PMID- 32778240 OWN - NLM STAT- MEDLINE DCOM- 20210621 LR - 20210621 IS - 1618-0372 (Electronic) IS - 0065-1281 (Linking) VI - 122 IP - 6 DP - 2020 Sep TI - Umbilical cord mesenchymal stromal cells engraft and transdifferentiate into cardiomyocyte-like cells following acute myocardial ischemia small star, filled. PG - 151578 LID - S0065-1281(20)30077-5 [pii] LID - 10.1016/j.acthis.2020.151578 [doi] AB - OBJECTIVE: Human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) gained importance in acute/chronic ischemic cardiomyopathy because of their outstanding regenerative potential in various pathologic conditions. The present study was designed to determine to what extent hUC-MSCs contribute to myocardial regeneration in acute experimental myocardial infarction (MI) in rats. METHODS: Animals were assigned into two groups; the control group received intramyocardial PBS injections, while the hUC-MSC group received calcein-AM-labeled 8.8 x 10(6)/kg hUC-MSCs. Three weeks following the acute MI induction, rats were sacrificed after assessing the left ventricular (LV) function using echocardiography. For the assessment of infarct size, the triphenyl tetrazolium chloride (TTC) test was used in isolated hearts. Collagen-rich scar tissue was demonstrated using Masson's trichrome staining, followed by the detection of cardiac troponin I (cTnI), alpha-sarcomeric actin (alpha-SA), von Willebrand factor (vWF), CD68 and CD206 expressions in control and cell-injected sections. RESULTS: Echocardiography revealed a significant difference (P = 0.037) in the LV ejection fraction between groups. TTC assays demonstrated a significant difference (P = 0.006) between the groups regarding the ratio of the infarcted LV area. Calcein-AM-loaded cells were identified mostly in ischemic myocardium. Transplanted cells also expressed human-specific cTnI, providing concrete proof of transdifferentiation into cardiomyocytes, and alpha-SA. vWF(+) cells verified the neovascularization in the ischemic myocardium. Finally, a slight shift from pro-inflammatory to anti-inflammatory macrophages (CD68(+)/CD206(+)) was noted in both groups. CONCLUSIONS: We found that the intramyocardial transplanted hUC-MSCs engrafted and partially transdifferentiated into cardiomyocytes, reduced scar formation, and induced angiogenesis through the association of pro/anti-inflammatory macrophages. CI - Copyright (c) 2020 Elsevier GmbH. All rights reserved. FAU - Yigman, Zeynep AU - Yigman Z AD - Gazi University Faculty of Medicine, Department of Histology and Embryology, Yenimahalle, Ankara, 06560, Turkey. Electronic address: zeynepyigman@gazi.edu.tr. FAU - Ozdemir, Elif Derya AU - Ozdemir ED AD - Gazi University Faculty of Pharmacy, Department of Pharmacology, Yenimahalle, Ankara, 06560, Turkey. Electronic address: elif.derya.ozdemir@gmail.com. FAU - Turan, Nilufer N AU - Turan NN AD - Cardiovascular Research Center, Division of Cardiology, Rhode Island Hospital, Warren Alpert School of Brown University, Providence, RI, 02903, USA. Electronic address: nilufer_turan_durel@brown.edu. FAU - Ulus, A Tulga AU - Ulus AT AD - Hacettepe University Faculty of Medicine, Department of Cardiovascular and Thoracic Surgery, Sihhiye, Ankara, 06100, Turkey. Electronic address: uluss@yahoo.com. FAU - Can, Alp AU - Can A AD - Ankara University School of Medicine, Department of Histology and Embryology, Laboratories for Stem Cells and Reproductive Medicine, Sihhiye, Ankara, 06100, Turkey. Electronic address: alpcan@medicine.ankara.edu.tr. LA - eng PT - Journal Article DEP - 20200702 PL - Germany TA - Acta Histochem JT - Acta histochemica JID - 0370320 SB - IM MH - Animals MH - Cells, Cultured MH - Echocardiography MH - Female MH - Humans MH - Immunohistochemistry MH - Male MH - Mesenchymal Stem Cells/*cytology/metabolism MH - Myocardial Ischemia/*metabolism/*pathology MH - Myocytes, Cardiac/*cytology/metabolism MH - Neovascularization, Physiologic/physiology MH - Pregnancy MH - Rats MH - Rats, Wistar MH - Umbilical Cord/*cytology OTO - NOTNLM OT - Cardiac regeneration OT - Cell therapy OT - Human umbilical cord-derived mesenchymal stromal cells OT - Myocardial ischemia OT - Rat COIS- Declaration of Competing Interest The authors declare that they have no conflict of interest. EDAT- 2020/08/12 06:00 MHDA- 2021/06/22 06:00 CRDT- 2020/08/12 06:00 PHST- 2020/03/30 00:00 [received] PHST- 2020/06/17 00:00 [revised] PHST- 2020/06/19 00:00 [accepted] PHST- 2020/08/12 06:00 [entrez] PHST- 2020/08/12 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] AID - S0065-1281(20)30077-5 [pii] AID - 10.1016/j.acthis.2020.151578 [doi] PST - ppublish SO - Acta Histochem. 2020 Sep;122(6):151578. doi: 10.1016/j.acthis.2020.151578. Epub 2020 Jul 2.