Cell-embedded vascular graft for transplantation
Disclosed herein is a transplantation graft for transplanting cells into a patient. In an aspect, the graft may include a first graft layer having a generally cylindrical configuration defining a lumen therethrough, a coating layer surrounding the first graft layer, and a plurality of cells or vectors implanted in either the first graft layer or the coating layer. Further disclosed herein is a method for transplanting cells into a patient and a method of treating a patient in need thereof. The transplantation graft may be implanted in the patient in an arteriovenous configuration and the coating layer protects the implanted cells from the patient's immune system. The plurality of cells in the transplantation graft may release a biologically active agent in response to a biological factor in blood flowing through the lumen of the transplantation graft.
1 . A transplantation graft for transplanting cells into a patient, the graft comprising:
a first graft layer having a generally cylindrical configuration and defining a lumen configured to receive a blood flow of the patient directly therethrough, wherein the first graft layer directly contacts the blood flow within the lumen;
a non-alginate coating layer surrounding the first graft layer; and
a plurality of implanted cells encapsulated within a plurality of alginate microbeads imbedded within either the first graft layer or the non-alginate coating layer,
wherein the transplantation graft is configured to be implanted in the patient in an arteriovenous configuration, and
wherein the non-alginate coating layer protects the implanted cells from the patient's immune system.
2 . The transplantation graft of claim 1 , wherein the plurality of cells in the transplantation graft release a biologically active agent in response to a biological factor in blood flowing through the lumen of the transplantation graft.
3 . The transplantation graft of claim 1 further comprising a non-alginate second graft layer between the first graft layer and the non-alginate coating layer.
4 . The transplantation graft of claim 3 , wherein the first graft layer, the non-alginate second graft layer, and any combination thereof is porous or microporous.
5 . The transplantation device of claim 3 , wherein the second graft layer comprises polytetrafluoroethylene (PTFE), expanded PTFE (ePTFE), stretch PTFE, polyethylene terephthalate, polyurethaneurea, polydimethylsiloxane (PDMS), or combinations thereof.
6 . The transplantation graft of claim 1 , wherein the implanted cells are within the first graft layer.
7 . The transplantation graft of claim 1 , wherein the implanted cells are within the non-alginate coating layer.
8 . The transplantation device of claim 1 , wherein the first graft layer comprises polytetrafluoroethylene (PTFE), expanded PTFE (ePTFE), stretch PTFE, polyethylene terephthalate, polyurethaneurea, polydimethylsiloxane (PDMS), or combinations thereof.
9 . The transplantation device of claim 1 , wherein the non-alginate coating layer comprises, polyethylene glycol (PEG), PTFE, polyglycolic acid (PGA), poly-l-lactic acid (PLLA), polyhydroxyalkanoate, polycaprolactone-copolylactic acid, polylactide-coglycolide (PLGA), PDMS, polycaprolactone, or combinations thereof.
10 . The transplantation device of claim 9 , wherein the coating layer consists of PEG.
11 . The transplantation device of claim 1 , wherein the implanted cells are selected from the group consisting of primary cells, pluripotent stem cells, differentiated stem cells, pancreatic cells, islet cells, β cells, thyroid cells, parathyroid cells, pituitary gland cells, adrenal gland cells, liver cells, genetically engineered cells, and any cell which secretes a biologically active agent.
12 . A method for transplanting cells into a patient comprising:
providing a transplantation graft comprising:
a first graft layer having a generally cylindrical configuration and defining a lumen configured to receive a blood flow of the patient directly therethrough, wherein the first graft layer directly contacts the blood flow within the lumen;
a non-alginate coating layer surrounding the first graft layer; and
a plurality of implanted cells encapsulated within a plurality of alginate microbeads imbedded within either the first graft layer or the non-alginate coating layer, wherein the transplantation graft is implanted in the patient in an arteriovenous configuration, and the non-alginate coating layer protects the implanted cells from the patient's immune system;
implanting the plurality of cells into the first graft layer or the non-alginate coating layer of the transplantation graft; and
implanting the transplantation graft into the patient in an arteriovenous configuration.
13 . The method of claim 12 , wherein the plurality of implanted cells are implanted in the transplantation graft after the transplantation graft has been implanted in the patient.
14 . A method of treating a patient in need thereof, comprising,
implanting a transplantation graft comprising:
a first graft layer having a generally cylindrical configuration and defining a lumen configured to receive a blood flow of the patient therethrough, wherein the first graft layer directly contacts the blood flow within the lumen;
a non-alginate coating layer surrounding the first graft layer; and
a plurality of implanted cells encapsulated within a plurality of alginate microbeads imbedded within either the first graft layer or the non-alginate coating layer, into the patient in an arteriovenous configuration, wherein the non-alginate coating layer protects the implanted cells from the patient's immune system;
wherein the plurality of implanted cells in the transplantation graft release a biologically active agent in response to a biological factor in blood flowing through the lumen of the transplantation graft.
15 . The method of claim 14 , wherein the implanted cells are selected from the group consisting of primary cells, pluripotent stem cells, differentiated stem cells, pancreatic cells, islet cells, β cells, thyroid cells, parathyroid cells, pituitary gland cells, adrenal gland cells, liver cells, genetically engineered cells, and any cell which secretes a biologically active agent.
16 . The method of claim 14 , wherein the implanted cells are stem cell derived β cells.
17 . The method of claim 14 , wherein the biological factor is selected from the group consisting of proteins, peptides, carbohydrates, polysaccharides, and any factor within the blood.
18 . The method of claim 17 , wherein the biological factor is glucose.
19 . The method of claim 14 , wherein the biologically active agent is selected from the group consisting of proteins, peptides, hormones, enzymes, and proteases.
20 . The method of claim 19 , wherein the biologically active agent is insulin.