PMID- 34080789 OWN - NLM STAT- MEDLINE DCOM- 20220406 LR - 20220406 IS - 2157-6580 (Electronic) IS - 2157-6564 (Print) IS - 2157-6564 (Linking) VI - 10 IP - 9 DP - 2021 Sep TI - Type 2 diabetes mellitus duration and obesity alter the efficacy of autologously transplanted bone marrow-derived mesenchymal stem/stromal cells. PG - 1266-1278 LID - 10.1002/sctm.20-0506 [doi] AB - Human bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) represent promising stem cell therapy for the treatment of type 2 diabetes mellitus (T2DM), but the results of autologous BM-MSC administration in T2DM patients are contradictory. The purpose of this study was to test the hypothesis that autologous BM-MSC administration in T2DM patient is safe and that the efficacy of the treatment is dependant on the quality of the autologous BM-MSC population and administration routes. T2DM patients were enrolled, randomly assigned (1:1) by a computer-based system into the intravenous and dorsal pancreatic arterial groups. The safety was assessed in all the treated patients, and the efficacy was evaluated based on the absolute changes in the hemoglobin A1c, fasting blood glucose, and C-peptide levels throughout the 12-month follow-up. Our data indicated that autologous BM-MSC administration was well tolerated in 30 T2DM patients. Short-term therapeutic effects were observed in patients with T2DM duration of <10 years and a body mass index <23, which is in line with the phenotypic analysis of the autologous BM-MSC population. T2DM duration directly altered the proliferation rate of BM-MSCs, abrogated the glycolysis and mitochondria respiration of BM-MSCs, and induced the accumulation of mitochondria DNA mutation. Our data suggest that autologous administration of BM-MSCs in the treatment of T2DM should be performed in patients with T2DM duration <10 years and no obesity. Prior to further confirming the effects of T2DM on BM-MSC biology, future work with a larger cohort focusing on patients with different T2DM history is needed to understand the mechanism underlying our observation. CI - (c) 2021 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press. FAU - Nguyen, Liem Thanh AU - Nguyen LT AUID- ORCID: 0000-0002-4036-0161 AD - Department of Research and Development (R&D), Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam. FAU - Hoang, Duc M AU - Hoang DM AUID- ORCID: 0000-0001-5444-561X AD - Department of Research and Development (R&D), Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam. FAU - Nguyen, Kien T AU - Nguyen KT AD - Department of Research and Development (R&D), Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam. FAU - Bui, Duc M AU - Bui DM AD - Department of Internal Medicine, Vinmec Times City International Hospital, Hanoi, Vietnam. FAU - Nguyen, Hieu T AU - Nguyen HT AD - Department of Research and Development (R&D), Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam. FAU - Le, Hong T A AU - Le HTA AD - Department of Research and Development (R&D), Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam. FAU - Hoang, Van T AU - Hoang VT AD - Department of Research and Development (R&D), Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam. FAU - Bui, Hue T H AU - Bui HTH AD - Department of Cellular Therapy, Vinmec High-Tech Center, Hanoi, Vietnam. FAU - Dam, Phuong T M AU - Dam PTM AD - Department of Cellular Therapy, Vinmec High-Tech Center, Hanoi, Vietnam. FAU - Hoang, Xuan T A AU - Hoang XTA AD - Department of Research and Development (R&D), Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam. FAU - Ngo, Anh T L AU - Ngo ATL AD - Department of Research and Development (R&D), Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam. FAU - Le, Hang M AU - Le HM AD - Department of Cellular Therapy, Vinmec High-Tech Center, Hanoi, Vietnam. FAU - Phung, Nhi Y AU - Phung NY AD - Department of Cellular Therapy, Vinmec High-Tech Center, Hanoi, Vietnam. FAU - Vu, Duc M AU - Vu DM AD - Department of Research and Development (R&D), Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam. FAU - Duong, Trung T AU - Duong TT AD - Department of Research and Development (R&D), Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam. FAU - Nguyen, Tu D AU - Nguyen TD AD - Department of Cellular Therapy, Vinmec High-Tech Center, Hanoi, Vietnam. FAU - Ha, Lien T AU - Ha LT AD - Department of Medical Genetics, Vinmec High-Tech Center, Hanoi, Vietnam. FAU - Bui, Hoa T P AU - Bui HTP AD - Department of Medical Genetics, Vinmec High-Tech Center, Hanoi, Vietnam. FAU - Nguyen, Hoa K AU - Nguyen HK AD - Department of Research and Development (R&D), Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam. FAU - Heke, Michael AU - Heke M AD - Department of Biology, Stanford University, Stanford, California, USA. FAU - Bui, Anh V AU - Bui AV AD - Department of Cellular Therapy, Vinmec High-Tech Center, Hanoi, Vietnam. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20210603 PL - England TA - Stem Cells Transl Med JT - Stem cells translational medicine JID - 101578022 SB - IM MH - Bone Marrow MH - Bone Marrow Cells MH - *Diabetes Mellitus, Type 2/metabolism/therapy MH - Humans MH - *Mesenchymal Stem Cell Transplantation/adverse effects/methods MH - *Mesenchymal Stem Cells/metabolism MH - Obesity/metabolism PMC - PMC8380443 OTO - NOTNLM OT - autologous OT - autologous stem cell transplantation OT - bone marrow OT - diabetes COIS- The authors indicated no potential conflicts of interest. EDAT- 2021/06/04 06:00 MHDA- 2022/04/07 06:00 PMCR- 2021/06/03 CRDT- 2021/06/03 08:56 PHST- 2021/03/11 00:00 [revised] PHST- 2020/11/14 00:00 [received] PHST- 2021/04/08 00:00 [accepted] PHST- 2021/06/04 06:00 [pubmed] PHST- 2022/04/07 06:00 [medline] PHST- 2021/06/03 08:56 [entrez] PHST- 2021/06/03 00:00 [pmc-release] AID - SCT312969 [pii] AID - 10.1002/sctm.20-0506 [doi] PST - ppublish SO - Stem Cells Transl Med. 2021 Sep;10(9):1266-1278. doi: 10.1002/sctm.20-0506. Epub 2021 Jun 3.