Xenotransplantation - Overview of Pig Kidney Transplantation Development in the United States

2025-06-19

Due to a large number of patients awaiting kidney transplantation in the U.S. (over 90,000 people), the long-standing issue of organ shortage remains unresolved. Scientists have turned their attention to xenotransplantation—particularly transplanting genetically modified pig kidneys into humans—as a potential solution to bridge the gap in organ supply.

I. Key Developments and Milestones

✅ 1. Breakthrough Experiment at NYU Langone Health (2021)

A genetically modified pig kidney was transplanted into a brain-dead patient for the first time.
Successfully monitored for two days with no signs of rejection.
The donor pig lacked the alpha-gal sugar molecule, which typically triggers a strong immune response in humans.
The kidney demonstrated urine production and other metabolic functions.

✅ 2. UAB (University of Alabama at Birmingham) Study (2022)

Successfully transplanted two genetically modified pig kidneys into a brain-dead patient.
The grafts functioned normally for over 74 hours without immediate rejection.

✅ 3. Second Successful Transplant at NYU (2023)

Maintained pig kidney function in a brain-dead patient for 74 days.
One of the longest recorded durations for a pig kidney transplant.

✅ 4. Landmark Living Human Transplant at University of Maryland Medical Center (2024)

First-ever pig kidney transplant into a living human patient.
The recipient was a patient with end-stage kidney disease, ineligible for a human kidney transplant.
The pig kidney underwent 10 genetic modifications, including those to reduce rejection and suppress porcine endogenous retrovirus (PERV).
Kidney function was maintained for over a month without severe rejection.

II. Scientific and Technological Breakthroughs

🧬 Gene Editing Technologies

CRISPR and TALENs are used to eliminate pig genes responsible for immune rejection.
Human anti-rejection genes (e.g., CD46, EPCR) are inserted into the pig genome.

🦠 PERV (Porcine Endogenous Retrovirus)

Once considered a major risk in pig-to-human transplantation, now significantly reduced through gene editing.

🧪 Immunosuppressive Strategies

Novel combinations of immunosuppressants, such as anti-CD40 antibodies, are used to prevent acute rejection.

III. Challenges and Ethical Controversies

Long-term rejection Medium- to long-term survival of pig kidneys in humans remains unproven.
Risk of porcine viruses Despite modifications, long-term cross-species viral risks require monitoring.
Animal ethics Genetic engineering and mass breeding of pigs raise ethical concerns.
Medical equity If commercialized, the treatment may lead to disparities in access.

IV. Future Outlook

Additional living human clinical trials are expected between 2025–2026.
If long-term success is achieved, pig kidney transplants may serve as:
- A temporary kidney source for end-stage renal disease patients
- An alternative treatment for patients with no human donor match

Long-Term Goal: To establish a reliable xenogeneic organ supply chain and solve the global organ shortage crisis.

一、背景與動機

由於美國等待腎臟移植的患者人數龐大（超過90,000人），器官短缺問題長期未解。科學家開始將目光轉向異種移植，特別是將基因改造豬的腎臟移植至人類，以補足器官來源。

二、重要進展與里程碑

✅ 1. 2021年 NYU Langone Health 的突破性實驗

將一顆基因改造豬腎臟移植到腦死病人體內，首次成功連續觀察兩天，沒有排斥反應。
使用了去除 alpha-gal 糖分子的基因改造豬（人類會對 alpha-gal 產生強烈免疫反應）。
腎臟能夠製造尿液與其他代謝功能。

✅ 2. 2022年 UAB（阿拉巴馬大學）實驗

成功將兩顆基因改造豬腎移植至腦死病人。
經過超過74小時觀察，移植物發揮正常功能，無立即性排斥。

✅ 3. 2023年 NYU 再次移植成功（74天）

腦死病人身上維持豬腎功能長達74天。
此為迄今持續時間最長的豬腎移植試驗之一。

✅ 4. 2024年馬里蘭大學醫學中心的重大突破

試驗性地將豬腎首次移植到活人身上。
移植對象是一名末期腎病、無法接受人類腎臟的病患。
豬腎臟使用了10項基因改造，包括抗排斥與控制豬病毒活性（PERV）。
成功維持腎功能超過1個月，未發生嚴重排斥。

三、科學與技術關鍵

🧬 基因編輯技術

使用 CRISPR 或 TALENs 技術刪除導致免疫排斥的豬基因。
加入人類的抗排斥相關基因，如 CD46、EPCR 等。

🦠 PERV（豬內源性逆轉錄病毒）問題

曾被認為是豬器官移植的重大風險，但透過基因編輯已大幅降低風險。

🧪 免疫抑制策略

搭配新的免疫抑制藥物組合（如 anti-CD40抗體）來預防急性排斥反應。

四、挑戰與倫理爭議

長期排斥反應豬腎在人體內的中長期存活率仍待驗證。
豬源病毒感染風險雖已改造，但仍需長期監測潛在跨物種病毒。
動物權與倫理爭議豬的基因編輯與大量飼養涉及道德討論。
醫療公平性若成為商業化醫療，可能產生分配不均問題。

五、未來展望

預計2025～2026年，可能會進行更多活人臨床試驗。
若長期成功，未來豬腎移植可能成為：
- 末期腎病人的「過渡性腎源」。
- 特殊病患的替代治療方式。
長期目標：建立穩定的異種器官供應鏈，解決全球器官短缺問題。