The possibility of using stem cells for regenerative medicine has opened a new field of investigation to find the best sources for obtaining multipotent stem cells, in particular through non-invasive procedures.
Initially defined as bone marrow precursors, new evidence suggests that MSCs are present in virtually all organs playing a possibly important role in tissue maintenance and regeneration [27–31]. More recently, they were also found in the human uterus endometrium and in menstrual blood and have been shown capable of promoting regeneration in vivo [16, 18, 19, 21, 22, 32, 33]. A recent study demonstrated isolating stem cells from the endometrium and promoting in vitro chondrogenesis .
It has been shown that MSCs obtained from the umbilical cord, dental pulp, adipose tissue and menstrual blood, all biological discards, are able to differentiate into muscle, fat, bone and cartilage cell lineages [7, 10, 12–15]. Here we show for the first time that the hFTs, which are discarded in hysterectomy procedures, are an additional source rich in MSCs, which we designated as human tube MSCs (htMSCs). Early passage htMSCs had longer PD times (approximately 15 hours). However, with additional passages, PD times shortened and stabilized. Although htMSCs proliferate extensively in culture, comparative analysis of the cells' karyotypes from early (second) and late (eleventh) passages showed no abnormalities, suggesting chromosomal stability throughout the passages.
Although Nasef et al. suggest that a purified Stro-1-enriched population augment the suppressive effect in allogeneic transplantation, Murphy et al. showed that allogeneic endometrial regenerative cells (ERC or menstrual blood mesenchymal stem cells), that are Stro-1 negative, were efficient for the treatment of critical limb ischemia in rats [34, 32]. In accordance to recent studies in human endometrium, htMSCs are also Stro1 negative . In other hand, CD44, which is considered a marker of MSCs and has been shown to be critical for the recruitment of MSCs into wound sites for tissue regeneration, was highly expressed in htMSCs and also in the fresh digested fallopian tube tissue [36, 37]. CD29, an integrin involved in cell adhesion was also greatly expressed in all htMSCs studied lineages, including freshly digested samples. Curiously, according to evidences from recent studies, this molecule may be involved in the fertilization process, allowing the binding and fusion of sperm and egg .
However, speculation that htMSCs may play a role in reproduction remains to be elucidated. Anyway, the high levels of expression of adhesion markers (CD29, CD44 and CD90) and other MSC markers (CD13, CD73, SH2, SH3 and SH4) together with the multilineage differentiation results confirmed the mesenchymal nature of human fallopian tube stem cells. These important features imply that htMSCs represent a cell population that can be rapidly expanded for potential clinical applications.
The morphological and functional integrity of the tubal epithelium are of paramount importance for the development of a unique microenvironment required for optimal fertilization and early embryo development. They are therefore essential for successful implantation as evidenced by a recent meta-analysis showing that the use of human oviductal cells for co-culture improves embryo morphology, implantation rates and pregnancy success .
Anatomically the hFTs are divided into four distinct segments (intramural, isthmic, ampulla, and infundibulum/fimbria) each one comprised of different populations of epithelial cells and distinct secretory activity . Bacteria and viruses constantly found in the lumen of the vagina may sporadically enter the upper reproductive tract disrupting the hFTs epithelial integrity, and represent a significant risk factor to female reproductive health. The need of a strict homeostasis of hFT environment in order to avoid the disruption of the reproductive function suggests that MSC niches present in this tissue could be responsible for this process [41, 42].
Recently, Wolff et al. were able to demonstrate the presence of endometrial multipotent cells by inducing chondrogenic differentiation in vitro of a subpopulation of endometrial stromal cells . However, using non-endometrial gynecologic tissue such as myometrium, fallopian tube, and uterosacral ligaments as controls, they could not demonstrate chondrogenesis. This suggests that there may be less progenitor stem cells in these tissues due to their lower burden of lifelong regeneration compared with the endometrium; or that the differentiation assay employed in their study was not appropriate for these tissues. Based on our success in obtaining myogenic, adipogenic, osteogenic, and chondrogenic differentiation from htMSCs we may presume that the inability to demonstrate chondrogenesis from fallopian tube tissue reported by Wolff et al. could be related to methodological issues rather than to progenitor stem cell concentration.