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: 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


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