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. 2022 Oct;5(5):453-460.
doi: 10.1002/ame2.12280. Epub 2022 Oct 8.

Human primary muscle stem cells regenerate injured urethral sphincter in athymic rats

Biniam M Bekele  1   2   3   4 , Verena Schöwel-Wolf  1   2   3   4 , Janine Kieshauer  1   2   3 , Andreas Marg  1   2   3 , Andreas Busjahn  5 , Sarah Davis  6 , Gayle Nugent  6 , Anne-Karoline Ebert  7 , Simone Spuler  1   2   3   4
Affiliations

Human primary muscle stem cells regenerate injured urethral sphincter in athymic rats

Biniam M Bekele et al. Animal Model Exp Med. 2022 Oct.

Abstract

Background: The aim of the study was to demonstrate the efficacy of human muscle stem cells (MuSCs) isolated using innovative technology in restoring internal urinary sphincter function in a preclinical animal model.

Methods: Colonies of pure human MuSCs were obtained from muscle biopsy specimens. Athymic rats were subjected to internal urethral sphincter damage by electrocauterization. Five days after injury, 2 × 105 muscle stem cells or medium as control were injected into the area of sphincter damage (n = 5 in each group). Peak bladder pressure and rise in pressure were chosen as outcome measures. To repeatedly obtain the necessary pressure values, telemetry sensors had been implanted into the rat bladders 10 days prior to injury.

Results: There was a highly significant improvement in the ability to build up peak pressure as well as a pressure rise in animals that had received muscle stem cells as compared to control (p = 0.007) 3 weeks after the cells had been injected. Only minimal histologic evidence of scarring was observed in treated rats.

Conclusion: Primary human muscle stem cells obtained using innovative technology functionally restore internal urethral sphincter function after injury. Translation into use in clinical settings is foreseeable.

Keywords: human muscle stem cells; sphincter injury; telemetry; urinary incontinence; urodynamics.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Experimental design. DSI was surgically implanted (D0) followed by the first urodynamic measurement (pre‐injury, D7). On day 10 (D10) the urethral sphincter was injured using electrocauterization followed on day 15 (D15) by the injection of either MuSCs or placebo into the urethral sphincter. The second urodynamic measurement (post‐injection) was done on day 37 (D37)
FIGURE 2
FIGURE 2
Graphic description of telemetry parameters. BaseP, base pressure; ICI, inter‐contraction interval; PeakD, peak duration; PeakP, peak pressure
FIGURE 3
FIGURE 3
A full 24‐h monitoring trace of conscious rats using bladder telemetry. These traces were recorded pre‐injury. Animals were kept in a 12‐h light/dark cycle. The first 12 h represent the light hours
FIGURE 4
FIGURE 4
Representative post‐injection bladder pressure tracings during 24 h of measurement. Pressure is measured in mmHg and corresponding time of the day is indicated in the x‐axis
FIGURE 5
FIGURE 5
Change in urodynamic parameters between pre‐injury and post‐injection. Each point represents the 24 h median value of each animal. Control n = 3, verum n = 4. BaseP, base pressure; PeakP, peak pressure; Rise, difference between PeakP and BaseP
FIGURE 6
FIGURE 6
Histologic findings in urethral sphincter post‐injection. (A), Hematoxylin & Eosin staining showing injury related tissue changes in the placebo group (*, scarring; +, degenerative changes) (B), Hematoxylin & Eosin staining showing normal urethral sphincter tissue architecture in the verum group
See this image and copyright information in PMC

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