Biomarkers from subcutaneous engineered tissues predict acute rejection of organ allografts

Author:

Urie Russell R.1ORCID,Morris Aaron1ORCID,Farris Diana2,Hughes Elizabeth1ORCID,Xiao Chengchuan3ORCID,Chen Judy24ORCID,Lombard Elizabeth1ORCID,Feng Jiane5,Li Jun Z.67ORCID,Goldstein Daniel R.248ORCID,Shea Lonnie D.19ORCID

Affiliation:

1. Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.

2. Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.

3. Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.

4. Program in Immunology, University of Michigan, Ann Arbor, MI 48109, USA.

5. Animal Phenotyping Core, University of Michigan, Ann Arbor, MI 48109, USA.

6. Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.

7. Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.

8. Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, USA.

9. Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.

Abstract

Invasive graft biopsies assess the efficacy of immunosuppression through lagging indicators of transplant rejection. We report on a microporous scaffold implant as a minimally invasive immunological niche to assay rejection before graft injury. Adoptive transfer of T cells into Rag2 −/− mice with mismatched allografts induced acute cellular allograft rejection (ACAR), with subsequent validation in wild-type animals. Following murine heart or skin transplantation, scaffold implants accumulate predominantly innate immune cells. The scaffold enables frequent biopsy, and gene expression analyses identified biomarkers of ACAR before clinical signs of graft injury. This gene signature distinguishes ACAR and immunodeficient respiratory infection before injury onset, indicating the specificity of the biomarkers to differentiate ACAR from other inflammatory insult. Overall, this implantable scaffold enables remote evaluation of the early risk of rejection, which could potentially be used to reduce the frequency of routine graft biopsy, reduce toxicities by personalizing immunosuppression, and prolong transplant life.

Publisher

American Association for the Advancement of Science (AAAS)

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