PMID- 31830131 OWN - NLM STAT- MEDLINE DCOM- 20200326 LR - 20200326 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 14 IP - 12 DP - 2019 TI - Verification of mesenchymal stem cell injection therapy for interstitial cystitis in a rat model. PG - e0226390 LID - 10.1371/journal.pone.0226390 [doi] LID - e0226390 AB - OBJECTIVE: Interstitial cystitis (IC) is a chronic intractable disease. Recently, the potential application of stem cell (SC) therapy was suggested for IC management. This study aimed to establish an optimal SC source and verify the efficacy and safety of SC injection therapy in an IC rat model. DESIGN: After IC animal model induction, urine-derived stem cells (USCs), adipose tissue-derived stem cells (ADSCs), bone marrow-derived stem cells (BMSCs) and amniotic fluid-derived stem cells (AFSCs) were injected into the bladder submucosa. The following parameters were analysed: 1) functional improvement of bladder via cystometry, 2) histological changes and 3) inflammatory gene expression and regenerative potential of damaged bladder tissues. Additionally, an optimal method for SC introduction in terms of effective bladder regeneration was analysed. RESULTS: Intercontraction interval was significantly increased and inflammatory reactions and fibrotic changes were decreased in all of the SC-injected groups than in the control group. PCR analysis revealed that inflammatory gene expression significantly decreased in the USC-treated group than in the other groups. To confirm the optimal SC injection route in the IC rat model, group was divided according to the following criteria: 1) direction of SC injection into the bladder submucosa, 2) injection via tail vein, 3) transurethral instillation. In each analysis, the groups in which SCs were injected into the bladder submucosa showed significantly longer intercontraction interval, better morphologic regeneration and inhibition of bladder inflammatory reaction compared with the other groups. CONCLUSION: Regardless of the cell source, human tissue-derived mesenchymal SCs regenerated damaged bladder tissue, promoted functional recovery and inhibited inflammatory cell accumulation in an IC rat model; particularly, USC had the highest inhibitory effect on inflammation. Additionally, direct USC injection into the bladder submucosa was expected to have the best therapeutic effect, which will be an important factor for clinical applications in the future. FAU - Chung, Jae-Wook AU - Chung JW AUID- ORCID: 0000-0002-1055-2357 AD - Department of Urology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea. FAU - Chun, So Young AU - Chun SY AD - BioMedical Research Institute, Joint Institute for Regenerative Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea. FAU - Lee, Eun Hye AU - Lee EH AD - Department of Pathology, School of Medicine, Kyungpook National University, Daegu, South Korea. FAU - Ha, Yun-Sok AU - Ha YS AD - Department of Urology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea. AD - Joint Institute for Regenerative Medicine, Kyungpook National University, Daegu, Republic of Korea. FAU - Lee, Jun Nyung AU - Lee JN AD - Department of Urology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea. AD - Joint Institute for Regenerative Medicine, Kyungpook National University, Daegu, Republic of Korea. FAU - Song, Phil Hyun AU - Song PH AD - Department of Urology, Yeungnam University College of Medicine, Daegu, Republic of Korea. FAU - Yoo, Eun Sang AU - Yoo ES AD - Department of Urology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea. FAU - Kwon, Tae Gyun AU - Kwon TG AD - Department of Urology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea. AD - Joint Institute for Regenerative Medicine, Kyungpook National University, Daegu, Republic of Korea. FAU - Chung, Sung Kwang AU - Chung SK AD - Department of Urology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea. FAU - Kim, Bum Soo AU - Kim BS AUID- ORCID: 0000-0002-4873-3049 AD - Joint Institute for Regenerative Medicine, Kyungpook National University, Daegu, Republic of Korea. AD - Department of Urology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191212 PL - United States TA - PLoS One JT - PloS one JID - 101285081 SB - IM CIN - J Urol. 2020 Aug;204(2):389-390. PMID: 32396436 MH - Animals MH - Cells, Cultured MH - Cystitis, Interstitial/*therapy MH - Disease Models, Animal MH - Female MH - Mesenchymal Stem Cell Transplantation/*methods MH - Mesenchymal Stem Cells/*cytology MH - Rats MH - Rats, Sprague-Dawley MH - *Recovery of Function MH - Regeneration PMC - PMC6907861 COIS- The authors have declared that no competing interests exist. EDAT- 2019/12/13 06:00 MHDA- 2020/03/27 06:00 PMCR- 2019/12/12 CRDT- 2019/12/13 06:00 PHST- 2019/08/21 00:00 [received] PHST- 2019/11/25 00:00 [accepted] PHST- 2019/12/13 06:00 [entrez] PHST- 2019/12/13 06:00 [pubmed] PHST- 2020/03/27 06:00 [medline] PHST- 2019/12/12 00:00 [pmc-release] AID - PONE-D-19-23541 [pii] AID - 10.1371/journal.pone.0226390 [doi] PST - epublish SO - PLoS One. 2019 Dec 12;14(12):e0226390. doi: 10.1371/journal.pone.0226390. eCollection 2019.