Intra-gonadal delivery of first trimester human umbilical cord perivascular cells (FTM HUCPVC) prior to chemotherapy has a protective effect in rodent models of alkylating agent-induced testicular and ovarian damage

FTM HUCPVCs have increased capacity for regeneration when compared to older sources of mesenchymal stromal cells (MSCs), promote restoration of germ cell lineages in a phthalate-induced testicular damage mouse model, are resistant to cyclophosphamide (CTX)-induced cytotoxicity, and maintain their regenerative properties when exposed to CTX in vitro. As such, we hypothesize that they may be a good cell therapy candidate for fertility preservation. Our objective was to determine whether FTM HUCPVCs engraft and prevent loss of fertility in rodent models of alkylating agent-induced gonadotoxicity when delivered to the testis or ovary prior to chemotherapeutic treatment. Pre-clinical study of male and female rodent models administered with FTM HUCPVCs prior to receiving gonadotoxic doses of alkylating chemotherapy. Busulfan (20mg/kg) was administered to CD1 mice 3 days after intra-testicular delivery of 50,000 FTM HUCPVCs. CTX (150-200mg/kg) was administered to Wistar rats following intra-ovarian delivery of 50,000 FTM HUCPVCs. Control groups included: untreated animals, animals untreated with chemo receiving intra-gonadal media injection, and animals treated with chemo following intra-gonadal injection of media. HUCPVC survival, ovarian follicles (female model) and tubules with active spermatogenesis (male model) were assessed using histological methods. Fertility profiles, sperm concentration and motility were assessed in the male study. When compared to media controls, female and male models receiving FTM HUCPVCs prior to CTX or busulfan treatment, showed a significant recovery in the number of primordial follicles (P<0.001) and proportion of tubules with active spermatogenesis (P<0.05), respectively. FTM HUCPVC-treated animals showed improved mating profiles and sperm parameters when compared to busulfan-treated controls (P<0.05). FTM HUCPVCs were detected in the testicular interstitial space and near blood vessels in the ovarian stroma. FTM HUCPVCs administered pre-alkylating drug therapy prevent gonadal damage in vivo. FTM HUCPVCs are therefore promising candidates for fertility preservation.