An intrinsic link to an extrinsic cause of cardiac xenograft growth after xenotransplantation: Commentary (in response to): Zaman, R. et al. Selective loss of resident macrophage‐derived insulin‐like growth factor‐1 abolishes adaptive cardiac growth to stress. Immunity 54, 2057–2071.e6 (2021). (10th January 2022)

• Record Type: Journal Article
• Authors: Goerlich, Corbin E.; Singh, Avneesh; Treffalls, John A.; Griffith, Bartley; Ayares, David; Mohiuddin, Muhammad M.
• Is Part Of: Xenotransplantation. Volume 29:Number 1(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-01-10
• Subjects: Xenografts -- Periodicals; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/xen.12724
• Languages: English
• ISSNs: 0908-665X

Abstract

Abstract: Post‐transplantation cardiac xenograft growth in an orthotopic pig to baboon model is a life‐limiting phenomenon that is poorly understood. Possible causes of growth include both intrinsic and extrinsic etiologies. Extrinsic causes are thought to be attributed to maladaptive hypertrophy as a result of increased mean arterial pressure experienced by the cardiac xenograft after transplantation. Intrinsic causes are thought to be a result of discordant growth between pig xenografts and recipients. This results in intrinsic xenograft growth that parallels the donor and continues in a recipient in which growth is relatively minimal, controlled in part by the growth hormone receptor, IGF‐1 axis. Recently, Zaman, et al. published a study titled, "Selective loss of resident macrophage‐derived insulin‐like growth factor‐1 abolishes adaptive cardiac growth to stress, " in Immunity, Volume 54; Issue 9, pp. 2057–2071. They demonstrated that insulin growth factor‐secreting resident macrophages that sense hypertensive stress are a mechanistic link to hypertension and maladaptive hypertrophy in the setting of hypertension. While notable in its own right, we comment on how this work may shed light on a new underlying mechanism for the use of growth hormone receptor knockout (GHRKO) pig donors and its role in addressing post‐transplantation xenograft growth. We hypothesize that GHRKO pig donors contain syngeneic resident cardiac macrophages that abrogate IGF‐1 mediated maladaptive hypertrophy from hypertension. Futures studies in post‐transplantation cardiac xenotransplantation growth should examine this mechanism as a potential contributor.