Sub-Regional Differences of the Human Amniotic Membrane and Their Potential Impact on Tissue Regeneration Application

Abstract

For more than 100 years, the human amniotic membrane (hAM) has been used in multiple tissue regeneration applications. The hAM consists of cells with stem cell characteristics and a rich layer of extracellular matrix. Undoubtedly, the hAM with viable cells has remarkable properties such as the differentiation potential into all three germ layers, immuno-modulatory, and anti-fibrotic properties. At first sight, the hAM seems to be one structural entity. However, by integrating its anatomical location, the hAM can be divided into placental, reflected, and umbilical amniotic membrane. Recent studies show that cells of these amniotic sub-regions differ considerably in their properties such as morphology, structure, and content/release of certain bioactive factors. The aim of this review is to summarize these findings and discuss the relevance of these different properties for tissue regeneration. In summary, reflected amnion seems to be more immuno-modulatory and could have a higher reprogramming efficiency, whereas placental amnion seems to be pro-inflammatory, pro-angiogenic, with higher proliferation and differentiation capacity (e.g., chondrogenic and osteogenic), and could be more suitable for certain graft constructions. Therefore, we suggest that the respective hAM sub-region should be selected in consideration of its desired outcome. This will help to optimize and fine-tune the clinical application of the hAM.

NADPH Oxidases: Redox Regulators of Stem Cell Fate and Function

“…The human amniotic membrane (hAM) consists of an epithelial layer, formed by a monolayer of human amniotic epithelial cells (hAECs), and a collagen-rich mesenchymal layer, in which the human amniotic mesenchymal stromal cells (hAMSCs) are embedded [ 72 ]. Cells of the hAM can differentiate into cells of all three germ layers in vitro and in vivo [ 73 ]. Perinatal stem cells in general possess embryonic stem cell-like differentiation capability and adult stem cell-like immunomodulatory properties [ 74 ].…”

Systematic Review of the Application of Perinatal Derivatives in Animal Models on Cutaneous Wound Healing

“…As the most commonly used perinatal tissue is the hAM, we assume that the poor percentage of the in vitro characterization is due to the fact that the hAM has been characterized and tested many times before. Further, identification and preparation of the hAM are unambiguous and straightforward (Jerman et al, 2014;Poženel et al, 2019;Jerman et al, 2020;Ramuta et al, 2020;Weidinger et al, 2020), whereas cells and cell-derived secretomes or sEV require precise characterization. Since the vast majority of the researchers isolated cells from the perinatal tissues by themselves, adequate characterization is mandatory to assure that a pure cell population has been isolated.…”

The Role of Innate Immune System in the Human Amniotic Membrane and Human Amniotic Fluid in Protection Against Intra-Amniotic Infections and Inflammation

“…At term a subpopulation of hAEC expresses embryonic stem cell surface markers, such as tumor rejection antigens 1-60 (TRA1-60) and TRA1-81 ( 11 – 13 ), stage-specific embryonic antigens 3 and 4 (SSEA-3, SSEA-4) ( 11 , 13 , 14 ), and also some transcription factors characteristic for stem cells, such as OCT-4, NANOG, SOX-2 and SOX-3 ( 11 , 12 , 15 , 16 ). Similarly, a subpopulation of hAMSC also expresses some of the pluripotency markers, namely TRA-1-61, TRA1-81 ( 17 ), OCT-3 ( 18 ), OCT-4 ( 17 – 19 ), SSEA-3, SSEA-4 ( 17 , 20 ), SOX-2 and NANOG ( 19 , 20 ). Moreover, hAEC and hAMSC are capable of differentiation into all three germ layers, namely ectoderm, mesoderm and endoderm ( 15 , 17 , 21 ).…”