Human Amniotic Membrane and Amniotic Membrane-Derived Cells: How Far Are We from Their Use in Regenerative and Reconstructive Urology?

Abstract

Human amniotic membrane (hAM) is the innermost layer of fetal membranes, which surrounds the developing fetus and forms the amniotic cavity. hAM and hAM-derived cells possess many properties that make them suitable for use in regenerative medicine, such as low immunogenicity, promotion of epithelization, anti-inflammatory properties, angiogenic and antiangiogenic properties, antifibrotic properties, antimicrobial properties, and anticancer properties. Many pathological conditions of the urinary tract lead to organ damage or complete loss of function. Consequently, the reconstruction or replacement of damaged organs is needed, which makes searching for new approaches in regenerative and reconstructive urology a necessity. The use of hAM for treating defects in kidneys, ureters, urinary bladder, and urethra was tested in vitro in cell cultures and in vivo in mice, rats, rabbits, cats, dogs, and also in humans. These studies confirmed the advantages and the potential of hAM for use in regenerative and reconstructive urology as stated above. However, they also pointed out a few concerns we have to take into consideration. These are (1) the lack of a standardized protocol in hAM preparation and storage, (2) the heterogeneity of hAM, and especially (3) low mechanical strength of hAM. Before any wider use of hAM for treating urological defects, the protocols for preparation and storage will need to be standardized, followed by more studies on larger animals and clinical trials, which will altogether extensively assess the potential of hAM use in urological patients.

Keywords: human amniotic membrane; regenerative medicine; stem cells; tissue engineering; urology; urothelium.

Figure 1.

Structure of human amniotic membrane (hAM). hAM consists of human amniotic epithelial cells (hAECs), basal lamina, and hAM stroma contains human amniotic mesenchymal stromal cells (hAMSCs) and is divided into 3 layers: the compact layer, the hAMSC layer, and the spongy layer.

Figure 2.

Scheme of the urinary tract: (A) kidney, (B) ureter, (C) urinary bladder, and (D) urethra. Urothelium covers the inner surface of the renal pelvis, ureters, urinary bladder, and the proximal part of the urethra, while the distal part of the urethra is covered with stratified columnar epithelium.

Figure 3.

Different scaffolds of human amniotic membrane (hAM). (A) hAM: The scaffold consists of human amniotic epithelial cells (hAEC), basal lamina, and hAM stroma. (B) dAM (denuded hAM): hAECs were removed from hAM before the application. (C) sAM (stroma hAM): hAM is oriented with hAM stroma facing the site of the application. (D) Folded hAM: hAM was folded in half with hAECs facing outside. (E) Multilayered hAM: Four hAM were stacked into multilayered hAM and dried. (F) hAM + PLCL: The sandwich-structured biocomposite, constructed from hAM, covered from both sides with a 2-layered poly(l-lactide-co-ε-caprolactone) (PLCL) membrane. (G) Cell-seeded dAM: hAECs were removed from hAM and then cells were seeded on the dAM.

Figure 4.

Histology of the urinary bladder. (A) Porcine urinary bladder, which is histologically similar to normal human urothelium. The analysis of porcine urinary bladder was approved by the Veterinary Administration of the Slovenian Ministry of Agriculture and Forestry in compliance with the Animal Health Protection Act and the Instructions for Granting Permits for Animal Experimentation for Scientific Purposes. Urothelium is marked with a dotted square. Scale bar 100 µm. (B) The scheme of the urothelium: Urothelium is composed of superficial (umbrella), intermediate, and basal urothelial cells.