Genome editing for engineering stem cell-derived pancreatic β cells: recent trends and future perspectives

Abstract

Although engineering transplantable tissues for clinical applications is difficult, cryopreserving those tissues to create pre-made engineered tissue for emergency transplantation is an even greater challenge. It remains uncertain whether the cryopreservation of engineered tissues will become a reality, but if so, it could have a significant impact on public health by saving lives and simplifying clinical treatment procedures. All in all, the potential implications of this innovation could have far-reaching consequences for the medical field as a whole. This review introduces the basic principles of cryopreservation techniques, including the procedures and components involved. Additionally, a list of its applications to engineered tissue is presented.

Establishment and Advancement of Pancreatic Organoids

“…Ascites or pleural fluid has also been used as a source to generate PDOs [53]. Pancreatic organoids can contribute considerably to the growing demand for translational research and their usage has expanded synergistically with multiomics, genome editing [54,55], microfluidic chips [56], bioprinting [57], and artificial intelligence [58].…”

Developments in endoderm and pancreatic β-cell differentiation from human pluripotent stem cells

“…Recent advances in genome editing technology have made it possible to introduce any genetic factor into the genome. This capability enables the modification of cells to incorporate functional genes, which can be further refined to either evade post-transplant immunity or enhance survival during the post-transplant angiogenesis period [16,18,68]. To functionally improve hPSC-derived β-cells and facilitate their purification, genes such as PDX1, INS promoter, SLC30A8, and ZNF148 can be targeted for editing.…”

“…To reduce the risk of allograft rejection by the recipient's immune system, modifications can be made to B2M, CIITA, CD47, HLA, PD-L1, and CXCL10. Additionally, editing RNLS may offer protection against ER stress [18,68].…”

“…As technologies for differentiating high-functioning stem cells and developing biomaterials suitable for in vivo transplantation rapidly advance, genome editing tools, particularly those based on the CRISPR/ Cas9 system, show promise. These tools can permanently modify the genome sequence, thereby altering the phenotype of cell O therapeutics [17,18]. This review explores the essential growth factors and small molecules involved in the differentiation of hPSCs into pancreatic β cells, as well as how this differentiation process can be applied to treat type 1 diabetes.…”