PMID- 32520222 OWN - NLM STAT- MEDLINE DCOM- 20200730 LR - 20220629 IS - 1980-5322 (Electronic) IS - 1807-5932 (Print) IS - 1807-5932 (Linking) VI - 75 DP - 2020 TI - Effects and mechanism of stem cells from human exfoliated deciduous teeth combined with hyperbaric oxygen therapy in type 2 diabetic rats. PG - e1656 LID - 10.6061/clinics/2020/e1656 [doi] LID - e1656 AB - OBJECTIVES: Mesenchymal stem cells (MSCs) are potentially ideal for type 2 diabetes treatment, owing to their multidirectional differentiation ability and immunomodulatory properties. Here we investigated whether the stem cells from human exfoliated deciduous teeth (SHED) in combination with hyperbaric oxygen (HBO) could treat type 2 diabetic rats, and explored the underlying mechanism. METHODS: SD rats were used to generate a type 2 diabetes model, which received stem cell therapy, HBO therapy, or both together. Before and after treatment, body weight, blood glucose, and serum insulin, blood lipid, pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6), and urinary proteins were measured and compared. After 6 weeks, rats were sacrificed and their organs were subjected to hematoxylin and eosin staining and immunofluorescence staining for insulin and glucagon; apoptosis and proliferation were analyzed in islet cells. Structural changes in islets were observed under an electron microscope. Expression levels of Pdx1, Ngn3, and Pax4 mRNAs in the pancreas were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: In comparison with diabetic mice, those treated with the combination or SHE therapy showed decreased blood glucose, insulin resistance, serum lipids, and pro-inflammatory cytokines and increased body weight and serum insulin. The morphology and structure of pancreatic islets improved, as evident from an increase in insulin-positive cells and a decrease in glucagon-positive cells. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining of islet cells revealed the decreased apoptosis index, while Ki67 and proliferating cell nuclear antigen staining showed increased proliferation index. Pancreatic expression of Pdx1, Ngn3, and Pax4 was upregulated. CONCLUSION: SHED combined with HBO therapy was effective for treating type 2 diabetic rats. The underlying mechanism may involve SHED-mediated increase in the proliferation and trans-differentiation of islet beta-cells and decrease in pro-inflammatory cytokines and apoptosis of islets. FAU - Xu, Yifeng AU - Xu Y AUID- ORCID: 0000-0001-9258-2690 AD - Department of Endocrinology, Changhai Hospital, the First Affiliated Hospital of the Naval Medical University, Shanghai 200433, China. AD - Department of Endocrinology, Air Force Hospital of Northern Theater Command of PLA, Shenyang 110042, China. FAU - Chen, Jin AU - Chen J AD - Department of Endocrinology, Changhai Hospital, the First Affiliated Hospital of the Naval Medical University, Shanghai 200433, China. FAU - Zhou, Hui AU - Zhou H AD - Department of Out-patient, Changning retired cadre retreat of Shanghai garrison command, Shanghai 200050, China. FAU - Wang, Jing AU - Wang J AD - Department of Endocrinology, Changhai Hospital, the First Affiliated Hospital of the Naval Medical University, Shanghai 200433, China. AD - Department of Internal Medcine, Hotan Country People's Hospital of Xinjiang, Hotan Country 848000, China. FAU - Song, Jingyun AU - Song J AD - Department of Endocrinology, Changhai Hospital, the First Affiliated Hospital of the Naval Medical University, Shanghai 200433, China. FAU - Xie, Junhao AU - Xie J AD - Department of Endocrinology, Changhai Hospital, the First Affiliated Hospital of the Naval Medical University, Shanghai 200433, China. FAU - Guo, Qingjun AU - Guo Q AD - Department of Endocrinology, Changhai Hospital, the First Affiliated Hospital of the Naval Medical University, Shanghai 200433, China. FAU - Wang, Chaoqun AU - Wang C AD - Department of Endocrinology, Changhai Hospital, the First Affiliated Hospital of the Naval Medical University, Shanghai 200433, China. FAU - Huang, Qin AU - Huang Q AUID- ORCID: 0000-0002-8678-4277 AD - Department of Endocrinology, Changhai Hospital, the First Affiliated Hospital of the Naval Medical University, Shanghai 200433, China. LA - eng PT - Journal Article DEP - 20200603 PL - United States TA - Clinics (Sao Paulo) JT - Clinics (Sao Paulo, Brazil) JID - 101244734 RN - 0 (Insulin) SB - IM MH - Animals MH - China MH - Diabetes Mellitus, Experimental/*therapy MH - Diabetes Mellitus, Type 2/chemically induced/*therapy MH - Humans MH - Hyperbaric Oxygenation/*methods MH - Insulin MH - *Insulin-Secreting Cells MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells MH - Mice MH - Rats MH - Rats, Sprague-Dawley MH - Stem Cells MH - Tooth, Deciduous PMC - PMC7247751 COIS- No potential conflict of interest was reported. EDAT- 2020/06/11 06:00 MHDA- 2020/07/31 06:00 PMCR- 2020/01/01 CRDT- 2020/06/11 06:00 PHST- 2019/11/28 00:00 [received] PHST- 2020/02/10 00:00 [accepted] PHST- 2020/06/11 06:00 [entrez] PHST- 2020/06/11 06:00 [pubmed] PHST- 2020/07/31 06:00 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - S1807-5932(22)00328-3 [pii] AID - cln_75p1 [pii] AID - 10.6061/clinics/2020/e1656 [doi] PST - epublish SO - Clinics (Sao Paulo). 2020 Jun 3;75:e1656. doi: 10.6061/clinics/2020/e1656. eCollection 2020.