Advancements in Fetal Organ Transplantation: A Leap Towards Xenotransplantation

News Mania desk/Agnibeena Ghosh/1st May 2024

In a pioneering feat of medical science, surgeons in Japan have achieved a groundbreaking milestone by successfully transplanting kidney tissue from one rat fetus to another while the recipient was still in its mother’s womb. Spearheaded by study lead Takashi Yokoo, a nephrologist at Jikei University School of Medicine in Tokyo, this surgical endeavor marks the initial phase towards ultimately transplanting fetal pig kidneys into human fetuses that fail to develop functioning kidneys.

Yokoo affirms, “Our project is the first of its kind,” distinguishing it from prior endeavors where researchers injected cells and amniotic fluid into fetuses, including humans. These transplants constitute the premier reports of organ and tissue transplants conducted in utero.

The concept of transplanting organs before birth holds immense promise as it allows the organ to mature and evolve alongside the fetus, potentially ensuring its functionality at birth and diminishing the risk of rejection. Glenn Gardener, a fetal surgeon at Mater Mothers’ Hospital in Brisbane, Australia, lauds the achievement, labeling it as “lovely data.”

The modus operandi of Yokoo and his colleagues entailed genetically modifying rats to express a green fluorescent protein in their kidneys, facilitating the tracking of the transplanted tissue. Subsequently, they extracted the green kidney tissue from rat fetuses and delicately inserted it under the skin in the backs of 18-day-old rat fetuses developing within their mothers’ wombs. Following the customary gestation period of approximately 22 days, the rat pups were born.

Over time, the transplanted tissue gradually matured, forming waste-filtering units termed glomeruli, alongside well-defined inner and outer kidney structures. Within two-and-a-half weeks, the kidneys commenced urine production, mirroring the typical developmental trajectory. However, owing to the absence of a connection to the ureter, the urine had no outlet, prompting researchers to continuously drain the kidney until the rats were euthanized around five months later.

Out of the nine fetuses subjected to surgical transplantation in four pregnant rats, eight manifested fluorescent-green kidneys, signifying a high success rate. Upon meticulous examination, it was discerned that the fetuses’ blood vessels had permeated the donated tissue, thereby mitigating the likelihood of rejection by the immune system—a notable breakthrough in organ transplantation dynamics.

The findings of the rat study, unveiled on the bioRxiv preprint server on April 20, underscore Yokoo’s overarching objective of transplanting fetal pig kidneys into human fetuses afflicted with Potter syndrome. Yokoo embarked on another experimental trajectory by transplanting mouse kidney tissue into rat fetuses to assess xenotransplantation feasibility. The intervention proved efficacious in four rats, with the kidneys exhibiting ten days of uninterrupted development before encountering signs of rejection by day 18, which could be alleviated through immunosuppressant administration.

Yokoo postulates that fetal tissue’s diminished propensity to elicit an immune response renders genetic modification dispensable prior to transplantation, unlike adult tissue. Yokoo’s foray into pig-to-pig fetal transplants and subsequent pig-to-monkey fetal transplants attests to his multifaceted research endeavors aimed at broadening the horizons of xenotransplantation.

While hailed as a seminal breakthrough, Yokoo’s rat experiments are perceived as a crucial initial stride towards xenotransplantation’s realization in humans, as elucidated by Maria Yasuoka, a medical anthropologist at Otaru University of Commerce in Hokkaido, Japan. However, other experts exercise caution, emphasizing the need for further research and regulatory approvals before clinical translation.

In essence, Yokoo’s audacious venture heralds a new era in organ transplantation, underpinned by relentless innovation and unwavering commitment to surmounting biomedical frontiers.