How Immunomodulatory Function Of Adipose-Derived Stem Cells Combined With Collagen Contributes To The Restoration Of Premature Ovarian Failure

Premature ovarian failure,which can be associated with female reproductive health,is becoming a worldwide concern.The mechanisms underlying this problem are urgently supposed to be addressed,which will promote the investigation of POF in clinic.Mice appear the same symptoms as POF after the treatment with cyclophosphamide.The applications of different injection methods with Adipose derived stem cells(e.g.inject directly,inject with biodegradable gel,inject through tail vein)in the restoration of infertile mice achieve various curative effects.The gel provides a long-term retention of ADSCs in a 3-dimensional niche with better viability,then the effect will repair the injured ovary histologically and functionally.ADSCs increased activity of Treg cells by inhibiting its apoptosis level,and achieve the immunologic balance in the ovary.Based on the previous studies,we proposed that Treg cells lack expression of ABCB1 that nonregulatory counterparts possess,rendering them susceptible to programmed cell death induced by cyclophosphamide.The imbalance of immunologic properrties due to amounts of reduced Treg cells in ovary severely triggered the autoimmune reactivity,resulting in the damage of female reproductive system.The transplantation of ADSCs could inhibit the apoptosis of Treg cells by 3 pathways,including cell-cell contact,secreting TGF-P,PEG2,and inducing the migration of Treg cells from other organs to the ovary.In summary,ADSCs may remedy POF through the modulation of immunosuppressive properties of Treg cells,displaying a clinically promising strategy in the treatment of infertility.