Research On Novel Biomaterials For Repairing Ovarian Function Damage Based On Proteins Secreted By Mesenchymal Stem Cells

Primary ovarian insufficiency(POI)or premature ovarian failure(POF),is a clinical syndrome that leads to the loss of ovarian activity before the age of 40.It is characterized by amenorrhea lasting more than four months,which results from increased follicle-stimulating hormone(FSH)and decreased estradiol(E2)levels,and FSH should more than 40U/L two times with internal four weeks.POI can cause multiple problems,including perimenopausal syndrome,osteoporosis,an increasing risk of adverse cardiovascular events.Moreover,it is a major cause of infertility.POI can affect female healthy and quality of lives seriously.Commonly,the classical treatment in clinic is hormone replacement therapy(HRT),which can relieve symptoms,and improve quality of lives.However,HRT is limited because it may increase the risk of thrombolysis and tumor like breast cancer and endometrial cancer,furthermore,HRT cannot restore ovarian function.So reversing ovarian function failure is the key for solving this problem.Mesenchymal stem cells(MSCs)play an important role in reversing ovarian function.However,it is difficult to implant living MSCs because the loss of MSCs which affects the therapeutic effect.In addition,living MSCs may have potential biological safe problems such as autoimmune reaction or tumorgenesis.A number of subjects and reports revealed,that,MSCs can regenerate injury tissue or organs depending on paracrine function instead of MSCs differentiation directly.Therefore,improving the efficacy of mesenchymal stem cell therapy,reducing cell loss and risks are the issues.The aim of this project is that producing Ovarian Regenerative Patch(ORP)which depends on the biological pelvic materials loaded sustained-release particles encapsuled mesenchymal stem cells secretomes to reverse ovarian function.Multiple evidences based on molecules,cells and animals,ORP has been demonstrated its efficacy,such as effective delivery,single administration,long-term effect for hormone secreting,promoting follicle development and ovulation to prevent female aging.Then,we test the biocompatibility and safety of ORP.ORP cannot increase the risk of acute local inflammation and spring malformation and growth.At last,we detect the potential mechanism of ORP on ovarian dysfunction reversing.ORP can decrease the apoptosis of ovarian granulosa cells(OGCs)and increase the proliferation of OGCs,then it can increase the proliferation of surrounding vessels.Over to all,this project design and produce Ovarian Regenerative Patch.It can be a new medical device for ovarian restore and improve fertility.In the future,ORP will be used in clinic widely to benefit female.