title: The restorative effects of adipose-derived mesenchymal stem cells on damaged ovarian function.
abstract: The clinical application of human adipose-derived mesenchymal stem cells (MSCs) as treatment for intractable diseases or traumatic tissue damage has attracted attention. To address the ability of reactivating injured ovaries, we prepared a rat model with damaged ovaries by using an anticancer agent, cyclophosphamide (CTX). We then investigated the restorative effects on ovarian function and the safety of adipose-derived MSCs (A-MSCs). MSCs were shown to be capable of inducing angiogenesis and restoring the number of ovarian follicles and corpus lutea in ovaries. No deformities, tumor formation or deaths were observed in F1 and F2 rats, indicating that the local injection of MSCs into the ovary did not have any obvious side effects. In addition, the localization of the Y chromosome was investigated using the fluorescent in situ hybridization method by injecting male A-MSCs into the ovaries; as a result, the Y chromosomes were localized not in the follicles, but in the thecal layers. ELISA revealed that A-MSCs secreted higher levels of vascular endothelial cell growth factor (VEGF), insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) than tail fibroblast cells. Quantitative real-time PCR and immunohistochemistry showed that higher expression levels of VEGF, IGF-1 and HGF were observed in CTX-treated ovaries after A-MSC transplantation. These findings suggest that MSCs may have a role in restoring damaged ovarian function and could be useful for regenerative medicine.
authors.affiliation: Kato Ladies Clinic, 7-20-3 Nishishinjuku, Shinjuku-ku, Tokyo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takehara
authors.forename: Akiko
authors.initials: A
authors.lastname: Yabuuchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Ezoe
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kuroda
authors.forename: Rie
authors.initials: R
authors.lastname: Yamadera
authors.forename: Chiaki
authors.initials: C
authors.lastname: Sano
authors.forename: Nana
authors.initials: N
authors.lastname: Murata
authors.forename: Takuya
authors.initials: T
authors.lastname: Aida
authors.forename: Ken
authors.initials: K
authors.lastname: Nakama
authors.forename: Fumihito
authors.initials: F
authors.lastname: Aono
authors.forename: Naoki
authors.initials: N
authors.lastname: Aoyama
authors.forename: Keiich
authors.initials: K
authors.lastname: Kato
authors.forename: Osamu
authors.initials: O
authors.lastname: Kato
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D000911:Antibodies, Monoclonal; D003338:Corpus Luteum / Q000473:pathology; D003520:Cyclophosphamide / Q000633:toxicity; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008098:Litter Size; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D010049:Ovarian Diseases / Q000139:chemically induced / Q000503:physiopathology* / Q000628:therapy*; D006080:Ovarian Follicle / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D017931:DNA Primers; D036341:Intercellular Signaling Peptides and Proteins; D003520:Cyclophosphamide