MSC-based therapy in female pelvic floor disorders

Abstract

Mesenchymal stem cells (MSCs), also referred to as multipotent stromal cells or mesenchymal stromal cells, are present in multiple tissues and capable of differentiating into diverse cell lineages, holding a great promise in developing cell-based therapy for a wide range of conditions. Pelvic floor disorders (PFDs) is a common degenerative disease in women and may diminish a woman's quality of life at any age. Since the treatments for this disease are limited by the high rates of recurrence and surgical complications, seeking an ideal therapy in the restoration of pelvic floor function is an urgent issue at present. Herein, we summarize the cell sources of MSCs used for PFDs and discuss the potential mechanisms of MSCs in treating PFDs. Specifically, we also provide a comprehensive review of current preclinical and clinical trials dedicated to investigating MSC-based therapy for PFDs. The novel therapy has presented promising therapeutic effects which include relieving the symptoms of urinary or fecal incontinence, improving the biological properties of implanted meshes and promoting the injured tissue repair. Nevertheless, MSC-based therapies for PFDs are still experimental and the unstated issues on their safety and efficacy should be carefully addressed before their clinical applications.

Keywords: Cell- and tissue-based therapy; Mesenchymal stem cells; Mesenchymal stem cells transplantation; Pelvic floor disorders.

Fig. 1

Schematic representation of the different MSCs sources and MSC-based therapies for PFDs

Fig. 2

Simplified representation of the potential roles of MSCs in treating PFDs. FBR foreign body response

Fig. 3

BLI of hMSC localization in VD rats: a Representative longitudinal BLI images from a VD rat showing increasing BLI signal on days 1 and 2 following periurethral injection of luciferase-expressing hMSCs. b Mean BLI signal in VD animals significantly increased on days 1 and 2 (P < 0.05) in comparison with day 0, suggestive of hMSC recruitment/viability. No significant difference was observed for non-VD rats. c Representative urethra 2 h after hMSC injection demonstrates hMSCs: human-specific Alu repeats clearly revealed nuclear staining of hMSCs, whereas no positive Alu signal was found in urethra of imaged animals when BLI signal disappeared. Light microscopy ×40. BLI bioluminescence imaging, hMSC human mesenchymal stem cells, VD vaginal distention. Reprinted with permissions from Sadeghi et al. [80]

Fig. 4

eMSC transduction and survival of eMSC on PA + G mesh in NSG mice. a cultured mCherry transduced eMSC showing red fluorescence, b more than 95% of transduced and cultured eMSC were mCherry + by flow cytometry and about 40% of this population were SUSD2+. Representative trace of n = 6 patient samples, c PA + G mesh seeded and cultured with eMSC. d, e mCherry + eMSC were observed 3 and f, g 7 days post-implantation around the mesh filaments in immunocompromised NSG mice. Arrows, representative mCherry + eMSC; m, mesh filament; g, gelatin. Scale Bars 100 µm. Reprinted with permissions from Darzi et al. [86]

Fig. 5

Subject disposition. AMDC-USR autologous muscle derived cells for urinary sphincter repair; n number of subjects. Reprinted with permissions from Ron J. Jankowski et al. (2018)