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Incorporation of Smooth Muscle Cells Derived from Human Adipose Stem Cells on Poly(Lactic-co-Glycolic Acid) Scaffold for the Reconstruction of Subtotally Resected Urinary Bladder in Athymic Rats

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

The urinary tract can be affected by both congenital abnormalities as well as acquired disorders, such as cancer, trauma, infection, inflammation, and iatrogenic injuries, all of which may lead to organ damage requiring eventual reconstruction. As a gold standard, gastrointestinal segment is used for urinary bladder reconstruction. However, one major problem is that while bladder tissue prevents reabsorption of specific solutes, gastrointestinal tissue actually absorbs them. Therefore, tissue engineering approach had been attempted to provide an alternative tissue graft for urinary bladder reconstruction.

Methods:

Human adipose-derived stem cells isolated from fat tissues were differentiated into smooth muscle cells and then seeded onto a triple-layered PLGA sheet to form a bladder construct. Adult athymic rats underwent subtotal urinary bladder resection and were divided into three treatment groups (n = 3): Group 1 (“sham”) underwent anastomosis of the remaining basal region, Group 2 underwent reconstruction with the cell-free scaffold, and Group 3 underwent reconstruction with the tissue-engineered bladder construct. Animals were monitored on a daily basis and euthanisation was performed whenever a decline in animal health was detected.

Results:

All animals in Groups 1, 2 and 3 survived for at least 7 days and were followed up to a maximum of 12 weeks post-operation. It was found that by Day 14, substantial ingrowth of smooth muscle and urothelial cells had occurred in Group 2 and 3. In the long-term follow up of group 3 (tissue-engineered bladder construct group), it was found that the urinary bladder wall was completely regenerated and bladder function was fully restored. Urodynamic and radiological evaluations of the reconstructed bladder showed a return to normal bladder volume and function.Histological analysis revealed the presence of three muscular layers and a urothelium similar to that of a normal bladder. Immunohistochemical staining using human-specific myocyte markers (myosin heavy chain and smoothelin) confirmed the incorporation of the seeded cells in the newly regenerated muscular layers.

Conclusion:

Implantation of PLGA construct seeded with smooth muscle cells derived from human adipose stem cells can lead to regeneration of the muscular layers and urothelial ingrowth, leading to formation of a completely functional urinary bladder.

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Acknowledgements

The study was funded by Universiti Kebangsaan Malaysia Medical Centre Grants: GUP-2017-092, FF-173-2010 and Young Researcher Grant: GGPM-2011-079.

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Authors and Affiliations

  1. Urology Unit, Department of Surgery, UKM Medical Centre, Kuala Lumpur, Malaysia

    Salah Abood Salem, Mohd Hafidzul Jasman, Ismail Sagap & Zulkifli Md. Zainuddin

  2. Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000, Kuala Lumpur, Malaysia

    Salah Abood Salem, Zahra Rashidbenam, Ruszymah Bt Haji Idrus & Min Hwei Ng

  3. School of Medicine, Taylor`s University, Subang Jaya, Selangor Darul Ehsan, Malaysia

    Christopher Chee Kong Ho

  4. Department of Orthopaedics and Traumatology, UKM Medical Centre, Kuala Lumpur, Malaysia

    Rajesh Singh

  5. Material Technology Group, Malaysian Nuclear Agency, Kajang, Selangor Darul Ehsan, Malaysia

    Mohd Reusmaazran Yusof

  6. Department of Physiology, UKM Medical Faculty, Kuala Lumpur, Malaysia

    Ruszymah Bt Haji Idrus

Authors
  1. Salah Abood Salem
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  2. Zahra Rashidbenam
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  8. Zulkifli Md. Zainuddin
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Correspondence to Min Hwei Ng.

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The authors declare that there are no financial conflicts of interest regarding the publication of this paper.

Ethical statement

Human samples used in this study were obtained and processed with informed consent from patients undergoing abdominoplasty according to procedures approved by the Institutional Research and Ethics Committee (Approval code: FF-173-2010). Experimentation on rats in this study followed guidelines and procedures approved by the Institutional Animal Ethics Committee (Approval code: PP/SURG/2010/ZULKIFLI/17-MARCH/292-MARCH-2010 DECEMBER-2011).

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Salem, S.A., Rashidbenam, Z., Jasman, M.H. et al. Incorporation of Smooth Muscle Cells Derived from Human Adipose Stem Cells on Poly(Lactic-co-Glycolic Acid) Scaffold for the Reconstruction of Subtotally Resected Urinary Bladder in Athymic Rats. Tissue Eng Regen Med 17, 553–563 (2020). https://doi.org/10.1007/s13770-020-00271-7

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