Ultrasonic histotripsy for cell therapy

Liver transplantation is the mainstay of the treatment for end stage liver diseases including metabolic and congenital liver diseases. The number of suitable donor organs is however limited and a whole-liver transplant requires complex surgery. Cell therapy, such as intraportal hepatocytes transplantation, has been considered as a bridging alternative therapy to liver transplantation but has shown a mixed clinical outcome with limited success. One of its main limitations is the low level of engraftment of transplanted hepatocytes due to the innate immune reaction, blood-mediated inflammatory reaction and the liver to body weight ratio of the patient, which makes it difficult to achieve extensive proliferation of the transplanted cells.

Research Aim

The main aim of this study is to demonstrate an alternative to the traditional intraportal cell therapy and that is a novel approach mediated by High-Intensity Focused Ultrasound (HIFU). The proposed method creates a cavity inside the liver through histotripsy (mechanical tissue fractionation) followed by the direct injection of donor hepatocytes into the cavity. This project is in collaboration with the Institute for Liver and Digestive Health, and Hepato-pancreatic-biliary and Liver Transplantation Surgery, Royal Free Hospital, University College London.

A schematic diagram of the in vivo experimental set up is shown in Fig. 1(A). Figure 1(B) shows the proliferating transplanted hepatocytes inside the cavity detected by the Ki-67 staining.

Figure 1(A) Illustrating the in vivo HIFU experimental set up; (B) Proliferating cells stained by Ki-67 inside the cavity. Arrows show strongly positive bi-nucleated cells. Magnification x100.

Ki Joo Pahk