Plasma microRNAs Are Potential Biomarkers of Acute Rejection After Hindlimb Transplantation in Rats.
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 (RT1l) 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.
Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Hiroki
H
Oda
Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Ryosuke
R
Ikeguchi
Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Hirofumi
H
Yurie
Department of Orthopaedic Surgery, Yawata Central Hospital, Yawatagotanda, Japan.
Yukitoshi
Y
Kaizawa
Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Souichi
S
Ohta
Research and Education Unit of Leaders for Integrated Medical System, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.
Koji
K
Yamamoto
Department of Physical Therapy, Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Tomoki
T
Aoyama
Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Shuichi
S
Matsuda