Establishment and evaluation of a modified mouse model of renal subcapsular transplantation of microvolume cells

The renal subcapsular space provides an easily accessible, nutrition-rich pocket that supports engraftment, and as such, is often used as a site for stem and cancer cell transplantation. Renal capsule transplantation requires high technical requirements, the recipient mice have greater surgical damage, the mouse kidney is small and the kidney capsule is fragile, and the operation is easy to fail. The conventional method is not suitable for microvolume cell transplantation to this site in animals with a small kidney, such as mice, due to high risks of cell loss or dislocation or injury to the capsule. In this study, we developed and validated a modified approach for the mouse model of renal subcapsular transplantation of microvolume mouse skeletal stem cells (SSCs). We used a pipette with a refined tip to separate the capsule from the parenchyma. Moreover, we used cells suspended in Matrigel rather than a liquid carrier for transplantation. Using the modified method, we were able to transplant microvolume mouse SSCs as low as 0.2 μL beneath the mouse renal capsule with excellent reproducibility. After 4 weeks of in vivo culture, the implanted mouse SSCs formed grafts on the surface of the parenchyma at the target site of transplantation. Histological staining of the grafts indicated osteogenic, fibrogenic, and lipogenic differentiation. Micro-CT imaging of the grafts revealed bone formation. This modified model could be used to effectively transplant different types of microvolume cells to the renal subcapsular space when the donor cells are difficult to acquire or the recipient mice have a very small size kidney.