Meeting of the beta cell minds
In 2016, experts in the field of stem cell-derived beta cell generation and transplantation met and discussed the most recent technology and research breakthroughs and their shared desire to further propel these studies towards clinical application. Let’s take a look at where some of these scientists are now.
Differentiation and characterization
Previously, Alireza Rezania had successfully differentiated embryonic stem cells and induced pluripotent stem cells into insulin-expressing cells resembling adult beta-cells. In February 2020, a patent application was published for Rezania’s methods to promote the differentiation of pluripotent stem cells, a continuation of his original work. Rezania has also applied for patents this year for his methodologies in genetically modifying universal donor cells and differentiating pancreatic endocrine cells to beta cells.
In 2016, Douglas Melton published a transcriptomic map of both the human and mouse pancreas and the cellular population structures of islets. Last year, Melton worked on a study with human stem cell differentiation, reporting transcriptional profiling of cells undergoing in vitro beta-cell differentiation. Two of his patents are also now currently active; one for methods to create stem cell-derived beta cells with a GSIS response in vitro and one for reprogramming endoderm cells to pancreatic beta-like cells.
Technology using the CRISPR-Cas9 system has become a game-changer in the scientific world, and has tremendous application potential for autoimmune disease treatments. It has been used in altering stem cells and reducing immunogenicity. Researchers have continued their work with CRISPR-Cas9 in the past few years:
- Luhan Yang was using CRISPR-Cas9 RNA-guided technology to edit porcine cells
- Chad Cowan was using CRISPR-Cas9 to create isogenic pairs of human stem cells and to alter stem cells
- 2020: filed for a patent for using CRISPR-Cas9 systems to target alleles, creating mutant cells to be used for therapeutic purposes
Qizhi Tang presented strategies to promote immune tolerance using autoimmune and alloimmune T cells and Tregs. More recently, she published reviews on using CAR-Tregs to promote immune tolerance with grafts and on adoptive cell therapy (ACT). She has also contributed to various papers, especially regarding Treg therapies for T1D and tumor growth suppression.
Alternative Transplant Sites and Platforms
Camillo Ricordi has worked on using the omentum as a potential site for stem cell-derived beta cells and has filed for two patents recently; one describing an apparatus to implant cells by applying negative pressure, and the other describing methods to implant therapeutic cells, creating a “biological scaffold.” Additionally, he has a patent for pancreatic cancer therapy which involves targeting cells and sending a therapeutic agent.
Mark Poznansky’s work deals with the use of chemorepellents (including chemokines) with microencapsulation to reduce the need for immunosuppression. Since 2016, his work has included treatment for cancer and for HPV-associated disease, both using a CXCL12 chemokine signaling inhibitor. He also has a patent filed for methods using antigen-presenting cells (APCs) in combination with anti-chemorepellents to treat disease.
Alice Tomei is developing a new microencapsulation technology using a conformal coating. This technology wraps islets with thin hydrogels, making them easier to transplant while protecting them from the immune system. Further research in 2019 was done studying islet viability and their glucose-stimulated insulin secretion, the patent for which was approved this year, offering a solution to immune rejection and autoimmune destruction.