In recent years, breakthroughs in genetic engineering (GE) and cloning technology have led to the successful cultivation of “designated pathogen free (DPF) xenotransplantation (XENO) medical (M) pigs” (hereinafter referred to as GE-DPF-XENO-M pigs). Based on GE-DPF-XENO-M pigs, a large number of xenotransplantation experiments with non-human primates (NHPs) as recipients basically answered the most concerned questions: overcoming hyperacute rejection and cross species infection. These achievements directly accelerate to the emergence of a new “xenotransplantation subclinical research model”. At the end of 2021, Montgomery and Porrett teams in the United States successively transplanted GE pig kidney into the remains of 3 brain dead cases, no hyperacute rejection occurred after 48–72 hours. These three subclinical studies provide a scientific basis for xenotransplantation into clinical research. On January 7, 2022, Griffith, Maryland, USA, etc. transplanted a GE pig heart to a patient with severe heart failure and survived for 59 days. The above progress shows that xenotransplantation has taken a key step towards the stage of clinical research, which is worthy of our peers’ attention and reference.