Human amniotic fluid stem cells have a potential to recover ovarian function in mice with chemotherapy-induced sterility

Abstract

BackgroundHuman amniotic fluid cells (hAFCs) may differentiate into multiple cell lineages and thus have a great potential to become a donor cell source for regenerative medicine. The ability of hAFCs to differentiate into germ cell and oocyte-like cells has been previously documented. Herein we report the potential use of hAFCs to help restore follicles in clinical condition involving premature ovarian failure.ResultsHuman amniotic fluid was obtained via amniocentesis, yielding a subpopulation of cloned hAFCs that was able to form embryoid bodies (EBs) and differentiate into three embryonic germ layers. Moreover, culture of EBs in medium containing human follicular fluid (HFF) or a germ cell maturation factor cocktail (FAC), expressed germ cells markers such as BLIMP1, STELLA, DAZL, VASA, STRA8, SCP3, SCP1, and GDF9. Furthermore, one cell line was grown from clone cells transfected with lentivirus-GFP and displaying morphological characteristics of mesenchymal cells, had the ability to restore ovarian morphology following cell injection into the ovaries of mice sterilized by intraperitoneal injection of cyclophosphamide and busulphan. Restored ovaries displayed many follicle-enclosed oocytes at all stages of development, but no oocytes or follicles were observed in sterilized mice whose ovaries had been injected with medium only (control). Notably, identification of GFP-labeled cells and immunostaining with anti–human antigen-specific antibodies demonstrated that grafted hAFCs survived and differentiated into granulosa cells which directed oocyte maturation. Furthermore, labeling of ovarian tissue for anti-Müllerian hormone expression, a functional marker of folliculogenesis, was strong in hAFCs-transplanted ovaries but inexistent in negative controls.ConclusionThese findings highlight the possibility of using human amniotic fluid-derived stem cells in regenerative medicine, in particular in the area of reproductive health.

Study of the reparative effects of menstrual-derived stem cells on premature ovarian failure in mice

“…In recent years, interest has rapidly grown in studies exploring the therapeutic potential of stem cells because of their potential to differentiate into various specialized cell types. This characteristic has been observed in stem cells derived from a number of different sources, including bone marrow [6–8], amniotic fluid [9], and adipose tissue [10, 11], and all of these cell types have been shown to have therapeutic effects on long-term infertility and ovarian damage. However, many of the suitable cell types currently identified for human use are either difficult to obtain or obtaining them involves invasive procedures.…”

Therapeutic potential of amniotic fluid stem cells to treat bilateral ovarian dystrophy in dairy cows in a subtropical region

“…Liu, Huang, Guo, Cheng, and Zou () indicated that human AFSCs can survive and proliferate in mice with premature ovarian failure; the cells may also restore ovarian function (Lai et al., ). In addition, AFSCs have anti‐inflammatory activity and are capable of repairing damaged tissues and organs (Bollini, Pozzobon, Nobles, Riegler, & Dong, ).…”

“…Specifically, it is considered abnormal when anestrous continues for more than 50-60 days following parturition (Rhodes, McDougall, Burke, Verkerk, & Macmillan, 2003). In tropical regions, bovine reproductive characteristics are considered to be decreased when anestrous continues for 150 days after parturition, and the high incidence can cause serious economic losses (Montiel & Ahuja, 2005 AFSCs can survive and proliferate in mice with premature ovarian failure; the cells may also restore ovarian function (Lai et al, 2013).…”

Potential therapeutic effect of amniotic stem cell transplantation on ovarian function and folliculogenesis in rats with induced ovarian failure

“…The restored ovarian cells developed follicles at all stages. Lai et al [3] strongly suggested that grafted human amniotic fluid cells (hAFCs) differentiated into granulosa, but not germ cells, and that implanted hAFCs directed follicle formation and may have aided folliculogenesis recovery by indirect trophism on ovarian tissue in the chemically damaged murine ovary evidenced by increased expression of AMH after hAFCs transplantation in the ovaries of sterilized mice. Conversely, AMH expression was negative in the positive control groups.…”

“…At present, about 25% of all forms of POF can be classified as iatrogenic and related to cancer treatment [3] such as chemotherapy or radiotherapy. Also, POI may be caused by autoimmunity, genetic factors such as Turner's syndrome, fragile X syndrome, and inhibin a gene variants.…”