Table 2 Various studies reporting beneficial effects of mesenchymal cells to restore ovarian function after chemoablation in animal models

Wang et al. [107]

Menstrual blood mono-nuclear cells were transplanted via intra-peritoneal route into mice chemoablated with cisplatin. The transplanted cells localized into ovarian interstitium. Following transplantation, follicle numbers increased and levels of sex hormones reached normalcy and improved ovarian function.

Fouad et al. [108]

The study compared the efficiency of human amniotic membrane and adipose derived MSCs following transplantation into cyclophosphamide induced ovarian failure. Transplantation of MSCs from both sources showed increased number of follicles and oocytes alongwith increase in serum estradiol and decrease in serum FSH compared to chemoablated controls. The efficacy was more using human amniotic membrane MSCs.

Song et al. [109]

In cyclophosphamide induced POF rat model human umbilical cord MSCs were transplanted by using either tail intravenous injection or injection into ovary in situ. Following transplantation, folliculogenesis was recovered along with hormonal secretions and decreased ovarian cell apoptosis.

Kilic et al. [110]

Transplantation of bone marrow MSCs into cyclophosphamide treated rat showed protective effects by reducing germ cell apoptosis and DNA damage. Increased primordial follicular counts were obtained following transplantation compared to controls.

Liu et al. [111]

Bone marrow derived MSCs were transplanted into POF rat model obtained by cisplatin treatment. The transplanted group showed increase in follicle growth and estradiol levels compared to control, thereby restoring ovarian structure and function.

Liu et al. [112]

Transplantation of human endometrial MSCs into POF mouse model induced by cyclophosphamide showed survival of transplanted cells in ovaries and upregulation of ovarian markers along with increased estradiol and follicle number compared to control and restoring ovarian function.

Lai et al. [113]

Following transplantation of skin derived MSCs from male/female mice into recipient mice with busulphan and cyclophosphamide induced ovarian damage, partial restoration of fertility was observed. Transplanted MSCs grafted into host ovaries and increased expression of oogenesis markers was observed compared to controls.

Abd Allah et al. [114]

MSCs from bone marrow of male rabbits were injected intravenously into female rabbits chemoablated with cyclophosphamide. Increase in follicle numbers and resumption of normal follicular structure was observed compared to controls by histology. Ovarian tissues showed presence of Y-chromosome containing donor cells indicating engrafting of transplanted cells.

Wang et al. [115]

Umbilical cord MSCs were transplanted intravenously into POF mouse model made by cyclophosphamide treatment. Reduced apoptosis in cumulus cells, increased number of follicles and recovery of ovarian function was observed.

Liu et al. [116]

Transplantation of human amniotic fluid cells (CD44+/CD105+) showed survival into cyclophosphamide induced POF mice models for atleast 3 weeks following transplantation and proliferated.

Selesniemi et al. [117]

Bone marrow mono-nuclear cells from young adult female mice (with EGFP transgene under β-actin) were transplanted into young/middle aged females. Following this treatment, the fertile potential of the aging female was sustained for longer period than the normal reproductive senescence. Offsprings did not show EGFP expression. However, donor bone marrow derived somatic cells accumulate in recipients indicating efficient donor cell engraftment.

Fu et al. [118]

Effect of MSC transplantation on ovarian damage induced by chemotherapy using cyclophosphamide in rats was studied. Cultured MSCs were labelled with GFP and transplanted directly into bilateral ovaries. Following transplantation, the ovarian function was improved. Reduced germ cell apoptosis and upregulation of Bcl-2 was found in vivo.