Intramuscular Transplantation of Human Pluripotent Stem Cell-derived Pancreatic Endocrine Cells in Mice

Human pluripotent stem cell (hPSC)-derived pancreatic endocrine cells constitute a promising source for diabetes cell therapy and disease modeling. Although several differentiation protocols have been established, in vivo implantation is commonly required to study maturation and function within a physiological context. Most transplantation approaches rely on sites such as the kidney capsule or subcutaneous space, which may pose technical or physiological limitations. Here, we present a detailed protocol for the intramuscular transplantation of hPSC-derived pancreatic SC-islets into immunodeficient mice. This site allows for straightforward surgical access, reduced invasiveness, and reliable graft retrieval for subsequent analysis. The procedure enables intramuscular implantation of stem cell-derived islets and supports their recovery for downstream assessment of insulin secretion following an oral glucose challenge. The protocol includes steps for cluster preparation and compaction, transplantation surgery, in vivo glucose-stimulated insulin secretion (GSIS), and graft retrieval for histological analysis, providing a reproducible framework for intramuscular transplantation in preclinical mouse models.