matrix, and wherein the plug is capable of being withdrawn from the chamber to create a space within the chamber that is encapsulated in the neovascularized collagen matrix.

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

15. 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.

16. The device of claim 2, wherein the cells comprise differentiated stem cells or encapsulated cells.

17. The device of claim 16, wherein the cells are encapsulated in alginate, a polysaccharide hydrogel, chitosan, calcium or barium alginate, a layered matrix of alginate and polylysine, photopolymerizable poly(ethylene glycol) polymer, a polyacrylate, hydroxyethyl methacrylate, methyl methacrylate, a silicon capsule, a silicon nanocapsule, a polymembrane, or acrylonitrile-co-vinyl chloride.

18. The device of claim 2, wherein the cells comprise two or more cell types selected from islets of Langerhans, Sertoli cells, stem cells, differentiated stem cells, neural stem cells, dopaminergic neurons, cord blood cells, embryonic stem cells, allogeneic cells, xenogeneic or syngeneic cells, genetically engineered cells or cell lines, and mesenchymal stem cells.

19. The device of claim 11, wherein the material comprises a biocompatible, biodegradable material, a non-biodegradable material, or a combination thereof.

20. The device of claim 1, further comprising a material coating at least a part of the porous scaffold, wherein the material comprises a biocompatible, biodegradable material, a non-biodegradable material, or combination thereof.

21. The device of claim 1, wherein the polymer mesh comprises a polytetrafluoroethylene mesh, a polyurethane mesh, a polyester mesh, and/or a silk mesh.

22. The device of claim 1, wherein the polymer mesh comprises a polypropylene mesh.

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

a. implanting the device of claim 1 in the host body;

b. maintaining the 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 plug;

e. inserting a cell infusion tube into the chamber of the device;

f. infusing the chamber with cells; and

g. reclosing the at least one seal.

24. The method according to claim 23, further comprising the step of imaging the porous scaffold prior to delivering cells.

25. The method according to claim 23, wherein the cells comprise islets of Langerhans.

26. The method according to claim 23, wherein the cells comprise islets of Langerhans and Sertoli cells.

27. The method according to claim 23, wherein the cells comprise stem cells.

28. The method according to claim 23, wherein the cells comprise neural stem cells, dopaminergic neurons, cord blood cells, embryonic stem cells, or mesenchymal stem cells.

29. The method according to claim 23, wherein the cells comprise allogeneic, xenogenic, or syngeneic donor cells, or patient-derived cells.

30. The method according to claim 23, wherein the cells comprise genetically engineered cells or cell lines.

31. The method according to claim 23, wherein the cells comprise differentiated stem cells or encapsulated cells.

32. The method according to claim 31, wherein the cells are encapsulated in alginate, a polysaccharide hydrogel, chitosan, calcium or barium alginate, a layered matrix of alginate and polylysine, photopolymerizable poly(ethylene glycol) polymer, a polyacrylate, hydroxyethyl methacrylate, methyl methacrylate, a silicon capsule, a silicon nanocapsule, a polymembrane, or acrylonitrile-co-vinyl chloride.

33. The method of claim 23, wherein the cells comprise two or more cell types selected from islets of Langerhans, Sertoli cells, stem cells, differentiated stem cells, neural stem cells, dopaminergic neurons, cord blood cells, embryonic stem cells, allogeneic cells, xenogeneic or syngeneic cells, genetically engineered cells or cell lines, and mesenchymal stem cells.