The application of decellularized human term fetal membranes in tissue engineering and regenerative medicine (TERM)

doi:10.1016/j.placenta.2017.07.002

Placenta

Volume 59, November 2017, Pages 124-130

https://doi.org/10.1016/j.placenta.2017.07.002 Get rights and content

Highlights

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Fetal membranes are a valuable source of ECM-based biomaterial to expand and promote maturation of stem cells from different sources.
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Decellularized fetal membranes can be processed into two/three dimensional scaffolds and cell/drug delivery particles to promote regeneration.
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Decellularized fetal membranes can be used as a novel approach for cancer therapies.
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Decellularized fetal membranes provide a platform to better understand the role of extracellular matrix in stem cell function.

Abstract

Tissue engineering and regenerative medicine (TERM) is a field that applies biology and engineering principles to “restore, maintain or repair a tissue after injury”. Besides the potential to treat various diseases, these endeavours increase our understanding of fundamental cell biology. Although TERM has progressed rapidly, engineering a whole organ is still beyond our skills, primarily due to the complexity of tissues. Material science and current manufacturing methods are not capable of mimicking this complexity. Therefore, many researchers explore the use of naturally derived materials that maintain important biochemical, structural and mechanical properties of tissues. Consequently, employing non-cellular components of tissues, particularly the extracellular matrix, has emerged as an alternative to synthetic materials. Because of their complexity, decellularized tissues are not as well defined as synthetic materials but they provide cells with a microenvironment that resembles their natural niche.

Decellularized tissues are produced from a variety of sources, among which the fetal membranes are excellent candidates since their supply is virtually unlimited, they are readily accessible with minimum ethical concerns and are often discarded as a biological waste. In this review, we will discuss various applications of decellularized fetal membranes as substrates for the expansion of stem cells, their use as two and three-dimensional scaffolds for tissue regeneration, and their use as cell delivery systems. We conclude that fetal membranes have great potential for use in TERM.

Section snippets

Fetal membranes

The human fetal membranes envelop the fetus and amniotic fluid to form a sac, which acts as an interface with the mother and protects the fetus during pregnancy [1], [2]. In the following sections, we summarize important aspects of the structure and properties of human fetal membranes, the various stem cell populations harboured in human fetal membranes, and briefly describe the history of use of fetal membranes as biomaterials.

Decellularization: exposing the extracellular matrix (ECM)

ECM surrounds all adherent cells in body; which is a complex network of different soluble and non-soluble biomolecules including proteins, glycoproteins and glycosaminoglycans (GAGs). Historically, the role of the ECM was perceived to be an anchor for cell attachment and for defining tissue shape, but there is increasing evidence that ECM regulates cell behaviours [31], [32]. ECM contributes to cellular functions through compositional, structural/organisational and mechanical properties [32],

Growth surfaces to enhance stem cell properties

Decellularized fetal membranes affect the differentiation potential and maturation of MSCs. MSCs grown on decellularized fetal membrane surfaces show greater potential for osteogenesis and adipogenesis depending on which side of the decellularized fetal membranes they are grow when compared with MSCs grown on tissue culture plastic (TCP). The stromal side of decellularized AM (dAM) stimulates differentiation into hard tissues such as bone, whereas the epithelial side of dAM is more efficient in

Conclusion

Decellularized fetal membranes show promise as surfaces to expand and promote maturation of stem cells from different sources, as 2D/3D scaffolds to improve regeneration and as cell/drug delivery particles. Despite the progress in manufacturing various structures from dAM, the applications of fetal membranes in tissue engineering are in their infancy and more research is needed to fully explore their potential. Attempts to solubilize fetal membranes will allow the production of more uniform

Acknowledgment

The authors want to acknowledge that parts of Fig. 1 were adapted from the artwork by Maurizio Fusillo from The Noun Project under the Creative Commons Corporation licence (https://creativecommons.org/licenses/by/3.0/legalcode). We would like to acknowledge the Selby Foundation, Equity Trustees, the Hallmark Therapeutic Technologies Research Initiative, and the Particulate Fluids Processing Centre for support.

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Citation Excerpt :
ECM hydrogels may be used in the future as part of the treatment of Asherman's syndrome and endometrial atrophy (Table 1). The amnion membrane (AM), a prospective biomaterial, can not only act as a mechanical barrier that separates the wounded surface but also secrete various growth factors to activate the regulation of endometrial cell proliferation, migration, and differentiation, thereby achieving morphological and functional recovery of the uterus [79,80]. In the clinical setting, both the fresh and lyophilized AM have been used for IUA therapy [81,82].
Intrauterine adhesions (IUAs) refer to the repair disorder after endometrial injury and may lead to uterine infertility, recurrent miscarriage, abnormal menstrual bleeding, and other obstetric complications. It is a pressing public health issue among women of childbearing age. Presently, there are limited clinical treatments for IUA, and there is no sufficient evidence that these treatment modalities can effectively promote regeneration after severe endometrial injury or improve pregnancy outcome. The inhibitory pathological micro-environment is the main factor hindering the repair of endometrial damaged tissues. To address this, tissue engineering and regenerative medicine have been achieving promising developments. Particularly, biomaterials have been used to load stem cells or therapeutic factors or construct an in situ delivery system as a treatment strategy for endometrial injury repair. This article comprehensively discusses the characteristics of various bio-scaffold materials and their application as stem cell or therapeutic factor delivery systems constructed for uterine tissue regeneration.
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The application of decellularized human term fetal membranes in tissue engineering and regenerative medicine (TERM)

Highlights

Abstract

Section snippets

Fetal membranes

Decellularization: exposing the extracellular matrix (ECM)

Growth surfaces to enhance stem cell properties

Conclusion

Acknowledgment

Biomaterials

Placenta

Placenta

Int. Immunopharm.

Acta Biomater.

Biomaterials

Stem Cell Res. Ther.

Surv. Ophthalmol.

Biomaterials

Transl. Res.

Methods

Biomaterials

Biomaterials

Biomaterials

Placenta

Placenta as a source of stem cells for regenerative medicine

Curr. Pathobiol. Rep.

Production of an acellular amniotic membrane matrix for use in tissue engineering

Tissue Eng.

The foetal membranes: a review of the anatomy of normal amnion and chorion and some aspects of their function

Postgrad. Med. J.

Concise review: isolation and characterization of cells from human term placenta: outcome of the first international workshop on placenta derived stem cells

Stem Cell.

Decidua parietalis-derived mesenchymal stromal cells reside in a vascular niche within the choriodecidua

Reprod. Sci.

Placenta-derived stem cells: new hope for cell therapy?

Cytotechnology