Donor and Recipient Adipose-Derived Mesenchymal Stem Cell Therapy for Rat Lung Transplantation.


Journal

Transplantation proceedings
ISSN: 1873-2623
Titre abrégé: Transplant Proc
Pays: United States
ID NLM: 0243532

Informations de publication

Date de publication:
Sep 2022
Historique:
received: 17 01 2022
revised: 03 05 2022
accepted: 22 05 2022
pubmed: 31 8 2022
medline: 9 11 2022
entrez: 30 8 2022
Statut: ppublish

Résumé

Mesenchymal stem cells (MSCs) are beginning to be proven as immunosuppressant in the field of organ transplantation. However, the effects of MSC origin (donor or recipient) on immunosuppression are not clear. Hence, we investigated the effects of recipient and donor adipose-derived MSCs (ADMSCs) on immunosuppression in a rat lung transplantation model. Subjects were divided into no treatment, tacrolimus administration, recipient ADMSC administration, donor ADMSC administration, and mixed donor and recipient ADMSC administration groups. ADMSC-administered groups were also treated with tacrolimus. Histologic study, immunofluorescence, immunohistochemistry, enzyme-linked immunosorbent assay, and polymerase chain reaction were used for various analyses. Fluorescently labeled ADMSCs were predominant in the grafted donor lung, but not in the recipient lung, on day 5. On day 7, the pathologic rejection grades of the grafted donor lung were significantly lower in the ADMSC-administered groups (P < .05) and did not differ among these groups. Although serum hepatocyte growth factor and vascular endothelial growth factor levels did not differ among the groups, interleukin 10 level was slightly higher in the ADMSC-administered groups. The numbers of infiltrating regulatory T cells in the grafted lung were significantly higher in the ADMSC-administered groups (P < .05) but did not differ with cell origin. Transcriptional analysis suggested interleukin 6 suppression to be the main overlapping immunosuppressive mechanism, regardless of origin. Therefore, a donor or recipient origin may not influence the immunosuppressive efficacy of ADMSCs in our rat lung transplantation model. Collectively, the results indicate that allogenic ADMSCs, regardless of their origin, may exert similar immunosuppressive effects in clinical organ transplantation.

Sections du résumé

BACKGROUND BACKGROUND
Mesenchymal stem cells (MSCs) are beginning to be proven as immunosuppressant in the field of organ transplantation. However, the effects of MSC origin (donor or recipient) on immunosuppression are not clear. Hence, we investigated the effects of recipient and donor adipose-derived MSCs (ADMSCs) on immunosuppression in a rat lung transplantation model.
METHODS METHODS
Subjects were divided into no treatment, tacrolimus administration, recipient ADMSC administration, donor ADMSC administration, and mixed donor and recipient ADMSC administration groups. ADMSC-administered groups were also treated with tacrolimus. Histologic study, immunofluorescence, immunohistochemistry, enzyme-linked immunosorbent assay, and polymerase chain reaction were used for various analyses.
RESULTS RESULTS
Fluorescently labeled ADMSCs were predominant in the grafted donor lung, but not in the recipient lung, on day 5. On day 7, the pathologic rejection grades of the grafted donor lung were significantly lower in the ADMSC-administered groups (P < .05) and did not differ among these groups. Although serum hepatocyte growth factor and vascular endothelial growth factor levels did not differ among the groups, interleukin 10 level was slightly higher in the ADMSC-administered groups. The numbers of infiltrating regulatory T cells in the grafted lung were significantly higher in the ADMSC-administered groups (P < .05) but did not differ with cell origin. Transcriptional analysis suggested interleukin 6 suppression to be the main overlapping immunosuppressive mechanism, regardless of origin. Therefore, a donor or recipient origin may not influence the immunosuppressive efficacy of ADMSCs in our rat lung transplantation model.
CONCLUSIONS CONCLUSIONS
Collectively, the results indicate that allogenic ADMSCs, regardless of their origin, may exert similar immunosuppressive effects in clinical organ transplantation.

Identifiants

pubmed: 36041932
pii: S0041-1345(22)00431-6
doi: 10.1016/j.transproceed.2022.05.038
pii:
doi:

Substances chimiques

Tacrolimus WM0HAQ4WNM
Vascular Endothelial Growth Factor A 0
Immunosuppressive Agents 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1998-2007

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Koichiro Shimoyama (K)

Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Medical-Engineering Hybrid Professional Development Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Tomoshi Tsuchiya (T)

Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Division of Nucleic Acid Drug Development, Research Institute for Science and Technology, Tokyo University of Science, Chiba, Japan. Electronic address: tsuchiya@med.u-toyama.ac.jp.

Hironosuke Watanabe (H)

Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Abdelmotagaly Ergalad (A)

Center for Preclinical Surgical and Interventional Research, Texas Heart Institute, Houston, Texas.

Mayumi Iwatake (M)

Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Takuro Miyazaki (T)

Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Yasumasa Hashimoto (Y)

Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Medical-Engineering Hybrid Professional Development Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Yu-I Hsu (YI)

Department of Biomedical Engineering, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.

Go Hatachi (G)

Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Keitaro Matsumoto (K)

Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Medical-Engineering Hybrid Professional Development Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Mitsutoshi Ishii (M)

Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Medical-Engineering Hybrid Professional Development Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Satoshi Mizoguchi (S)

Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Medical-Engineering Hybrid Professional Development Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Ryoichiro Doi (R)

Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Koichi Tomoshige (K)

Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Tetsuji Yamaoka (T)

Department of Biomedical Engineering, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.

Takeshi Nagayasu (T)

Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Medical-Engineering Hybrid Professional Development Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

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Classifications MeSH