title: Human umbilical perivascular cells (HUCPVCs): a novel source of mesenchymal stromal-like (MSC) cells to support the regeneration of the testicular niche.
abstract: The expansion of functional testicular biopsy-derived human spermatogonial stem cells (hSSC) ex vivo may enable the restoration of fertility in pre-pubertal males having undergone gonadotoxic therapies or men with severe male factor infertility. Various somatic cells are known to regulate SSC homeostasis and spermatogenesis in the developing and adult testis. Prior attempts to recapitulate this niche demonstrated the requirement of feeder cells, such as endogenous testicular somatic cells, for germ cell expansion ex vivo. However, this strategy has limitations in the expansion of hSSCs from tissue biopsies for which spermatogenesis is absent or defective. Our aim was to evaluate the first trimester human umbilical cord perivascular cells (FTM HUCPVCs), a novel source of mesenchymal stromal-like cells (MSCs), as potential human feeder cells for standardized hSSC expansion ex vivo. Targeted RNA sequencing analysis demonstrated that CD90+ve FTM HUCPVCs expanded in vitro under germ cell culture conditions express a profile of targeted testicular-associated transcripts that is similar to cultured human CD90+ve testicular adherent cells (hTACs) and secrete LIF, FGF2 and BMP4, key growth factors known to regulate spermatogenesis. We also demonstrated that mitotically inactivated FTM HUCPVCs support the expansion of mouse germ cells and putative SSCs ex vivo and that FTM HUCPVC transplantation promotes in vivo germ cell regeneration after mono-2-ethylhexyl phthalate (MEHP)-induced seminiferous tubule damage in a murine model, including a partial reconstitution of tubular cellular architecture and reestablishment of DAZL and acrosin+ve germ cell layers. Together, these data suggest that FTM HUCPVCs have phenotypical and functional properties that may support repair of the human testicular niche.
authors: CReATe Fertility Centre Toronto, Ontario, Canada.
authors: Leila
authors: L
authors: Maghen
authors: CReATe Fertility Centre Toronto, Ontario, Canada.
authors: Ekaterina
authors: E
authors: Shlush
authors: CReATe Fertility Centre Toronto, Ontario, Canada.|Pinchas Borenstein Talpiot Medical Leadership Program Sheba Medical Center, Tel HaShomer, Ramat Gan, Israel, affiliated with the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors: Itai
authors: I
authors: Gat
authors: CReATe Fertility Centre Toronto, Ontario, Canada.
authors: Melissa
authors: M
authors: Filice
authors: CReATe Fertility Centre Toronto, Ontario, Canada.
authors: Tanya A
authors: TA
authors: Barretto
authors: Division of Urology Mount Sinai Hospital, Toronto, Ontario, Canada.
authors: Keith
authors: K
authors: Jarvi
authors: Division of Urology Mount Sinai Hospital, Toronto, Ontario, Canada.
authors: Kirk
authors: K
authors: Lo
authors: CReATe Fertility Centre Toronto, Ontario, Canada.
authors: Andrée
authors: A
authors: Gauthier-Fisher
authors: CReATe Fertility Centre Toronto, Ontario, Canada.|Department of Obstetrics & Gynecology University of Toronto, Toronto, Ontario, Canada.|Department of Gynecology Women's College Hospital, Toronto, Ontario, Canada.
authors: Clifford L
authors: CL
authors: Librach