간질성 방광염 / 방광 통증 증후군을 타겟으로 하는 줄기세포 치료를 위한 생체 내 분포 및 이식 된 세포의 특성 모니터링

Abstract

Mesenchymal stem cells (MSC) have been considered as a novel therapeutic approach for interstitial cystitis/bladder pain syndrome (IC/BPS), which is an intractable disease characterized by severe pelvic pain and urinary frequency. However, little direct analysis of in vivo properties of the transplanted cells hampers the precise understanding of their underlying therapeutic mechanisms after transplantation and developing optimal transplantation protocols. Here, we showed the in vivo distribution and perivascular integration of human embryonic stem-cell (hESC) derived multipotent stem-cell (M-MSC) in living animals and their improved therapeutic outcomes in a lipopolysaccharide (LPS) instillation-induced IC/BPS animal model. A novel combination of longitudinal intravital confocal fluorescence imaging and microcystoscopy in living animals with concomitant immunofluorescent staining of bladder tissues demonstrated that infused M-MSCs initially engrafted as multiple types of cells and gradually integrated as perivascular-like structure until 30 days after transplantation. Long-term engraftment ensured the efficient and long-lasting therapeutic effects of M-MSCs in ameliorating the defective bladder voiding function and repairing the pathological characteristics of IC/BPS bladder. Thus, present study longitudinally monitors in vivo properties of the long-term grafted hESC derived M-MSCs in living animals as well as demonstrates their improved efficacy for treating IC/BPS.