PMID- 35729660 OWN - NLM STAT- MEDLINE DCOM- 20220623 LR - 20220729 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 13 IP - 1 DP - 2022 Jun 21 TI - Dose-dependent benefits of iron-magnetic nanoparticle-coated human umbilical-derived mesenchymal stem cell treatment in rat intracranial hemorrhage model. PG - 265 LID - 10.1186/s13287-022-02939-4 [doi] LID - 265 AB - BACKGROUND: This study tested whether two doses of human umbilical-derived mesenchymal stem cells (hUC-MSCs) were superior to one dose for protecting the brain against intracranial hemorrhage (ICH) induced by intracranial injection collagenase and the capacity of ironic-magnetic-nanoparticles (Ir-MNa) coated hUC-MSCs tracked by MRI. METHODS AND RESULTS: Adult male SD rats (n = 40) were equally categorized into group 1 (sham-operated-control), group 2 (ICH), group 3 [ICH + Ir-MNa-coated hUC-MSCs/1.2 x 10(6) cells with an extracorporeal magnet over rat head (eCMag)/administered by left internal carotid artery (LICA) at post-3 h ICH], and group 4 (ICH + Ir-MNa-coated hUC-MSCs/1.2 x 10(6) cells with an eCMag/administered post-3 h ICH by LICA and 24 h by IV) and euthanized by day 28. The result showed that by day 28 after ICH induction the neurological function was severely impaired in group 2 than in group 1 that was significantly improved in group 3 and further significantly improved in group 4, whereas ICH volume exhibited an opposite pattern of neurological impairment among the groups (all p < 0.0001). Brain MRI demonstrated that by 4 h after ICH, Ir-MNa-coated hUC-MSCs were abundantly identified in ischemic area in group 4. The protein expressions of inflammatory (TNF-alpha/MMP-9/IL-1ss/iNOS)/oxidative-stress (NOX-1/NOX-2/oxidized protein)/apoptotic (caspase-3/mitochondrial Bax/PARP)/fibrotic (Smad3/TGF-ss)/mitochondrial-damaged (cytosolic-cytochrome-C) biomarkers displayed an identical pattern of neurological impairment among the groups (all p < 0.0001). The cellular expressions of inflammation (CD68+/CD11b+)/brain edema (AQP4+) biomarkers exhibited an identical pattern, whereas the neuronal-myelin (Doublecortin+/NeuN/nestin) biomarkers displayed an opposite pattern of neurological impairment (all p < 0.0001). CONCLUSION: Two doses of hUC-MSCs were superior to just one dose for protecting the brain against ICH-induced damage and Ir-MNa-coated hUC-MSCs offered a well adopted method for tracking hUC-MSCs homing into the brain. CI - (c) 2022. The Author(s). FAU - Chen, Kuan-Hung AU - Chen KH AD - Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan, ROC. AD - Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan, ROC. FAU - Chai, Han-Tan AU - Chai HT AD - Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan, ROC. FAU - Lin, Kun-Chen AU - Lin KC AD - Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan, ROC. FAU - Chiang, John Y AU - Chiang JY AD - Department of Computer Science and Engineering, National Sun Yat-Sen University, Kaohsiung, 80424, Taiwan, ROC. FAU - Sung, Pei-Hsun AU - Sung PH AD - Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan, ROC. AD - Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan, ROC. AD - Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan, ROC. FAU - Chen, Chih-Hung AU - Chen CH AD - Divisions of General Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan, ROC. FAU - Yip, Hon-Kan AU - Yip HK AUID- ORCID: 0000-0002-6305-5717 AD - Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan, ROC. han.gung@msa.hinet.net. AD - Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan, ROC. han.gung@msa.hinet.net. AD - Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan, ROC. han.gung@msa.hinet.net. AD - School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC. han.gung@msa.hinet.net. AD - Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 40402, Taiwan, ROC. han.gung@msa.hinet.net. AD - Department of Nursing, Asia University, Taichung, 41354, Taiwan, ROC. han.gung@msa.hinet.net. AD - Division of Cardiology, Department of Internal Medicine, Xiamen Chang Gung Hospital, Xiamen, 361028, Fujian, China. han.gung@msa.hinet.net. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220621 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 RN - 0 (Biomarkers) RN - 0 (Magnetite Nanoparticles) RN - E1UOL152H7 (Iron) SB - IM MH - Animals MH - Biomarkers/metabolism MH - Humans MH - Intracranial Hemorrhages/metabolism/therapy MH - Iron/metabolism MH - *Magnetite Nanoparticles MH - Male MH - *Mesenchymal Stem Cell Transplantation/methods MH - *Mesenchymal Stem Cells/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Umbilical Cord/metabolism PMC - PMC9210819 OTO - NOTNLM OT - Brain infarct volume OT - Inflammatory reaction OT - Intracranial hemorrhage OT - Mesenchymal stem cells OT - Neurological impairment COIS- The authors declare that they have no conflict of interest. EDAT- 2022/06/22 06:00 MHDA- 2022/06/24 06:00 PMCR- 2022/06/21 CRDT- 2022/06/21 23:46 PHST- 2021/11/06 00:00 [received] PHST- 2022/06/05 00:00 [accepted] PHST- 2022/06/21 23:46 [entrez] PHST- 2022/06/22 06:00 [pubmed] PHST- 2022/06/24 06:00 [medline] PHST- 2022/06/21 00:00 [pmc-release] AID - 10.1186/s13287-022-02939-4 [pii] AID - 2939 [pii] AID - 10.1186/s13287-022-02939-4 [doi] PST - epublish SO - Stem Cell Res Ther. 2022 Jun 21;13(1):265. doi: 10.1186/s13287-022-02939-4.