The revolutionary role of placental derivatives in biomedical research

Abstract

The human placenta is a transient yet crucial organ that plays a key role in sustaining the relationship between the maternal and fetal organisms. Despite its historical classification as "biowaste," placental tissues have garnered increasing attention since the early 1900s for their significant medical potential, particularly in wound repair and surgical application. As ethical considerations regarding human placental derivatives have largely been assuaged in many countries, they have gained significant attention due to their versatile applications in various biomedical fields, such as biomedical engineering, regenerative medicine, and pharmacology. Moreover, there is a substantial trend toward various animal product substitutions in laboratory research with human placental derivatives, reflecting a broader commitment to advancing ethical and sustainable research methodologies. This review provides a comprehensive examination of the current applications of human placental derivatives, explores the mechanisms behind their therapeutic effects, and outlines the future potential and directions of this rapidly advancing field.

Keywords: Biomedical research; Decellularization; Extracellular matrix; Extracellular vesicle; Placenta; Regenerative medicine; Stem cells.

Graphical abstract

Fig. 1

The early development and structure of the placenta. Placenta early development (a), After the blastocyst implantation, the placental development starts with the invasion of syncytiotrophoblast cells into the maternal uterine tissue. This invasion leads to the formation of chorionic villi, which are subsequently covered by CTCs to create the protective outer shell of the placenta, (b) the illustration of the layers of the placental membrane, and (c) the mature placenta structure, which exhibits both fetal and maternal blood circulation.

Fig. 2

Schematic representation of placenta-derived stem cells and potential applications. The sources of placenta-derived stem cells, various isolation techniques, and potential therapeutic applications. Abbreviations: Amniotic epithelial cells, AECs; Cord lining epithelial cell, CLEC; Endothelial progenitor cell, EPC; Mesenchymal stem cells, MSCs; Hematopoietic stem cell, HSC; Trophoblastic cells, TCs.

Fig. 3

Application of placental CM. CM derived from placental MSCs has shown significant therapeutic potential across diverse diseases, including fibrotic disorders, cardiovascular diseases, cancers, as well as conditions related to gynecology and obstetrics. Meanwhile, studies demonstrated that CM from TBs altered HSCs transcriptome and promoted osteogenic differentiation. Furthermore, CM from AECs induced angiogenesis and tube formation in the ovary. Abbreviations: acute myocardial infarction, AMI; amniotic epithelial cells, AECs; Conditioned medium, CM; hematopoietic stem cells, HSCs; mesenchymal stem cells, MSCs; trophoblasts, TBs; premature ovarian failure, POF.

Fig. 4

Placental extract properties. The properties of placental extract encompass potent antioxidant and anti-inflammatory activities, regulation of cell fate, immunomodulation, tissue regeneration promotion, and hormone-like effects.

Fig. 5

Illustration of different placenta decellularization techniques and the applications of decellularized tissue in regenerative medicine. Placenta decellularization techniques include physical, chemical, enzymatic, or their combinations. Depending on its recellularization status, a decellularized placenta can be tailored for various regenerative medicine applications.

Fig. 6

Illustration of the formation of EVs through the endocytic pathway in placental cells. Endosomes are formed through the inward folding of the plasma membrane. MVBs are generated when these endosomes undergo invaginations of their membrane, leading to the ILVs formation inside. EVs are produced when these ILVs are released from the cells. Abbreviations: Extracellular vehicles, EVs; Intraluminal vesicles, ILVs; Multivesicular bodies, MVBs.

Fig. 7

Sampling, isolation, components, and applications of AF derivatives. Comprehensive overview of AF derivatives, including the processes of sampling and isolation, characterization of key components, and their diverse therapeutic and biomedical applications. Abbreviation: Amniotic fluid, AF.