PMID- 33623636 OWN - NLM STAT- MEDLINE DCOM- 20210909 LR - 20240226 IS - 1942-0994 (Electronic) IS - 1942-0900 (Print) IS - 1942-0994 (Linking) VI - 2021 DP - 2021 TI - Antioxidative Capacity of Liver- and Adipose-Derived Mesenchymal Stem Cell-Conditioned Media and Their Applicability in Treatment of Type 2 Diabetic Rats. PG - 8833467 LID - 10.1155/2021/8833467 [doi] LID - 8833467 AB - Type 2 diabetes mellitus (T2DM) is mainly characterized by insulin resistance and impaired insulin secretion, which cannot be reversed with existing therapeutic strategies. Using mesenchymal stem cells (MSCs), cell-based therapy has been demonstrated in displaying therapeutic effects in T2DM for their self-renewable, differentiation potential, and immunosuppressive properties and higher levels of angiogenic factors. Stem cell therapies are complicated and have a serious adverse effect including tumor formation and immunogenicity, while using mesenchymal stem cell-conditioned media (MSC-CM) significantly reduces stem cell risk, maintaining efficacy and showing significantly higher levels of growth factors, cytokines, and angiogenic factors that stimulate angiogenesis and promote fracture healing in diabetes. In the present study, we investigated the therapeutic potential of the liver and adipose MSC-CM in diabetic endothelial dysfunction compared with standard insulin therapy. Fifty adult male Sprague Dawley rats were divided equally into 5 groups as follows: control, diabetic, diabetic+insulin, diabetic+liver MSC-CM, and diabetic+adipose MSC-CM; all treatments continued for 4 weeks. Finally, we observed that liver MSC-CM therapy had the most apparent improvement in levels of blood glucose; HbA1c; AGEs; lipid panel (cholesterol, TG, LDL, HDL, and total lipids); renal function (urea, uric acid, creatinine, and total protein); liver function (AST, ALT, ALP, bilirubin, and albumin); CPK; C-peptide; HO-1; inflammatory markers including IL-6, TNF-alpha, and CRP; growth factors (liver and serum IGF-1); amylase; histopathological changes; pancreatic cell oxidative stress; and antioxidant markers (MDA, GSH, ROS, CAT, SOD, HO-1, and XO) toward the normal levels compared with insulin and adipose MSCs-CM. Moreover, both the liver and adipose MSC-CM relieved the hyperglycemic status by improving pancreatic islet beta cell regeneration, promoting the conversion of alpha cells to beta cells, reducing insulin resistance, and protecting pancreatic tissues against oxidative stress-induced injury as well as possessing the ability to modulate immunity and angiogenesis. These results indicated that MSC-CM infusion has therapeutic effects in T2DM rats and may be a promising novel therapeutic target. CI - Copyright (c) 2021 Mohamed M. Elshemy et al. FAU - Elshemy, Mohamed M AU - Elshemy MM AUID- ORCID: 0000-0002-6279-7559 AD - Faculty of Science, Menoufia University, Menoufia, Egypt. FAU - Asem, Medhat AU - Asem M AD - Faculty of Science, Menoufia University, Menoufia, Egypt. FAU - Allemailem, Khaled S AU - Allemailem KS AUID- ORCID: 0000-0002-6486-9835 AD - Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia. FAU - Uto, Koichiro AU - Uto K AUID- ORCID: 0000-0001-7091-0585 AD - Research Center for Functional Materials, National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan. FAU - Ebara, Mitsuhiro AU - Ebara M AUID- ORCID: 0000-0002-7906-0350 AD - Research Center for Functional Materials, National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan. AD - Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan. AD - Graduate School of Industrial Science and Technology, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-8585, Japan. FAU - Nabil, Ahmed AU - Nabil A AUID- ORCID: 0000-0002-5617-4726 AD - Research Center for Functional Materials, National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan. AD - Biotechnology and Life Sciences Department, Faculty of Postgraduate Studies for Advanced Sciences (PSAS), Beni-Suef University, Beni-Suef, Egypt. LA - eng PT - Journal Article PT - Retracted Publication DEP - 20210202 PL - United States TA - Oxid Med Cell Longev JT - Oxidative medicine and cellular longevity JID - 101479826 RN - 0 (Antioxidants) RN - 0 (Biomarkers) RN - 0 (Culture Media, Conditioned) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Lipids) SB - IM RIN - Oxid Med Cell Longev. 2024 Jan 9;2024:9854014. PMID: 38234531 MH - Adipose Tissue/*cytology MH - Animals MH - Antioxidants/*pharmacology MH - Biomarkers/metabolism MH - Culture Media, Conditioned/*pharmacology MH - Diabetes Mellitus, Experimental/complications/*drug therapy/pathology MH - Diabetes Mellitus, Type 2/complications/*drug therapy/pathology MH - Inflammation/complications/pathology MH - Intercellular Signaling Peptides and Proteins/metabolism MH - Kidney/drug effects/physiopathology MH - Lipids/blood MH - Liver/*cytology/physiopathology MH - Male MH - Mesenchymal Stem Cells/drug effects/*metabolism MH - Myocardium/enzymology/pathology MH - Oxidative Stress/drug effects MH - Pancreas/pathology MH - Rats, Sprague-Dawley MH - Rats PMC - PMC7875634 COIS- The authors declare that they have no conflict of interest. EDAT- 2021/02/25 06:00 MHDA- 2021/09/10 06:00 PMCR- 2021/02/02 CRDT- 2021/02/24 05:44 PHST- 2020/09/09 00:00 [received] PHST- 2021/01/08 00:00 [revised] PHST- 2021/01/21 00:00 [accepted] PHST- 2021/02/24 05:44 [entrez] PHST- 2021/02/25 06:00 [pubmed] PHST- 2021/09/10 06:00 [medline] PHST- 2021/02/02 00:00 [pmc-release] AID - 10.1155/2021/8833467 [doi] PST - epublish SO - Oxid Med Cell Longev. 2021 Feb 2;2021:8833467. doi: 10.1155/2021/8833467. eCollection 2021.