Xenotransplanted Heart with Increased Survivability
Written by Rency Dhaduk
Edited by Emily Moran
March 21, 2022
Edited by Emily Moran
March 21, 2022
For patients who are unable to get heart transplantation in time before heart failure, genetically modified pig hearts are the new source of transplant for end-stage failure. Xenograft transplant is when organs or tissues are transplanted among two different species, such as from animals to humans. Usually, there is heart failure within 1 month of the xenograft transplantation due to excessive growth and heart pressure differences leading to the patient’s death. However, administering cancer medication and reducing agents regularly can increase the living time by 6 months. At the University of Maryland, researchers are studying how to reduce that overgrowth by studying the dynamics of growth hormone receptor knockout (GHR KO) xenografts to increase the survival time of baboon recipients and eventually human patients.
For the model, the pig donors were divided into two groups based on the presence and absence of GHR KO. Researchers transplanted pig hearts into baboon recipients weighing 5-30 kgs. The cardiovascular system works differently in pigs and baboons. Due to this mismatch, excessive heart growth is observed after transplantation leading to heart failure (Goerlich, 2021). The growth hormone receptor works to regulate growth mechanisms. GHR knockout pigs have smaller organs and deficient growth hormones. These knocked-out pigs have been proposed to be the solution to internal growth in grafts as deactivated GHR is likely to reduce the overgrowth (Goerlich, 2021).
The grafts with GHR showed more overgrowth and heartbeat relaxation differences after the transplant. Grafts without GHR KO showed more of the typical complications like increased wall thickness, decreased wall dimensions, respiratory distress, elevated liver enzymes, and decreased survivability (Goerlich, 2021). Baboons that were given a GHO KO graft had a survival rate of more than 6 months. This tissue showed normal heart pressure and functions, minimal wall thickness, asymptomatic for diastolic heart failure, and passage of fluid through the circulatory system was normal. It is nonessential to match physiologic factors for life-limiting xenograft growth. Even with a mismatch, GHR KO overgrowth was much reduced. Grafts with GHR showed excess postoperative growth and fewer chances of survival (Goerlich, 2021). GHR KO had much higher survival chances. The important finding from the study is that if an overgrowth is controlled in baboons, it will be relevant to humans too.
References
Goerlich, C. E., Griffith, B., Hanna, P., Hong, S. N., Ayares, D., Singh, A. K., & Mohiuddin, M. M. (2023). The growth of xenotransplanted hearts can be reduced with growth hormone receptor knockout pig donors. The Journal of thoracic and cardiovascular surgery, 165(2), e69–e81. https://doi.org/10.1016/j.jtcvs.2021.07.051
Image Source: “Doctor Xray skeleton” by Mohamed Hassan licensed under CC0