Application of Scaffold in Ovarian Transplantation for Female Fertility Preservation---An in vivo Transgenic Mouse Model (I)

Ovarian tissue cryopreservation and autotransplantation is a promising option for fertility preservation of female cancer patients to restore ovarian function and fertility. However, the post-transplantation window of ischemia limits the life span of the ovarian grafts. Thus, host and graft angiogenesis are potential targets to reduce the avascular period after transplantation. Tissue engineering is a promising field that aims at fabricating biological alternatives for harvested tissues and organs for transplantation. The scaffold can provide a suitable surface for cell attachment, proliferation, and differentiation, a porous network for uniform cell distribution for mass transport of soluble signaling molecules, nutrients, and metabolic waste removal, and a three-dimensional template guiding the growth of the tissue. Poly-L-lactide (PLLA) and its degradation products are biocompatible and have gained the approval of US Food and Drug Administration (FDA) for a variety of human clinical applications. Our preliminary data have showed an increased survival rate of allotransplanted gonad tissue with PLLA scaffolds in a transgenic mouse model with in vivo optical imaging. Its availability in acceleration of angiogenesis in the ovarian grafts needs to be investigated. In addition, we have reported that the antiapoptotic sphingosine-1-phosphate (S1P) protects vitrified ovarian grafts from ischemic reperfusion injury. Our preliminary data also showed the protective effect of S1P on busulfan-induced ovarian gonadotoxicity. The tissue-engineering scaffolds can be served as vehicles for sustained delivery of S1P, angiogenic factors, or antioxidants to improve neovascularization and to prevent ischemia following transplantation. Tissue engineering combining the principles of cell transplantation, materials science, and bioengineering may provide solutions to the problems. Our objectives are to evaluate the application of scaffold in the ovarian transplantation and establish a mouse model for real-time evaluation of the ovarian grafts and assessment of graft viability. Furthermore, with this model, we can evaluate angiogenesis of host and graft in vivo and the cellular and molecular alterations during angiogenesis and make strategies to promote neovascularization and to prevent ischemia and cell apoptosis. Finally, we try to develop a promising drug-delivery system to maximize the protective effect.