Thin film cell encapsulation devices
Thin film devices, e.g., multilayer thin film devices, that encapsulate cells for transplantation into a subject are provided. Also provided are methods of using and methods of preparing the subject devices. The thin film devices include a first porous polymer layer and a second porous polymer layer that define a lumen therebetween and encapsulate a population of cells within the lumen. The thin film devices can promote vascularization into the lumen of the device via the pores in the first polymer layer and/or second polymer layer; limit foreign body response to the device; limit ingress of cells, immunoglobulins, and cytokines into the lumen via the first and the second polymer layers; and release from the first polymer layer and/or the second polymer layer molecules secreted by the population of cells.
1 . A method for transplanting cells into a subject in need thereof, said method comprising:
(a) providing a thin film device comprising:
(i) a first nanoporous or microporous polymer layer;
a second nanoporous or microporous polymer layer, wherein said first and second nanoporous or microporous polymer layers define a lumen between said first and second nanoporous or microporous polymer layers; and
(iii) a therapeutically effective amount of a population of cells disposed in said lumen between said first and second nanoporous or microporous polymer layers, wherein said first nanoporous or microporous polymer layer has a thickness of 10 μm to 100 μm and said second nanoporous or microporous polymer layer has a thickness of 10 μm to 100 μm, and
wherein said device has a surface area of 1 cm 2 to 5 cm 2 ; and
(b) transplanting said device into said subject, wherein one or more of:
(i) vascularization into said lumen of said device via the pores in said first nanoporous or microporous polymer layer or said second nanoporous or microporous polymer layer is observed;
(ii) a limited foreign body response to said device is observed; or
(iii) a limited ingress of cells, immunoglobulins, and cytokines into said lumen via said first and second nanoporous or microporous polymer layers, is observed.
2 . The method of claim 1 , further comprising releasing from said first nanoporous or microporous polymer layer or said second nanoporous or microporous polymer layer molecules secreted by said population of cells.
3 . The method of claim 1 , wherein said population of cells survives for at least one month after said transplanting.
4 . The method of claim 1 , wherein said population of cells comprises pancreatic islet cells and wherein said pancreatic islet cells respond to glucose levels of said subject by secreting insulin.
5 . The method of claim 1 , wherein said subject has or is predisposed to developing diabetes.
6 . The method of claim 1 , wherein said first and second nanoporous or microporous polymer layers are nanoporous polymer layers.
7 . The method of claim 1 , wherein said first and second nanoporous or microporous polymer layers are microporous polymer layers.
8 . The method of claim 1 , wherein said first nanoporous or microporous polymer layer is a nanoporous polymer layer and said second nanoporous or microporous polymer layer is a microporous polymer layer.
9 . The method of claim 1 , wherein said first and second nanoporous or microporous polymer layers comprise poly-caprolactone (PCL).
10 . The method of claim 1 , wherein said first and second nanoporous or microporous polymer layers are sealed along the entire periphery of said device thereby providing a closed lumen.
11 . The method of claim 1 , wherein said lumen comprises an opening at which said first and second nanoporous or microporous polymer layers are not sealed to each other.
12 . The method of claim 1 , wherein said lumen comprises an opening at which said first and second nanoporous or microporous polymer layers are not in contact with each other, said device further comprising a tubing comprising a first end and a second end distal to said first end, wherein said first end of said tubing is positioned in said opening and said second end of said tubing is configured to introduce said population of cells into said lumen.
13 . The method of claim 1 , wherein said lumen comprises a first opening and a second opening at which said first and second nanoporous or microporous polymer layers are not in contact with each other, said device further comprising a first tubing and a second tubing, each of said first and second tubing comprising a first end and a second end distal to said first end, wherein said first end of said first tubing is positioned in said first opening and said first end of said second tubing is positioned in said second opening, and wherein said second end of each tubing is used for ingress or egress of fluids from said lumen.
14 . The method of claim 13 , further comprising attaching said second ends of said first and second tubing to a fill port after said transplanting.
15 . The method of claim 14 , wherein said fill port comprises a first chamber in fluid communication at said fill port with said second end of said first tubing; and a second chamber in fluid communication at said fill port with said second end of said second tubing.
16 . A thin film device for transplanting cells into a subject in need thereof, said device comprising:
(a) a first nanoporous or microporous polymer layer;
(b) a second nanoporous or microporous polymer layer, wherein said first and second nanoporous or microporous polymer layers define a lumen between said first and second nanoporous or microporous polymer layers; and
(c) a therapeutically effective amount of a population of cells disposed in said lumen between said first and second nanoporous or microporous polymer layers,
wherein said first nanoporous or microporous polymer layer has a thickness of 10 μm to 100 μm and said second nanoporous or microporous polymer layer has a thickness of 10 μm to 100 μm, and wherein said device has a surface area of 1 cm 2 to 5 cm 2 , and wherein
(a) the pores in said first and second nanoporous or microporous polymer layers limit the ingress of cells, immunoglobulins, and cytokines into said lumen via said first and second nanoporous or microporous polymer layers,
(b) said pores are sized to promote vascularization into said lumen of said device,
(c) said device is configured to limit a foreign body response to said device after transplantation, and
(d) said pores are sized to release molecules secreted by said population of cells.
17 . The device of claim 16 , wherein the first and second polymer layers are nanoporous layers.
18 . The device of claim 16 , wherein said first and second nanoporous or microporous polymer layers are microporous layers.
19 . The device of claim 16 , wherein said first nanoporous or microporous polymer layer is a nanoporous polymer layer and said second nanoporous or microporous polymer layer is a microporous polymer layer.
20 . The device of claim 16 , wherein said first and second nanoporous or microporous polymer layers comprise poly-caprolactone (PCL).