PMID- 30397194 OWN - NLM STAT- MEDLINE DCOM- 20190604 LR - 20200309 IS - 2092-6413 (Electronic) IS - 1226-3613 (Print) IS - 1226-3613 (Linking) VI - 50 IP - 11 DP - 2018 Nov 5 TI - Adjuvant role of macrophages in stem cell-induced cardiac repair in rats. PG - 1-10 LID - 10.1038/s12276-018-0171-5 [doi] LID - 143 AB - Bone marrow-derived mesenchymal stem cells (BMMSCs) are used extensively for cardiac repair and interact with immune cells in the damaged heart. Macrophages are known to be modulated by stem cells, and we hypothesized that priming macrophages with BMMSCs would enhance their therapeutic efficacy. Rat bone marrow-derived macrophages (BMDMs) were stimulated by lipopolysaccharide (LPS) with or without coculture with rat BMCs. In the LPS-stimulated BMDMs, induction of the inflammatory marker iNOS was attenuated, and the anti-inflammatory marker Arg1 was markedly upregulated by coculture with BMMSCs. Myocardial infarction (MI) was induced in rats. One group was injected with BMMSCs, and a second group was injected with MIX (a mixture of BMMSCs and BMDMs after coculture). The reduction in cardiac fibrosis was greater in the MIX group than in the BMC group. Cardiac function was improved in the BMMSC group and was substantially improved in the MIX group. Angiogenesis was better in the MIX group, and anti-inflammatory macrophages were more abundant in the MIX group than in the BMMSC group. In the BMMSCs, interferon regulatory factor 5 (IRF5) was exclusively induced by coculture with macrophages. IRF5 knockdown in BMMSCs failed to suppress inflammatory marker induction in the macrophages. In this study, we demonstrated the successful application of BMDMs primed with BMMSCs as an adjuvant to cell therapy for cardiac repair. FAU - Lim, Soo Yeon AU - Lim SY AD - Cell Regeneration Research Center, Chonnam National University Hospital, Gwangju, 61469, Republic of Korea. FAU - Cho, Dong Im AU - Cho DI AD - Cell Regeneration Research Center, Chonnam National University Hospital, Gwangju, 61469, Republic of Korea. FAU - Jeong, Hye-Yun AU - Jeong HY AD - Cell Regeneration Research Center, Chonnam National University Hospital, Gwangju, 61469, Republic of Korea. FAU - Kang, Hye-Jin AU - Kang HJ AD - Cell Regeneration Research Center, Chonnam National University Hospital, Gwangju, 61469, Republic of Korea. FAU - Kim, Mi Ra AU - Kim MR AD - Cell Regeneration Research Center, Chonnam National University Hospital, Gwangju, 61469, Republic of Korea. FAU - Cho, Meeyoung AU - Cho M AD - Cell Regeneration Research Center, Chonnam National University Hospital, Gwangju, 61469, Republic of Korea. FAU - Kim, Yong Sook AU - Kim YS AD - Cell Regeneration Research Center, Chonnam National University Hospital, Gwangju, 61469, Republic of Korea. retissue@jnu.ac.kr. AD - Biomedical Research Institute, Chonnam National University Hospital, Gwangju, 61469, Republic of Korea. retissue@jnu.ac.kr. FAU - Ahn, Youngkeun AU - Ahn Y AD - Cell Regeneration Research Center, Chonnam National University Hospital, Gwangju, 61469, Republic of Korea. cecilyk@hanmail.net. AD - Department of Cardiology, Chonnam National University Hospital, Gwangju, 61469, Republic of Korea. cecilyk@hanmail.net. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181105 PL - United States TA - Exp Mol Med JT - Experimental & molecular medicine JID - 9607880 RN - 0 (Culture Media, Conditioned) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 3.5.3.1 (Arginase) SB - IM MH - Animals MH - Arginase/genetics/metabolism MH - Cell Line MH - Cells, Cultured MH - Culture Media, Conditioned/pharmacology MH - Humans MH - Macrophages/*metabolism MH - Male MH - Mesenchymal Stem Cell Transplantation/*methods MH - Mesenchymal Stem Cells/drug effects/metabolism MH - Mice MH - Myocardial Infarction/*therapy MH - Nitric Oxide Synthase Type II/genetics/metabolism MH - Rats MH - Rats, Sprague-Dawley PMC - PMC6218450 COIS- The authors declare that they have no conflict of interest. EDAT- 2018/11/07 06:00 MHDA- 2019/06/05 06:00 PMCR- 2018/11/05 CRDT- 2018/11/07 06:00 PHST- 2018/04/06 00:00 [received] PHST- 2018/07/18 00:00 [accepted] PHST- 2018/07/11 00:00 [revised] PHST- 2018/11/07 06:00 [entrez] PHST- 2018/11/07 06:00 [pubmed] PHST- 2019/06/05 06:00 [medline] PHST- 2018/11/05 00:00 [pmc-release] AID - 10.1038/s12276-018-0171-5 [pii] AID - 171 [pii] AID - 10.1038/s12276-018-0171-5 [doi] PST - epublish SO - Exp Mol Med. 2018 Nov 5;50(11):1-10. doi: 10.1038/s12276-018-0171-5.