Blocking "Xenophagocytosis": A Key Step Toward Growing Human Organs in Animals
Release time:
2026-06-12
Organ shortage is a long-standing challenge in global transplant medicine. Patients who undergo allogeneic or xenogeneic organ transplantation often require lifelong immunosuppression, which limits their quality of life and long-term prognosis. More than a decade ago, scientists proposed the concept of interspecific blastocyst complementation (IBC): injecting pluripotent stem cells from one species into the blastocyst of another species, allowing donor cells to develop into functional organs within the host. Theoretically, this could enable the growth of human organs in large animals such as pigs. However, in practice, the chimeric efficiency of cross-species cells has been extremely low, long regarded as an "insurmountable barrier."
Recently, a research team led by Professor Hiromitsu Nakauchi at Stanford University School of Medicine published a breakthrough study in Cell, revealing for the first time the core mechanism behind this obstacle—"xenophagocytosis"—and proposing actionable strategies to block it, offering a new path toward efficient generation of human organs in animals.
The team found that in mouse-rat interspecific chimeric embryos, the number of donor cells dropped sharply between days 9 and 11 of development. Further tracking showed that primitive macrophages, the earliest innate immune cells to appear, selectively recognize and engulf living cross-species cells but not same-species cells. This clearance mechanism was named "xenophagocytosis."
At the molecular level, the surface of cross-species cells exhibits significantly elevated levels of phosphatidylserine, an "eat-me" signal recognized by the macrophage receptor Axl. Meanwhile, the "don't-eat-me" signal CD47, which protects cells from phagocytosis, is underexpressed in cross-species cells, leading to a signaling imbalance.
Targeting this mechanism, the team proposed and validated three independent strategies:
Host-side intervention: Depleting macrophages or knocking out the Axl receptor in mouse embryos.
Donor-side intervention: Overexpressing the "don't-eat-me" signal CD47 in human or pluripotent stem cells.
Donor-side intervention: Overexpressing ATP11C flippase, which regulates phosphatidylserine distribution, to reduce exposure of the "eat-me" signal.
Experiments showed that any of these strategies significantly blocked xenophagocytosis, greatly increased the chimeric rate of rat cells in mouse embryos, and enabled more efficient reconstruction of rat pancreata. More importantly, in human-cell–mouse-embryo models, depleting host macrophages similarly enhanced the chimeric ability of human donor cells.
This study not only explains why interspecific chimerism has been difficult to achieve but also provides directly actionable solutions. Combined with the team's earlier concept of the "organ niche"—reserving developmental space for a missing organ in the host—blocking xenophagocytosis could bring the goal of "growing human organs in pigs" from theory to reality. If such organs can be successfully generated in the future, they could fundamentally solve the problem of immune rejection, making organ transplantation no longer dependent on donations or lifelong medication.
Experts in the field believe that this study has found the key to protecting cross-species cells from early immune system clearance, opening a new door for regenerative medicine.
Latest developments
Yinfeng Foundation Honored as "2025 Public Welfare Donor" by Jinan Red Cross
Looking ahead, Yinfeng Foundation will use this recognition as an opportunity to further deepen its strategic collaboration with the Jinan Red Cross, expand cooperation in areas such as life health and emergency response, and continue to empower efforts to accelerate the construction of a "new, strong, excellent, rich, beautiful, and high-quality" modern socialist strong capital city, contributing even more Yinfeng strength to this endeavor.
The team successfully developed the CryoSIM platform, an intelligent microfluidics and deep learning-integrated system. This platform deeply integrates core technologies of deep learning and microfluidics to enable high-throughput, high-precision automated analysis of oocyte membrane permeability. It provides a novel technological tool for optimizing and advancing the clinical translation of oocyte cryopreservation techniques. Additionally, it offers an innovative practical paradigm for the application of artificial intelligence in low-temperature biomedicine and reproductive medicine.
Public Welfare Partnership: A Special Letter from the Jinan Red Cross
On the afternoon of January 30, 2026, the Jinan Red Cross presented a letter of special significance to the Shandong Yinfeng Life Science Public Welfare Foundation (hereinafter referred to as the Yinfeng Foundation).
World’s First Achievement Highlights Brand Leadership
In the future, Yinfeng Life Science Research Institute will continue to uphold its mission of "Dedicated to Medical Technology, Safeguarding Human Health." It will empower brand building with more original and pioneering scientific and technological achievements, contributing wisdom and strength to Shandong's goal of building a national regional innovation hub and promoting Chinese brands on the global stage.
Global First Ovarian Tissue Dual Activation Technology Debuts at 2025 Jinan Achievements Conference
Currently, the ovarian tissue dual activation technology has been successfully applied in clinical practice at Beijing University of Chinese Medicine Shenzhen (Longgang) Hospital, having treated over 400 patients with a treatment success rate of 70%. Over the next three years, Shandong Yinfeng Life Science Research Institute plans to use Jinan as a center to gradually expand the transformation and application of this technological achievement nationwide.
According to the latest announcement from the International Society of Cryobiology, Professor Xu Yi from the School of Health Science and Engineering at the University of Shanghai for Science and Technology, and a member of the Yinfeng Cryomedicine Expert Committee, has been elected as a Board Governor of the Society for a three-year term (2026–2028). The election was conducted through a democratic vote by all members worldwide, with three new Board Governors elected. Professor Xu Yi is the only scholar from Asia elected to the Society’s Board of Governors this time and the third elected scholar from mainland China in the Society’s 60-year history.
Yinfeng Life Continuation Plan
Address: Yinfeng Biotechnology Park, 1758 Gangyuan 6th Road, High-tech Zone, Jinan City, Shandong Province
Zip Code: 250102
Telephone: 0086-0531-88897351
Mobile: 0086-19953155515
Mobile website
Official WeChat Public Number
Links:Red Cross Society of China丨Shandong Red Cross Society丨Shandong Provincial Health Commission | Yinfeng Group| Yinfeng Biological Group
All rights reserved©Yinfeng Life Continuation Powered by www.300.cn SEO
