#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Verification of mesenchymal stem cell injection therapy for interstitial cystitis in a rat model


Autoři: Jae-Wook Chung aff001;  So Young Chun aff002;  Eun Hye Lee aff003;  Yun-Sok Ha aff001;  Jun Nyung Lee aff001;  Phil Hyun Song aff005;  Eun Sang Yoo aff006;  Tae Gyun Kwon aff001;  Sung Kwang Chung aff006;  Bum Soo Kim aff004
Působiště autorů: Department of Urology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea aff001;  BioMedical Research Institute, Joint Institute for Regenerative Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea aff002;  Department of Pathology, School of Medicine, Kyungpook National University, Daegu, South Korea aff003;  Joint Institute for Regenerative Medicine, Kyungpook National University, Daegu, Republic of Korea aff004;  Department of Urology, Yeungnam University College of Medicine, Daegu, Republic of Korea aff005;  Department of Urology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea aff006
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0226390

Souhrn

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.

Klíčová slova:

Bladder – Gene expression – Histology – Immunohistochemistry techniques – Inflammation – Mesenchymal stem cells – Stem cell therapy – Mast cells


Zdroje

1. Bogart LM, Berry SH, Clemens JQ. Symptoms of interstitial cystitis, painful bladder syndrome and similar diseases in women: a systematic review. J Urol. 2007;177(2):450–6. doi: 10.1016/j.juro.2006.09.032 17222607.

2. Chancellor MB, Yoshimura N. Treatment of interstitial cystitis. Urology. 2004;63(3 Suppl 1):85–92. doi: 10.1016/j.urology.2003.10.034 15013658.

3. Berry SH, Elliott MN, Suttorp M, Bogart LM, Stoto MA, Eggers P, et al. Prevalence of symptoms of bladder pain syndrome/interstitial cystitis among adult females in the United States. J Urol. 2011;186(2):540–4. doi: 10.1016/j.juro.2011.03.132 21683389.

4. Phatak S, Foster HE Jr. The management of interstitial cystitis: an update. Nat Clin Pract Urol. 2006;3(1):45–53. doi: 10.1038/ncpuro0385 16474494.

5. Hanno P, Keay S, Moldwin R, Van Ophoven A. International Consultation on IC—Rome, September 2004/Forging an International Consensus: progress in painful bladder syndrome/interstitial cystitis. Report and abstracts. Int Urogynecol J Pelvic Floor Dysfunct. 2005;16 Suppl 1:S2–S34. doi: 10.1007/s00192-005-1301-x 15883858.

6. Kim A, Shin DM, Choo MS. Stem Cell Therapy for Interstitial Cystitis/Bladder Pain Syndrome. Curr Urol Rep. 2016;17(1):1. doi: 10.1007/s11934-015-0563-1 26686192.

7. Nordling J. Interstitial cystitis: how should we diagnose it and treat it in 2004? Curr Opin Urol. 2004;14(6):323–7. doi: 10.1097/00042307-200411000-00005 15626873

8. Sand PK. Proposed pathogenesis of painful bladder syndrome/interstitial cystitis. J Reprod Med. 2006;51(3 Suppl):234–40. 16676918.

9. Kim A, Hoe KO, Shin JH, Choo MS. Evaluation of the incidence and risk factors associated with persistent frequency in interstitial cystitis/bladder pain syndrome and the efficacy of antimuscarinic treatment. Investig Clin Urol. 2017;58(5):353–8. doi: 10.4111/icu.2017.58.5.353 28868507.

10. Adamowicz J, Pokrywczynska M, Drewa T. Conditioned medium derived from mesenchymal stem cells culture as a intravesical therapy for cystitis interstitials. Med Hypotheses. 2014;82(6):670–3. Epub 2014/04/01. doi: 10.1016/j.mehy.2014.02.027 24679668.

11. Song M, Lim J, Yu HY, Park J, Chun JY, Jeong J, et al. Mesenchymal Stem Cell Therapy Alleviates Interstitial Cystitis by Activating Wnt Signaling Pathway. Stem Cells Dev. 2015;24(14):1648–57. doi: 10.1089/scd.2014.0459 25745847.

12. Ryu CM, Yu HY, Lee HY, Shin JH, Lee S, Ju H, et al. Longitudinal intravital imaging of transplanted mesenchymal stem cells elucidates their functional integration and therapeutic potency in an animal model of interstitial cystitis/bladder pain syndrome. Theranostics. 2018;8(20):5610–24. doi: 10.7150/thno.27559 30555567

13. El-Hamamsy D. Bladder wall injection of mesenchymal stem cells ameliorates bladder inflammation, overactivity and nociception in a chemically induced interstitial cystitis-like rat model. Int Urogynecol J. 2018. doi: 10.1007/s00192-018-3631-5 29600399.

14. Lin CS. Stem Cell Therapy for the Bladder-Where Do We Stand? J Urology. 2011;185(3):779–80. doi: 10.1016/j.juro.2010.12.014 21239018

15. Maumus M, Guerit D, Toupet K, Jorgensen C, Noel D. Mesenchymal stem cell-based therapies in regenerative medicine: applications in rheumatology. Stem Cell Res Ther. 2011;2(2):14. doi: 10.1186/scrt55 21457518.

16. Wang D, Li J, Zhang Y, Zhang M, Chen J, Li X, et al. Umbilical cord mesenchymal stem cell transplantation in active and refractory systemic lupus erythematosus: a multicenter clinical study. Arthritis Res Ther. 2014;16(2):R79. doi: 10.1186/ar4520 24661633.

17. Song PH, Chun SY, Chung JW, Kim YY, Lee HJ, Lee JN, et al. Comparison of 5 Different Rat Models to Establish a Standard Animal Model for Research Into Interstitial Cystitis. International Neurourology Journal. 2017;21(3):163–70. doi: 10.5213/inj.1734898.449 28954463

18. Chun SY, Kim HT, Lee JS, Kim MJ, Kim BS, Kim BW, et al. Characterization of urine-derived cells from upper urinary tract in patients with bladder cancer. Urology. 2012;79(5):1186 e1–7. doi: 10.1016/j.urology.2011.12.034 22381247.

19. Kim BS, Chun SY, Lee JK, Lim HJ, Bae JS, Chung HY, et al. Human amniotic fluid stem cell injection therapy for urethral sphincter regeneration in an animal model. BMC Med. 2012;10:94. doi: 10.1186/1741-7015-10-94 22906045.

20. Lee SY, Lim J, Khang G, Son Y, Choung PH, Kang SS, et al. Enhanced ex vivo expansion of human adipose tissue-derived mesenchymal stromal cells by fibroblast growth factor-2 and dexamethasone. Tissue Eng Part A. 2009;15(9):2491–9. doi: 10.1089/ten.tea.2008.0465 19292683.

21. Sant GR, Theoharides TC. The role of the mast cell in interstitial cystitis. Urol Clin North Am. 1994;21(1):41–53. 8284844.

22. Church MK, Lowman MA, Rees PH, Benyon RC. Mast cells, neuropeptides and inflammation. Agents Actions. 1989;27(1–2):8–16. doi: 10.1007/bf02222185 2473641.

23. van de Merwe JP. Interstitial cystitis and systemic autoimmune diseases. Nat Clin Pract Urol. 2007;4(9):484–91. doi: 10.1038/ncpuro0874 17823601.

24. Johansson SL, Fall M. Clinical features and spectrum of light microscopic changes in interstitial cystitis. J Urol. 1990;143(6):1118–24. doi: 10.1016/s0022-5347(17)40201-1 2342171.

25. Ratajczak MZ, Machalinski B, Wojakowski W, Ratajczak J, Kucia M. A hypothesis for an embryonic origin of pluripotent Oct-4(+) stem cells in adult bone marrow and other tissues. Leukemia. 2007;21(5):860–7. doi: 10.1038/sj.leu.2404630 17344915.

26. Wezel F, Southgate J, Thomas DF. Regenerative medicine in urology. Bju Int. 2011;108(7):1046–65. doi: 10.1111/j.1464-410X.2011.10206.x 21895928.

27. Maltais S, Tremblay JP, Perrault LP, Ly HQ. The paracrine effect: pivotal mechanism in cell-based cardiac repair. J Cardiovasc Transl Res. 2010;3(6):652–62. doi: 10.1007/s12265-010-9198-2 20559770.

28. Wang M, Yuan Q, Xie L. Mesenchymal Stem Cell-Based Immunomodulation: Properties and Clinical Application. Stem Cells Int. 2018;2018:3057624. doi: 10.1155/2018/3057624 30013600.

29. Adamowicz J, Pokrywczynska M, Drewa T. Conditioned medium derived from mesenchymal stem cells culture as a intravesical therapy for cystitis interstitials. Med Hypotheses. 2014;82(6):670–3. doi: 10.1016/j.mehy.2014.02.027 24679668

30. Korbling M, Estrov Z. Adult stem cells for tissue repair—a new therapeutic concept? N Engl J Med. 2003;349(6):570–82. doi: 10.1056/NEJMra022361 12904523.

31. Wang LT, Ting CH, Yen ML, Liu KJ, Sytwu HK, Wu KK, et al. Human mesenchymal stem cells (MSCs) for treatment towards immune- and inflammation-mediated diseases: review of current clinical trials. J Biomed Sci. 2016;23(1):76. doi: 10.1186/s12929-016-0289-5 27809910.

32. Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol. 2008;8(9):726–36. doi: 10.1038/nri2395 19172693.

33. Wang L, Zhao Y, Shi S. Interplay between Mesenchymal Stem Cells and Lymphocytes: Implications for Immunotherapy and Tissue Regeneration. J Dent Res. 2012;91(11):1003–10. doi: 10.1177/0022034512460404 22988011

34. Duffy MM, Ritter T, Ceredig R, Griffin MD. Mesenchymal stem cell effects on T-cell effector pathways. Stem Cell Res Ther. 2011;2(4):34. doi: 10.1186/scrt75 21861858.

35. Li M, Sun X, Kuang X, Liao Y, Li H, Luo D. Mesenchymal stem cells suppress CD8+ T cell-mediated activation by suppressing natural killer group 2, member D protein receptor expression and secretion of prostaglandin E2, indoleamine 2, 3-dioxygenase and transforming growth factor-beta. Clin Exp Immunol. 2014;178(3):516–24. doi: 10.1111/cei.12423 25070361.

36. Chen PM, Yen ML, Liu KJ, Sytwu HK, Yen BL. Immunomodulatory properties of human adult and fetal multipotent mesenchymal stem cells. J Biomed Sci. 2011;18:49. doi: 10.1186/1423-0127-18-49 21762539.

37. Corcione A, Benvenuto F, Ferretti E, Giunti D, Cappiello V, Cazzanti F, et al. Human mesenchymal stem cells modulate B-cell functions. Blood. 2006;107(1):367–72. doi: 10.1182/blood-2005-07-2657 16141348.

38. Jiang XX, Zhang Y, Liu B, Zhang SX, Wu Y, Yu XD, et al. Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood. 2005;105(10):4120–6. doi: 10.1182/blood-2004-02-0586 15692068.

39. Cassatella MA, Mosna F, Micheletti A, Lisi V, Tamassia N, Cont C, et al. Toll-like receptor-3-activated human mesenchymal stromal cells significantly prolong the survival and function of neutrophils. Stem Cells. 2011;29(6):1001–11. doi: 10.1002/stem.651 21563279.

40. Kim N, Cho SG. New strategies for overcoming limitations of mesenchymal stem cell-based immune modulation. Int J Stem Cells. 2015;8(1):54–68. doi: 10.15283/ijsc.2015.8.1.54 26019755.

41. Harding J, Roberts RM, Mirochnitchenko O. Large animal models for stem cell therapy. Stem Cell Res Ther. 2013;4(2):23. doi: 10.1186/scrt171 23672797.

42. Sheng CC, Zhou L, Hao J. Current stem cell delivery methods for myocardial repair. Biomed Res Int. 2013;2013:547902. doi: 10.1155/2013/547902 23509740.

43. Kurtz A. Mesenchymal stem cell delivery routes and fate. Int J Stem Cells. 2008;1(1):1–7. doi: 10.15283/ijsc.2008.1.1.1 24855503.


Článek vyšel v časopise

PLOS One


2019 Číslo 12
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

KOST
Koncepce osteologické péče pro gynekology a praktické lékaře
nový kurz
Autoři: MUDr. František Šenk

Sekvenční léčba schizofrenie
Autoři: MUDr. Jana Hořínková

Hypertenze a hypercholesterolémie – synergický efekt léčby
Autoři: prof. MUDr. Hana Rosolová, DrSc.

Svět praktické medicíny 5/2023 (znalostní test z časopisu)

Imunopatologie? … a co my s tím???
Autoři: doc. MUDr. Helena Lahoda Brodská, Ph.D.

Všechny kurzy
Kurzy Podcasty Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

#ADS_BOTTOM_SCRIPTS#