Renaissance caused by embryonic stem cells discovery in biomedical research raised hopes about their usage in SCI also [27]. Despite positive reports from experimental studies [17, 28], clinical usage of them is being delayed. Several reasons, such as tumorigenic potential in vivo [29] and legal and ethical issues [30] associated with embryonic stem cells, stalled their migration from bench to bedside [31]. This prompted a search for alternate sources of stem cells.

In a pursuit to find alternatives to embryonic stem cells, cells present in the connective tissue component of several organs were thought to be resident stem cells. These stromal cells were named somewhat inappropriately as mesenchymal stem cells (MSCs) as the word “mesenchyme” refers to embryonic connective tissue, whereas adult connective tissue should be referred as “stroma.”

Mesenchymal stem cells were discovered in various adult tissues such as skin [32, 33], bone marrow [34], Wharton’s Jelly [35], amniotic fluid [36], dental pulp [37], etc. Woodbury et al. [34] had shown MSCs could be induced to adopt neural lineage and that kindled more interest in using these cells for SCI repair. MSCs derived from different sources have been tested in SCI [38] and some of them were found to be beneficial.

Discovery of MSC did not conclude therapy for SCI as there were negative reports about MSC usage for SCI [39]. MSCs were also not free from immunological rejection [40]. This would mean undesirable need for immunosuppressive therapy if MSCs are used. Thus, it would be better to identify a prospective cell type for SCI repair which can be procured in plenty, immunologically naïve, and biologically safe. In this context, placenta-derived cells find their place as they can be obtained in large quantities without ethical and legal concerns and are found to be immunologically nonantigenic.

Placenta was found to harbor MSCs at various parts. Stromal cells derived from amniotic stroma [41, 42], decidua basalis and decidua parietalis [41], and umbilical cord blood cells [43] were shown to possess characteristic features of MSC. Through a series of publication, Sakuragawa et al. [44], reported neural and glial nature exhibited by amniotic epithelial cells which lead to the speculation of using these cells for treating neurological conditions. Later, amniotic epithelial cells were found to exhibit stem cell features [45] although amniotic epithelial cells do not have properties similar to MSCs.

It was intended to review the status of human amniotic epithelial cells (hAECs) for contusive SCI repair in the light of our own experiments conducted using hAEC in rat model of contusive SCI (unpublished work). We present here our observations which indicate high potentials of these cells in treating SCI. Scope of the phrase “amniotic epithelial cells” was limited to those epithelial cells derived directly from amniotic membrane and amniotic fluid cells are excluded. As amniotic fluid might contain not only epithelial cells shed off from amniotic membrane but also cells derived from the developing fetus, nature of amniotic fluid cells is ambiguous. Similarly, stromal cells obtainable from amnion (amniotic stromal cells) are also excluded as these cells express MSC features and not epithelial type features.

Postoperative period of the animals in general was uneventful. BBB scores of the hAEC transplanted animals in comparison with lesion group animals were given in Fig. 22.1. BBB score comprise of 21-point scale in which 0 represents complete paralysis and 21 indicates normal motor function in hind limbs. Spinal cord injured animals were with score zero immediately after lesions. However, there was a gradual recovery and by 8 weeks, hAEC transplanted animals reached a score of 15 which is about two points higher than lesion group. The difference was significant at 8 weeks postinjury/transplantation.

CellTracker Green was readily taken up by hAEC in culture and showed bright green fluorescence. hAEC was having either a round or slightly irregular morphology with a granular cytoplasmic appearance in vitro (Fig. 22.2). To discriminate between autofluorescing macrophage and CellTracker Green labeled hAECs, immunofluorescence study for macrophages was carried out using ED1 antibody. Also, hAEC transplantation carried out in uninjured animals served as control for such counter staining study. In uninjured cord, transplanted hAECs were seen to survive up to 2 weeks and there were no ED1 positive macrophages. In injury group, all the macrophages seen in green channel due to autofluorescence were positive for ED1. Interestingly, in hAEC group, there were cells seen in both green and red channels, i.e., macrophages and cells seen only in green channel which were negative for ED1. These cells were presumably the transplanted hAECs. These results are illustrated in Fig. 22.3.

Such green fluorescing ED1 negative cells were rare by 4 weeks and were not seen beyond that. Cresyl fast violet staining and silver staining showed cells with round morphology among host axons which were absent in lesion group animals (Fig. 22.4). These cells might be the transplanted hAECs. It was not known whether the cells lost their fluorescent label by 4 weeks of postinjury/transplantation period.

Numerical densities of neurons at various spinal segments were given in Fig. 22.5. Lesion group animals showed significant reduction in neurons when compared with control animals. In hAEC group, neuronal densities were less when compared with control animals; nevertheless, they were significantly higher than lesion group animals.