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Predifferentiated Smooth Muscle-Like Adipose-Derived Stem Cells for Bladder Engineering.

Jakub Smolar1, Maya Horst2, Souzan Salemi1

  • 1Department of Urology, University Hospital Zurich, Zurich, Switzerland.

Tissue Engineering. Part A
|February 26, 2020
PubMed
Summary

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Predifferentiated adipose-derived stem cells (pADSCs) combined with smooth muscle cells (SMCs) in a 1:1 ratio enhance smooth muscle tissue regeneration. This combination improves organoid formation, contractility, and extracellular matrix remodeling for bladder tissue engineering.

Area of Science:

  • Regenerative Medicine
  • Tissue Engineering
  • Stem Cell Biology

Background:

  • Organs comprise diverse cell types interacting within a microenvironment for tissue homeostasis and function.
  • Developing functional smooth muscle tissue requires simulating a multicellular microenvironment.
  • Multilineage adipose-derived stem cells (ADSCs) offer a potential cell source for smooth muscle cell (SMC) replacement in detrusor bioengineering.

Purpose of the Study:

  • To investigate if predifferentiated smooth muscle-like ADSCs (pADSCs) support SMCs in generating stable smooth muscle tissue.
  • To analyze extracellular matrix (ECM) remodeling and factor secretion in SMC-pADSC co-cultures.
  • To evaluate the potential of pADSCs as an alternative to SMCs in bladder tissue engineering.

Main Methods:

Keywords:
bladder smooth musclecocultureproteomeregenerative medicinestem cell

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  • Rat SMCs and pADSCs were mono- and co-cultured at ratios of 1:1, 1:2, 1:3, and 1:5 for up to 2 weeks.
  • Assessed SMC-specific markers (alpha-smooth muscle actin, calponin, MyH11, smoothelin), cell proliferation, and contractility.
  • Performed proteomic analysis of secretome and cell pellets, focusing on ECM deposition, remodeling, integrin expression, and growth factor secretion.

    • Main Results:

    • SMC and pADSC co-cultures, particularly at a 1:1 ratio, showed significantly increased smooth muscle organoid formation and improved contractility.
    • Organoids exhibited a structured arrangement: an SMC core surrounded by a pADSC layer.
    • Increased deposition of ECM proteins (collagens, fibrillin 1) and altered secretion of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) were observed in contact co-cultures.

    Conclusions:

    • SMC-pADSC 1:1 co-cultures demonstrated enhanced cell proliferation, contractility, and organoid formation compared to monocultures and other ratios.
    • The 1:1 co-culture maintained a stable SMC phenotype, mediated by increased ECM deposition and remodeling.
    • Autologous pADSCs hold promise for substituting SMCs in generating contractile detrusor muscle tissue for bladder tissue engineering applications.