# Composite porcine islet-kidney xenotransplants to cure diabetes and renal failure

> **NIH NIH U01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $1,258,779

## Abstract

Project Summary
This laboratory has previously developed a technique for transplanting pancreatic islets as part of a composite
islet-kidney (I-K), in which autologous islets are placed under the kidney capsule of the donor animal 6 to 8
weeks prior to transplantation. During this time, the islets become vascularized, so that there is no period of
ischemic damage to the islets when the I-K is subsequently transplanted to a recipient animal. There is also no
damage due to an immune response during this period, since the islets are autologous. We have demonstrated
the advantages of this technique over free islet transplantation for successful allogeneic islet transplantation,
both in miniature swine and in non-human primates. However, the applicability of this approach to clinical islet
transplantation is limited by the requirement for 6 to 8 weeks for vascularization, since this requirement limits the
approach to living donors. Extension of the approach to I-K xenotransplants could eliminate this limitation,
providing a cure for the currently unmet needs of many patients with end-stage diabetic nephropathy. Until
recently, however, the survival of xenograft kidneys was too short and the immunosuppression required too great
for the approach to be considered as a viable clinical option. Our recent studies now suggest that long-term
survival of porcine kidneys in baboons is possible using miniature swine donors and a tolerance-inducing
approach. The goal of this project is therefore to develop a clinically relevant tolerance induction strategy
for pig-to-baboon I-K transplantation. Specifically, we will: 1) Combine IK technology with our mixed
chimerism tolerance-inducing approach to determine whether tolerance of kidney extends to porcine islets and
reverses diabetes; 2) Combine IK plus VTL technologies to determine whether tolerance of kidney extends to
porcine islets and reverses diabetes; and 3) Compare and contrast mixed chimerism and VTL approaches with
regard to mechanism of tolerance to kidney and islets antigens. If successful, our approach could overcome the
current limitations to treatment of this clinically important entity by providing a virtually limitless donor supply of
islets and kidneys, a tolerance approach to avoid the need for long-term, chronic immunosuppression and a
donor kidney from inbred miniature swine, with intrinsic capacity to attain a size similar to that of human
recipients.

## Key facts

- **NIH application ID:** 10019062
- **Project number:** 1U01AI152881-01
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** DAVID H SACHS
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,258,779
- **Award type:** 1
- **Project period:** 2020-05-21 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10019062

## Citation

> US National Institutes of Health, RePORTER application 10019062, Composite porcine islet-kidney xenotransplants to cure diabetes and renal failure (1U01AI152881-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10019062. Licensed CC0.

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