Importantly, amnion is easily obtained after caesarian delivery because the placenta, amniotic fluid, and membrane are typically discarded after childbirth. This procurement avoids the controversies associated with obtaining human embryonic stem cells and BMMSCs. Thus, the use of AM and amniotic fluids (AF) is highly promising innovative allografts and stem cell therapies for degenerative disorders where existing treatments have failed, such as plantar fasciosis and Achilles tendinosis.
AF derived cells are able to replicate rapidly and take 20– 24 hours to double in cell number, faster than both umbilical cord stem cells (28–30 hours) and BMMSCs (30+ hours) [11]. The progenitor cells also have a high self-renewal capacity with more than 300 population doublings [12]. In addition, only 30% of MSCs extracted from a child’s umbilical cord shortly after birth can be extracted and differentiated. In contrast, the success rate for AF derived MSCs has been close to 100%. Importantly, unlike other multipotent stem cells, particularly those with high self-renewal capacity, the risk of cancer development is low, and AF progenitor cells do not form teratomas in vivo [13].
In addition to multipotent stem cells, AF also contains a number of nutrients and growth factors that encourage fetal growth and protection. These factors are highly advan- tageous in regenerative clinical applications and aid tissue repair. Specifically, AF contains carbohydrates, proteins and peptides, lipids, lactate, pyruvate, electrolytes, enzymes, and hormones, transforming growth factor alpha (TGF-a), trans- forming growth factor beta 1 (TGF-b1), and fibroblast growth factor (FGF). A recent study demonstrated the effectiveness of FGF in restoring the morphologic and biomechanical properties of injured tendons in rabbits [14].
AF and AM have also been shown to have significant antimicrobial properties, mediated by a-defensins (human neutrophil defensins 1–3), lactoferrin, lysozyme, bacterici- dal/permeability-increasing protein, calprotectin, secretory leukocyte protease inhibitor, psoriasin, and cathelicidin [15]. Human beta-defensin-2 is another natural antimicrobial peptide present in the AF that may account for much of its antimicrobial activity [16]. Furthermore, lactoferrin, a glycoprotein secreted into the AF by neutrophils and amniotic cells, has bacteriostatic and bactericidal activity
[17]. Human AF also contains factors known to minimize scarring. Hyaluronic acid (HA) is abundant in AF and fetal HA is thought to inhibit collagen deposition to prevent fibrotic tissue formation [18, 19]. In recent studies addressing the effect of AF on proteases important for wound healing, human AF was shown to enhance collagenase activity but to inhibit activation of hyaluronidase, elastase, and cathepsin [20, 21].
Due to its regenerative, anti-microbial and anti-scarring properties the amnion has been used as an effective wound dressing and as a graft for skin wound coverage. Several stud- ies have highlighted the low immunogenicity of human amni- otic epithelial cells following transplantation into human volunteers. For example, no signs of acute rejection were observed after amnion was transplanted into subcutaneous pouches in normal human volunteers [22]. Following trans- plantation of amniotic tissues HLA antibodies are absent in serum samples [23]. In addition, amnion surface epithelial cells do not express HLA-A, HLA-B, HLA-C, or HLA-DR or b2-microglobulin [23, 24]. This, at least in part, explains why amniotic tissues can be used successfully as a skin graft without concern for tissue typing and matching of the donor to the host [8]. This lack of immunogenicity has been described in numerous clinical studies and is termed immune privilege [25].