A retrievable implant for the long-term encapsulation and survival of therapeutic xenogeneic cells.
Suman BoseLisa R VolpattiDevina ThionoVolkan YesilyurtCollin McGladriganYaoyu TangAmanda L FacklamAmy WangSiddharth JhunjhunwalaOmid VeisehJennifer Hollister-LockChandrabali BhattacharyaGordon C WeirDale L GreinerRobert S LangerDaniel G AndersonPublished in: Nature biomedical engineering (2020)
The long-term function of transplanted therapeutic cells typically requires systemic immune suppression. Here, we show that a retrievable implant comprising a silicone reservoir and a porous polymeric membrane protects human cells encapsulated in it after implant transplantation in the intraperitoneal space of immunocompetent mice. Membranes with pores 1 µm in diameter allowed host macrophages to migrate into the device without the loss of transplanted cells, whereas membranes with pore sizes <0.8 µm prevented their infiltration by immune cells. A synthetic polymer coating prevented fibrosis and was necessary for the long-term function of the device. For >130 days, the device supported human cells engineered to secrete erythropoietin in immunocompetent mice, as well as transgenic human cells carrying an inducible gene circuit for the on-demand secretion of erythropoietin. Pancreatic islets from rats encapsulated in the device and implanted in diabetic mice restored normoglycaemia in the mice for over 75 days. The biocompatible device provides a retrievable solution for the transplantation of engineered cells in the absence of immunosuppression.
Keyphrases
- induced apoptosis
- cell cycle arrest
- endoplasmic reticulum stress
- signaling pathway
- gene expression
- oxidative stress
- inferior vena cava
- drug delivery
- adipose tissue
- type diabetes
- high fat diet induced
- metabolic syndrome
- soft tissue
- skeletal muscle
- cell therapy
- cell proliferation
- transcription factor
- insulin resistance
- pulmonary embolism
- optical coherence tomography
- metal organic framework
- cancer therapy