Smooth Muscle Progenitor Cells Derived From Human Pluripotent Stem Cells Induce Histologic Changes in Injured...

Area of Science:

• Regenerative Medicine
• Stem Cell Biology
• Urology

Background:

• Limited knowledge exists on the in vivo effects of human stem cells on injured muscles.
• Myoblasts from various sources can restore muscle function, primarily through paracrine effects rather than direct regeneration.

Purpose of the Study:

• To investigate the in vivo integration and effects of smooth muscle progenitor cells (pSMCs) derived from human pluripotent stem cells (hPSCs).
• To evaluate the potential of hPSC-derived pSMCs in restoring urethral sphincter function and regenerating injured urethral tissue.

Main Methods:

• pSMCs were derived from human embryonic stem cells (H9-ESCs) and induced pluripotent stem cells (iPSCs).
• pSMCs were injected into rat urethral injury models and immunodeficient mice.
• Histologic analysis, Western blot, immunofluorescence staining, and in vivo bioluminescence imaging were used to assess cell engraftment, tissue regeneration, and functional restoration.

Main Results:

• pSMC treatment led to increased elastic fibers and thicker muscle layers in rat urethras.
• Elevated elastin and collagen III content was observed in the treated urethras and bladders.
• Engraftment and smooth muscle phenotype persistence of pSMCs were confirmed in host tissues, with no detectable human elastin gene expression in rodent tissues.
• Evidence suggests native tissue remodeling induced by pSMCs, alongside direct smooth muscle cell regeneration.

Conclusions:

• hPSC-derived pSMCs restore urethral sphincter function through direct smooth muscle cell regeneration and by inducing native tissue remodeling.
• These findings support the use of hPSC-derived pSMCs for regenerative therapies in lower urinary tract conditions.
• The study highlights the dual mechanism of action for pSMCs in tissue repair and functional restoration.