Plasma microRNAs Are Potential Biomarkers of Acute Rejection After Hindlimb Transplantation in Rats

Hiroki Oda; Ryosuke Ikeguchi; Hirofumi Yurie; Yukitoshi Kaizawa; Souichi Ohta; Koji Yamamoto; Tomoki Aoyama; Shuichi Matsuda

doi:10.1097/TXD.0000000000000620

Plasma microRNAs Are Potential Biomarkers of Acute Rejection After Hindlimb Transplantation in Rats

Transplant Direct. 2016 Oct 7;2(11):e108. doi: 10.1097/TXD.0000000000000620. eCollection 2016 Nov.

Authors

Hiroki Oda¹, Ryosuke Ikeguchi¹, Hirofumi Yurie¹, Yukitoshi Kaizawa², Souichi Ohta¹, Koji Yamamoto³, Tomoki Aoyama⁴, Shuichi Matsuda¹

Affiliations

¹ Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
² Department of Orthopaedic Surgery, Yawata Central Hospital, Yawatagotanda, Japan.
³ Research and Education Unit of Leaders for Integrated Medical System, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.
⁴ Department of Physical Therapy, Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Abstract

Background: The development of effective immunosuppressive regimens has resulted in many cases of successful hand transplantation. Visual skin inspection and histological evaluation are used to assess the rejection of hand transplants, but these methods are largely subjective. In this study, we aimed to determine the potential of microRNAs (miRNAs) as biomarkers for acute rejection in vascularized composite allotransplants.

Methods: In allograft group, 7 male Brown-Norway rats (RT1ⁿ) were used as donors and 13 male Lewis rats (RT1^l) were used as recipients. In control group, 8 Lewis rats were used as donors and recipients. The hindlimbs of donor rats were transplanted orthotopically to recipient rats. Skin changes were noted daily. Skin biopsies were obtained from 5 recipients and evaluated histologically. Plasma samples were obtained from the other 8 recipients before transplant and 7, 10, and 14 days posttransplant and used to measure miRNA expression.

Results: Skin changes occurred at a mean of 11.0 days posttransplant. Rejection in most skin biopsies taken 7 and 10 days posttransplant was histologically classified as grade 0, whereas that in most biopsies taken 14 days posttransplant was classified as grade 3. We found that expression of miRNA-146a and miRNA-155 was significantly upregulated at 10 and 14 days posttransplant compared with that at 7 days posttransplant. In control group, there were no significant changes in plasma miRNAs expressions.

Conclusions: The upregulation of plasma miRNA-146a and miRNA-155 was detected before the histological evaluation methods could diagnose complete rejection in the rat hindlimb transplantation model. Plasma miRNA-146a and miRNA-155 may be potential biomarkers of acute rejection after vascularized composite allotransplantation.