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Butler J.M.,New York Medical College | Gars E.J.,New York Medical College | James D.J.,New York Medical College | James D.J.,Ronald relman and Claudia Cohen Center for Reproductive Medicine | And 4 more authors.
Blood | Year: 2012

Transplantation of ex vivo expanded human umbilical cord blood cells (hCB) only partially enhances the hematopoietic recovery after myelosuppressive therapy. Incubation of hCB with optimal combinations of cytokines and niche cells, such as endothelial cells (ECs), could augment the efficiency of hCB expansion. We have devised an approach to cultivate primary human ECs (hECs) in serum-free culture conditions. We demonstrate that co-culture of CD34+ hCB in direct cellular contact with hECs and minimal concentrations of thrombopoietin/Kit-ligand/Flt3-ligand resulted in a 400-fold expansion of total hematopoietic cells, 150-fold expansion of CD45+CD34+ progenitor cells, and 23-fold expansion of CD45+ Lin-CD34hi+CD45RA-CD49f+ stem and progenitor cells over a 12-day period. Compared with cytokines alone, co-culture of hCB with hECs permitted greater expansion of cells capable of multilineage engraftment and serial transplantation, hallmarks of long-term repopulating hematopoietic stem cells. Therefore, hECs establish a cellular platform for expansion of hematopoietic stem and progenitor cells and treatment of hematologic disorders. © 2012 by The American Society of Hematology. Source

Kofinas J.D.,New York Presbyterian Hospital | Elias R.T.,Ronald relman and Claudia Cohen Center for Reproductive Medicine
Women's Health | Year: 2014

Aim: To determine whether a follicle-stimulating hormone (FSH)/luteinizing hormone (LH) ratio over 3 in the setting of a normal FSH (<12 IU/l) is associated with a higher rate of failed controlled ovarian stimulation cycles. Design: Retrospective cohort. Materials & methods: A total of 676 patients were identified; 198 patients had a FSH/LH ratio >3 and 477 patients had a FSH/LH ratio <3. Exclusion criteria included: age >40 years; estradiol (E2) prime protocols; E2 at start >70 pg/ml; and FSH at start >12 IU/l. The main outcome measure was cycle cancellation. Results: An elevated FSH/LH ratio >3 was more likely to result in the individual's cycle cancelled (15 vs 5.24%; p = 0.0001). The total gonadotropin dosage was greater in the higher ratio versus lower ratio group (2636 vs 2242 IU; significant). Peak E2 was significantly lower in the FSH/LH >3 group (peak E2: 1635 vs 1942 pg/ml). Conclusion: The value of the FSH/LH ratio in patients with normal FSH levels, may have a role in determining the appropriate stimulation protocol and predict cycle cancellations. © 2014 Future Medicine Ltd. Source

Ginsberg M.,Howard Hughes Medical Institute | James D.,Howard Hughes Medical Institute | James D.,Ronald relman and Claudia Cohen Center for Reproductive Medicine | Ding B.-S.,Howard Hughes Medical Institute | And 14 more authors.
Cell | Year: 2012

ETS transcription factors ETV2, FLI1, and ERG1 specify pluripotent stem cells into induced vascular endothelial cells (iVECs). However, iVECs are unstable and drift toward nonvascular cells. We show that human midgestation c-Kit- lineage-committed amniotic cells (ACs) can be reprogrammed into vascular endothelial cells (rAC-VECs) without transitioning through a pluripotent state. Transient ETV2 expression in ACs generates immature rAC-VECs, whereas coexpression with FLI1/ERG1 endows rAC-VECs with a vascular repertoire and morphology matching mature endothelial cells (ECs). Brief TGFβ-inhibition functionalizes VEGFR2 signaling, augmenting specification of ACs into rAC-VECs. Genome-wide transcriptional analyses showed that rAC-VECs are similar to adult ECs in which vascular-specific genes are expressed and nonvascular genes are silenced. Functionally, rAC-VECs form stable vasculature in Matrigel plugs and regenerating livers. Therefore, short-term ETV2 expression and TGFβ inhibition with constitutive ERG1/FLI1 coexpression reprogram mature ACs into durable rAC-VECs with clinical-scale expansion potential. Banking of HLA-typed rAC-VECs establishes a vascular inventory for treatment of diverse disorders. © 2012 Elsevier Inc. Source

Kang H.-J.,Ronald relman and Claudia Cohen Center for Reproductive Medicine | Imperato-Mcginley J.,Weill Cornell Medical Center | Zhu Y.-S.,Weill Cornell Medical Center | Rosenwaks Z.,Ronald relman and Claudia Cohen Center for Reproductive Medicine
Fertility and Sterility | Year: 2014

A most interesting and intriguing male disorder of sexual differentiation is due to 5α-reductase-2 isoenzyme deficiency. These male infants are born with ambiguous external genitalia due to a deficiency in their ability to catalyze the conversion of T to dihydrotestosterone. Dihydrotestosterone is a potent androgen responsible for differentiation of the urogenital sinus and genital tubercle into the external genitalia, urethra, and prostate. Affected males are born with a clitoral-like phallus, bifid scrotum, hypospadias, blind shallow vaginal pouch from incomplete closure of the urogenital sinus, and a rudimentary prostate. At puberty, the surge in mainly T production prompts virilization, causing most boys to choose gender reassignment to male. Fertility is a challenge for affected men for several reasons. Uncorrected cryptorchidism is associated with low sperm production, and there is evidence of defective transformation of spermatogonia into spermatocytes. The underdeveloped prostate and consequent low semen volumes affect sperm transport. In addition, semen may not liquefy due to a lack of prostate-specific antigen. In the present review, we discuss the 5α-reductase-2 deficiency syndrome and its impact on human fertility. © 2014 American Society for Reproductive Medicine, Published by Elsevier Inc. Source

Reichman D.E.,Ronald relman and Claudia Cohen Center for Reproductive Medicine | White P.C.,University of Texas Southwestern Medical Center | New M.I.,Mount Sinai Hospital | Rosenwaks Z.,Ronald relman and Claudia Cohen Center for Reproductive Medicine
Fertility and Sterility | Year: 2014

Congenital adrenal hyperplasia (CAH) is the most frequently encountered genetic steroid disorder affecting fertility. Steroid hormones play a crucial role in sexual development and reproductive function; patients with either 21- hydroxylase or 11β-hydroxylase deficiency thus face immense challenges to their fertility. Given the relevance of CAH in reproductive medicine as well as the diagnostic challenges posed by the phenotypic overlap with polycystic ovary syndrome, we review the reproductive pahophysiology of both classic and nonclassic CAH and present contemporary treatment options. © 2014 American Society for Reproductive Medicine, Published by Elsevier Inc. Source

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