PMID- 35841116 OWN - NLM STAT- MEDLINE DCOM- 20220719 LR - 20221021 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 13 IP - 1 DP - 2022 Jul 15 TI - The therapeutic effect of stem cells from human exfoliated deciduous teeth on a rat model of tracheal fistula. PG - 310 LID - 10.1186/s13287-022-02994-x [doi] LID - 310 AB - BACKGROUND: Tracheal fistulas (TF) can be dangerous and even fatal in patients. The current treatment is really challenging. Previous studies reported that mesenchymal stem cells (MSCs) could be used to treat respiratory tract fistulas. Stem cells from human exfoliated deciduous teeth (SHED) are considered to be MSC-like cells that may also have the potential to treat the tracheal fistulas. In this study, we investigated the therapeutic effects of SHED in rat tracheal fistula models. METHODS: A total of 80 SD rats were randomly divided into five groups: a sham-operated group, a local PBS group (L-PBS), an intravenous PBS group (I-PBS), a local SHED treatment group (L-SHED), and an intravenous SHED treatment group (I-SHED). The L-SHED and I-SHED groups were given a topical application around the fistula or an intravenous injection of 1*10(7) SHED via the tail vein, respectively, while the L-PBS and I-PBS groups were given an equivalent volume of PBS through local or intravenous administration. A stereomicroscope was used to observe fistula healing on the 2nd, 3rd, and 5th days following transplantation. On the 7th day, the survival of SHED was observed by immunofluorescence. The pathology of the lungs and fistulas was observed by hematoxylin and eosin (H&E) and Masson staining. The expression levels of the Toll-like receptor 4 (TLR4), interleukin (IL)-1beta, IL-33, and IL-4 were measured using immunohistochemistry. The expression levels of TLR4, high mobility group box 1 (HMGB1), and myeloid differentiation factor 88 (MYD88) were studied using western blotting. On day 14, airway responsiveness of rats was detected and analyzed. RESULTS: Fistula healing in the L-SHED and I-SHED groups was faster than that in their respective PBS groups after transplantation. The fistula diameters in the L-SHED and I-SHED groups were significantly smaller than those in the L-PBS and I-PBS groups on the 3rd day. Moreover, the phenomenon of fibroblast proliferation and new blood vessel growth around the fistula seemed more pronounced in the L-SHED and I-SHED groups. Although no discernible difference was found in airway responsiveness after SHED treatment, the degree of inflammation in the lungs was reduced by intravenous SHED treatment. However, there was no significant reduction in lung inflammation by local SHED treatment. The expression levels of IL-1beta and IL-33 were decreased in the I-SHED group, while IL-4 was elevated compared with the I-PBS group. Interestingly, intravenous SHED treatment inhibited the activation of HMGB1/TLR4/MYD88 in the lung tissues of TF rats. CONCLUSIONS: SHED transplantation accelerated the rate of fistula healing in rats. Intravenous SHED treatment reduced lung inflammation. Thus, SHED may have potential in the treatment of tracheal fistula, providing hope for future therapeutic development for TF. CI - (c) 2022. The Author(s). FAU - Wang, Fang AU - Wang F AD - School of Medicine, South China University of Technology, Guangzhou, 510006, China. AD - Second Department of Elderly Respiratory, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, Guangzhou, 510080, China. FAU - Li, Zhangwen AU - Li Z AD - School of Medicine, South China University of Technology, Guangzhou, 510006, China. AD - Second Department of Elderly Respiratory, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, Guangzhou, 510080, China. FAU - Lyu, Feng-Juan AU - Lyu FJ AD - School of Medicine, South China University of Technology, Guangzhou, 510006, China. FAU - Gao, Jie AU - Gao J AD - Second Department of Elderly Respiratory, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, Guangzhou, 510080, China. AD - The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China. FAU - Lin, Jinle AU - Lin J AD - The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China. AD - Department of Emergency Medicine, Affiliated Baoan Hospital of Shenzhen, The second school of clinical medicine, Southern Medical University, Shenzhen, 518101, China. FAU - Liu, Jianling AU - Liu J AD - School of Medicine, South China University of Technology, Guangzhou, 510006, China. AD - Second Department of Elderly Respiratory, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, Guangzhou, 510080, China. FAU - Chen, Xiaowen AU - Chen X AD - School of Medicine, South China University of Technology, Guangzhou, 510006, China. AD - Second Department of Elderly Respiratory, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, Guangzhou, 510080, China. FAU - Li, Zhongpeng AU - Li Z AD - Second Department of Elderly Respiratory, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, Guangzhou, 510080, China. AD - The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China. FAU - Shan, Jiajie AU - Shan J AD - School of Medicine, South China University of Technology, Guangzhou, 510006, China. FAU - Wu, Jian AU - Wu J AD - School of Medicine, South China University of Technology, Guangzhou, 510006, China. sywujian@scut.edu.cn. AD - Second Department of Elderly Respiratory, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, Guangzhou, 510080, China. sywujian@scut.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220715 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 RN - 0 (HMGB1 Protein) RN - 0 (Interleukin-33) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (Toll-Like Receptor 4) RN - 207137-56-2 (Interleukin-4) SB - IM EIN - Stem Cell Res Ther. 2022 Oct 20;13(1):506. PMID: 36266664 MH - Animals MH - *HMGB1 Protein/metabolism MH - Humans MH - Interleukin-33/metabolism MH - Interleukin-4/metabolism MH - Myeloid Differentiation Factor 88/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - *Respiratory Tract Fistula MH - Stem Cells/metabolism MH - Toll-Like Receptor 4/genetics/metabolism MH - Tooth, Deciduous PMC - PMC9284811 OTO - NOTNLM OT - Cell therapy OT - MSCs OT - Stem cells from human exfoliated deciduous teeth OT - Tracheal fistula COIS- The authors declare that they have no competing interests. EDAT- 2022/07/16 06:00 MHDA- 2022/07/20 06:00 PMCR- 2022/07/15 CRDT- 2022/07/15 23:51 PHST- 2022/01/06 00:00 [received] PHST- 2022/06/28 00:00 [accepted] PHST- 2022/07/15 23:51 [entrez] PHST- 2022/07/16 06:00 [pubmed] PHST- 2022/07/20 06:00 [medline] PHST- 2022/07/15 00:00 [pmc-release] AID - 10.1186/s13287-022-02994-x [pii] AID - 2994 [pii] AID - 10.1186/s13287-022-02994-x [doi] PST - epublish SO - Stem Cell Res Ther. 2022 Jul 15;13(1):310. doi: 10.1186/s13287-022-02994-x.