Technology Description
An interdisciplinary team at Washington University in St. Louis has developed a multi-layered arteriovenous graft device that enhances the survival and function of stem cell transplants to treat Type 1 diabetes or other diseases. Artificial organs derived from stem cells could provide long-term, physiologically-regulated enzyme replacement treatment for a variety of conditions. In order to survive, these stem cells must have a sustainable and constant blood supply and they must be protected from attack by host immune system. This new vascular graft achieves those goals: the cells are directly connected to the blood supply to provide oxygen and nutrients for survival; and they are embedded in a hydrogel to protect them from the immune system. Furthermore, because the graft has direct proximity to arterial and venous blood, the transplanted cells can sense metabolites in the blood and secrete enzymes or growth factors in response to physiological conditions. Finally, the graft can be easily inserted, replaced or removed as needed to enhance the treatment or for patient safety.
This device could be used to deliver stem cell-derived insulin-secreting pancreatic beta-cells, which are able to treat Type 1 or Type 2 diabetes via real-time sensing of blood glucose and rapidly delivering intravenous insulin. The same method can also be adapted for thyroid or adrenal gland cells to deliver other cell types, enzymes or growth factors.
Stage of Research
The inventors have built a viable prototype graft that can be implanted with stem cell-derived beta-cell clusters. The inventors have also developed methods for reliable implantation and immune shielding of stem cell-derived beta-cell clusters. In vivo these cells are able sense blood glucose levels and rapidly secrete insulin in real-time. The inventors continue to currently develop and refine the next generation prototypes and implantation methods.
Applications
- Regenerative medicine device – graft to deliver biologically active, organ-specific differentiated stem cells, such as:
- beta-cells to secrete insulin and treat Type 1 and Type 2 diabetes by normalizing blood glucose
- Thyroid or adrenal gland cells for enzyme and growth factor-replacement therapy
Key Advantages
- Enhanced cell/artificial organ survival:
- Cells embedded in graft, surrounded by hydrogel to protect them from host immune system
- Cells have direct access to arterial blood supply to provide oxygen and nutrients
- Enhanced function/physiological regulation:
- For b-cells – cells in graft detect blood glucose fluctuations in real-time and can rapidly deliver insulin for glycemic control
- For other cells (e.g., thyroid or adrenal) – could detect needed levels of metabolites to secrete other enzymes or growth factors
- Easy access for removing or replacing – Graft can be implanted under a patient’s skin in an outpatient procedure and accessed percutaneously, allowing access to:
- Periodically load the graft with new cells
- Replace the device with a fresh graft
- Remove the device to ensure patient safety
- Convenient for patients – Cell therapy could provide a long-term glycemic control solution for patients with Type 1 and Type 2 diabetes without conventional blood monitoring and insulin injections
Patents
Website
Publications
Velazco-Cruz L, Song J, Maxwell KG, Goedegebuure MM, Augsornworawat P, Hogrebe NJ, Millman JR. Acquisition of Dynamic Function in Human Stem Cell-Derived β Cells.
Stem Cell Reports. 2019 Feb 12;12(2):351-365. doi: 10.1016/j.stemcr.2018.12.012. Epub 2019 Jan 17.
Millman JR, Pagliuca FW. Autologous Pluripotent Stem Cell-Derived β-Like Cells for Diabetes Cellular Therapy. Diabetes. 2017 May;66(5):1111-1120. doi: 10.2337/db16-1406. Review.
Song J, Millman JR. Economic 3D-printing approach for transplantation of human stem cell-derived β-like cells. Biofabrication. 2016 Dec 1;9(1):015002.
Millman JR, Xie C, Van Dervort A, Gürtler M, Pagliuca FW, Melton DA. Corrigendum: Generation of stem cell-derived β-cells from patients with type 1 diabetes. Nat Commun. 2016 Aug 4;7:12379. doi: 10.1038/ncomms12379. No abstract available.
Millman JR, Xie C, Van Dervort A, Gürtler M, Pagliuca FW, Melton DA. Generation of stem cell-derived β-cells from patients with type 1 diabetes. Nat Commun. 2016 May 10;7:11463. doi: 10.1038/ncomms11463. Erratum in: Nat Commun. 2016 Aug 04;7:12379.
Vegas AJ, Veiseh O, Gürtler M, Millman JR, Pagliuca FW, Bader AR, Doloff JC, Li J, Chen M, Olejnik K, Tam HH, Jhunjhunwala S, Langan E, Aresta-Dasilva S, Gandham S, McGarrigle JJ, Bochenek MA, Hollister-Lock J, Oberholzer J, Greiner DL, Weir GC, Melton DA, Langer R, Anderson DG. Corrigendum: Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice. Nat Med. 2016 Apr;22(4):446. doi: 10.1038/nm0416-446e. No abstract available.
Vegas AJ, Veiseh O, Gürtler M, Millman JR, Pagliuca FW, Bader AR, Doloff JC, Li J, Chen M, Olejnik K, Tam HH, Jhunjhunwala S, Langan E, Aresta-Dasilva S, Gandham S, McGarrigle JJ, Bochenek MA, Hollister-Lock J, Oberholzer J, Greiner DL, Weir GC, Melton DA, Langer R, Anderson DG. Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice. Nat Med. 2016 Mar;22(3):306-11. doi: 10.1038/nm.4030. Epub 2016 Jan 25. Erratum in: Nat Med. 2016 Apr;22(4):446.
Pagliuca FW, Millman JR, Gürtler M, Segel M, Van Dervort A, Ryu JH, Peterson QP, Greiner D, Melton DA. Generation of functional human pancreatic β cells in vitro. Cell. 2014 Oct 9;159(2):428-39. doi: 10.1016/j.cell.2014.09.040.
