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Table 1 Preclinical study of stem cell therapy on POF

From: Recent trends in stem cell therapy for premature ovarian insufficiency and its therapeutic potential: a review

Category Stem cell type Summary Transplantation Details Reference
Chemically induced model UCMSC ■ UCMSCs restore the ovarian function after paclitaxel injection through a direct triggering effect on the ovarian epithelium and/or indirect enrichment of ovarian niche through regulating tissue expression of CK 8/18, TGF-ß and PCNA (epithelial tissue, growth factor etc) injection of HCB-MSCs [31]
■ UCMSCs restore disturbed hormone secretion and folliculogenesis by reducing GC apoptosis. UCMSCs could reside in ovarian tissues and could survive for a comparatiely long time without obvious proliferation. 1 × 106 UCMSCs intravenous injection [32]
■ UCMSC treatment restores ovarian function by increasing follicular number, decreasing FSH serum and increasing AMH serum 5 × 105 UCMSCs injected via intraovarian route [33]
■ UCMSCs could reduce ovarian failure due to premature senescence caused by chemotherapy, and the NGF/TrkA signaling pathway was involved in the amelioration of POF. 5 × 106 UCMSCs injected intravenously [34]
■ Serum levels of E2, LH, VEGF in hAMSC and UCMSC transplanted groups were greater and FSH level was lower. Transplantation restored damaged ovarian function. 1 × 106 UCMSCs and h-AMSCs intraovarian injection [24]
BMMSC ■ Estradiol level dropped and FSH level rised 21 days after MSC therapy Damaged ovaries after chemotherapy regain functions after transplantation. 0.5 × 106 BMMSCs injected through the tail vein [23]
■ BM-MSC transplantation produces healthier ovarian follicles and less apoptosis of ovarian cells 1 × 106 BM-MSCs injected via tail IP [35]
■ The significant reduction of atretic follicle and significant increase of antral follicle and secondary follicle were observed in ovaries of BMSCs-treated mouse. mRNA expression levels of Nano3, Nobox, Lhx8 increased. 2 × 106 BMMSCs injected via tail vein [36]
■ Restore ovarian hormone production (FSH, AMH), reactivate folliculogenesis 5 × 105 BMSCs injected via intraovarian route [13]
■ BMMSC treatment resulted in higher numbers of preovutory follicles, metaphase II oocytes, 2-cell embryos, promoted ovarian vascularization, reduced apoptosis 1 × 106 BMMSCs IP injection [37]
FGSCs ■ Transplanted FGSCs restored function of premature ovarian failure and generated offspring in mice model. 1 × 104 FGSCs injected [30]
MenSCs ■ MenSC reduce apoptosis in granulosa cells, reduce fibrosis of ovarian interstitium, increase follicular numbers, reparative effects on damaged ovaries by secreting FGF2 2x106MenSCs [26]
■ MenSCs regulate normal follicle development, estrous cycle, reduce apoptosis in ovaries and activate ovarian transcriptional expression in ECM-dependent FAK/AKT signaling pathway 1x106MenSCs IP injection [6]
CP-MSCs ■ Restored serum hormone level and ovarian function 2 × 106 chorionic plate-derived MSCs injected via tail vein [38]
hPMSC ■ Inhibits granulosa cell apoptosis and follicular atresia by upregulating expression of AMH and FSHR in granulosa cells 1x106hPMSCs injected via tail vein [25]
■ hPMSC transplantation induces ZP3 immunization and restores ovarian function associated with PI3k/Akt signal pathway 1 × 106hPMSCs IP injection [39]
■ hPMSC transplantation reduces apoptosis of GC by regulating the expression of IRE1-alpha pathway of ER stress in ovaries 1 × 106 hPMSCs injected via tail vein [40]
■ PBMCs combined with PRP restore ovarian function by increasing ovarian neovascularization, folliculogenesis and reducing GC apoptosis 4 × 106 PBMCs IP injection [41]
ADSCs ■ Exosomes derived from hADSCs improve ovarian function by improving follicle numbers and inhibiting apoptosis rate 1x106hADSCs injected via intraovarian route [27]
■ Adipose tissue-derived MSCs improve follicular count, AMH and E2 levels, and related gene expressions (CXCL12, BMP-4, TGF-β, IGF-1) 1 × 106AT-MSCs IP injection [42]
■ ADSCs transplantation on collagen scaffolds improved fertility of rats with ovarian damage. 2 × 106 ADSCs injected via intraovarian route [43]
hAD-MSCs ■ hAD-MSCs inhibit chemotherapy-induced GC apoptosis, promote angiogenesis, regulate follicular development by upregulating Bcl-2 expression. 4x106hADMSCs IP injection [28]
BMMSC, OSC ■ The in-vivo transplantation of OSCs can be more effective protectors than BMMSCs for follicle maturation after chemotherapy. Unfortunately, the source of OSSCs is still a limitation for clinical applications. 2 × 106 BMMSCs and OSSCs injected intraperitoneally [44]
Naturally aged model hUCMSC ■ hUCMSC increase E2 and AMH, decrease FSH. Improves follicle number and expression of HGF, VEGF, IGF-1 1x106hUCMSCs injected via tail vein [14]
hAMSC, hAEC ■ hAMSCs are more effective in improving ovarian function than hAECs based on its telomerase activity, pluripotent marker expression levels, cytokine secretion. Intraovarian injection [45]
hADSC ■ HGF and bFGF derived from hADSCs improved ovarian function during natural aging via reduction of oxidative stress by activating the SIRT1/FOXO1 signaling pathway. Intraovarian injection [15]
BMSC ■ intra-ovarian injection of BMSCs changed the gene expression but did not recover granulosa cells or ovarian tissue. 1 × 107 BMSCs intraovarian injection [22]
hEPC ■ hEPCs attenuates reproductive aging and dysfunction potentially via regulation of inflammation, apoptosis and ER stress. 5x104hEPCs injected via tail vein [46]
Genetic causes AFSC ■ AFSC-derived exosomes contain miR-146a and miR-10a which inhibit apoptosis in damaged GCs and prevent ovarian follicles from atresia Direct injection [47]
miR-21-MSCs ■ miR-21 overexpression in MSC decreases apoptosis, downregulate PTEN and PDCD4, icrease E2, decrease FSH. 1 × 106 MSCs injected into the bilateral ovaries [48]
hAEC exosomes ■ hAEC exosomes increased number of follicles, inhibited GCs apoptosis by transferring miR-1246 which targets the apoptosis pathway. 1.6 × 109 particles injected via tail vein [49]
Surgical model ADSCs ■ Adipose derived mesenchymal stem cells can prevent the destructive effects of ischemia reperfusion injury on grafted ovaries through reducing oxidative stress and inflammation leading to improvement in the follicular pool and the endocrine function of the autografted ovaries. 5 × 104 ADSCs injected via intraovarian route [55]
PD-MSC ■ Spheroid-cultured PD-MSC transplantation increases estrogen and folliculogenesis-related gene expressions in Ovx rats 1 × 106 PD-MSC harvested, 100,000 cells directly injected into ovary [50]
  1. UCMSC umbilical cord mesenchymal stem cell, AFSC Amniotic Fluid Stem Cell, CP-MSCs Chorionic plate-derived mesenchymal stem cells, BMMSC bone marrow derived mesenchymal stem cells, FGSC Female germline stem cell, MenSC Menstrual blood-derived stem cell, hPMSC human placenta-derived mesenchymal stem cells, ADSC adipose derived mesenchymal stem cell, hAD-MSC human amnion derived mesenchymal stem cell, OSC ovarian stem cell, hAMSC human amniotic mesenchymal stromal cells, hAEC human amniotic epithelial cell, hEPC human endothelial progenitor cell, PD-MSC placenta derived mesenchymal stem cell