Poster, Podium & Video Sessions
Presentation Authors: Aram Kim*, Hwan Yeul Yu, Jisun Lim, Ju Young Han, Chae-Min Ryu, Jun Ki Kim, Hyung-Min Chung, Dong-Myung Shin, Myung-Soo Choo, Seoul, Korea, Republic of
Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) and ketamine induced cystitis (KC) are uncontrolled diseases which are characterized by severe pelvic pain and urinary frequency. Here, we show superior therapeutic efficacy of multipotent stem-cells (M-MSC) derived from human embryonic stem-cells (hESC) and long-term in vivo tracing of them.
Methods: We used three kinds of IC/BPS and KC rat model in order to show all major pathophysiology of IC/BPS and KC.
The therapeutic effect of M-MSCs was examined by awake cystometry, immunohistochemistry staining (H&E, Toluidine blue, Masson’s trichrome, TUNEL) after 1 week of MSCs injection. Additionally, we examined the expression of genes related to inflammation, mast cell infiltration and apoptosis by performing RQ-PCR analysis to show therapeutic effect underlying the benefits of M-MSC therapy after 1 week of transplantation.To confirm tumorigenesis or immune mediated transplant rejection of MSC, we performed micro-PET and autopsy after 1 year of transplantation of M-MSC. Furthermore we investigated mechanism of MSC therapy using longitudinal monitoring of infused M-MSCs using confocal micro-endoscopy and microscopy in living rat model after 6 months of transplantation of M-MSCs.
Results: A single local transplantation of M-MSCs was effective to treat the IC and KC bladders as evidenced by ameliorated bladder voiding function and characteristic pathological features. In particularly, the therapeutic potency of M-MSCs was superior to that based on human umbilical cord blood-MSCs, reducing a required cell number up to 10 folds. Any adverse outcome regarding abnormal growth was not observed in either animal during 1 year investigation by micro-PET and autopsy. Longitudinal monitoring of infused M-MSCs using confocal micro-endoscopy and microscopy in living rat model demonstrated that living green florescent protein tagged cells keep alive and integrated as urothelium layer as well as vascular structure after 6 months of transplantation of M-MSCs.
Conclusions: This study provides the first evidence of the superior therapeutic efficacy, long-term safety, in vivo graft survival, and possible therapeutic mechanism of hESC-derived M-MSCs in preclinical studies.
Source Of Funding: none