until the 1970s when the human immunodeficiency virus/acquired immunodeficiency syndrome became epidemic, and its source was unclear (24). AM was no longer favorable as a treatment choice until Kim and Tseng (25), in 1995, presented their findings. Subsequently, published research has been increasing. In 2007, a technique was developed that allowed for aseptic recovery and preservation of viable cells and proteins (26). The wounds treated with AM responded to a protocol that allowed coverage of tissues as diverse as exposed bowel, pleura, pericardium, blood vessels, tendon, nerve, and bone. Wounds unresponsive to standard therapeutic measures have also responded to application of AM, and human AM dressings have become a useful adjunct in the care of complicated wounds (27).
Reports on the immunogenicity of human amniotic epithelial cells after transplantation into human volunteers have also been published (28–30). Amnion, consisting of a monolayer of epithelium on a basement membrane with an underlying collagen matrix containing a few fibroblasts (which, in theory, would express HLAs, although the epithelium itself lacks them), has been transplanted into subcutaneous pouches in normal human volunteers. None of the volunteers showed clinical signs of acute rejection, and amniotic epithelial cells were demonstrated by biopsy up to 7 weeks after implantation. HLA antibodies were not detected in serum samples, and no in vitro lymphocyte reaction to the amniotic cells was found in 2 of the volunteers. These results suggest that acute immune rejection does not occur after allotransplantation of human amniotic epithelial cells. These investigators suggested that if an immune response to the graft occurred, it was low grade and chronic rather than active and ineffective, because the amniotic epithelial cells appeared to survive and proliferate (28–30). AF progenitor cells do not form teratomas in vivo (31). In 1979, Trelford and Trelford-Sauder (32) found that AM transplantation promoted epithelial healing, reduced inflammation, increased comfort, and decreased the severity of insufficient vascu-larization. In 2002, Ucakhan et al (33) did not find any infectious, inflammatory, or toxic reactions related to AM transplantation. Amnion surface epithelial cells do not express HLA- A, -B, -C, or -DR or b2-microglobulin (34,35). Ucakhan et al (33) evaluated safety and efficacy of nonpreserved AM transplantation with or without limbal autograft transplant in acute and chronic eye injuries. In the transplantation of human organs, whether skin, kidney, liver, or other tissue, the major problem has been rejection of the grafted tissue owing to the host immune response. Despite this risk, amnion has been used successfully as a skin graft without concern for tissue typing and matching of the donor to the host (32).
This unique attribute (the lack of immunogenicity) has been described in numerous clinical studies and scientific journals and has led to the characterization of the placental organ as immune privileged. Thus, granulized AM and AF (gAM-AF) has been considered by many to be ideal for use in all patients, including the most immunocom-promised, such as post-transplant and human immunodeficiency virus-positive patients, and others with compromised immune systems, who could be adversely affected by human tissue transplantation or infection. The unique biologic structure of amniotic tissue, coupled with the low risk of an adverse host immune response, makes gAM-AF ideal for an in vivo wound covering.
Experimental and clinical studies have demonstrated that AM transplantation promotes re-epithelialization, decreases inflammation and fibrosis, and modulates angiogenesis (35). Several growth factors produced by AM are involved in these processes, including TGF-b and basic FGF (36).
Zhang et al (37) described the presence of MSCs in human placenta that were able to differentiate into osteogenic, adi-pogenic, and chondrogenic lineages and able to suppress T-cell proliferation.