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Human CD133+ bone marrow-derived stem cells promote endometrial proliferation in a murine model of Asherman syndrome  Irene Cervelló, Ph.D., Claudia Gil-Sanchis,

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Presentation on theme: "Human CD133+ bone marrow-derived stem cells promote endometrial proliferation in a murine model of Asherman syndrome  Irene Cervelló, Ph.D., Claudia Gil-Sanchis,"— Presentation transcript:

1 Human CD133+ bone marrow-derived stem cells promote endometrial proliferation in a murine model of Asherman syndrome  Irene Cervelló, Ph.D., Claudia Gil-Sanchis, Ph.D., Xavier Santamaría, M.D., Ph.D., Sergio Cabanillas, M.D., Ph.D., Ana Díaz, Ph.D., Amparo Faus, B.Sc., Antonio Pellicer, M.D., Ph.D., Carlos Simón, M.D., Ph.D.  Fertility and Sterility  Volume 104, Issue 6, Pages e3 (December 2015) DOI: /j.fertnstert Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions

2 Figure 1 Study design. (A) Human CD133+ bone marrow-derived stem cells (BMDSCs) isolated from patients with Asherman syndrome (AS) were labeled with superparamagnetic iron oxide nanoparticles. Human-labeled cells were injected into immunodeficient mice with AS intrauterinely (group A) or by tail vein (group B). Uteri were excised after 90 (group A) or 12 days (group B) and subjected to Prussian blue, Ki67 and trichrome staining, as well as analyzed for paracrine gene expression. (B) Table showing the phenotypic characterization of human CD133+ BMDSCs from 10 patients. Fertility and Sterility  , e3DOI: ( /j.fertnstert ) Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions

3 Figure 2 Generation of Asherman syndrome in NOD-SCID mice. Asherman syndrome was induced in NOD-SCID mice (N = 10) by the insertion and rotation of a needle carrying Indian ink in the uterine lumen. Uteri were analyzed macroscopically (A), to note the presence of Indian ink to identify the specific site of damage and microscopically (B and D), using Trichrome staining to visualize the damage to the endometrium. Leiomyoma tissue was used as positive control (C). Fertility and Sterility  , e3DOI: ( /j.fertnstert ) Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions

4 Figure 3 Engraftment of superparamagnetic iron oxide nanoparticle-labeled human CD133+ bone marrow-derived stem cells into the damaged endometrium. (A and B) Prussian blue staining (blue spots) in uterus, liver, spleen, and kidney of mice treated with intrauterine injection (A) and mice treated with tail vein injection (B). Images are represented at ×40 and ×100 magnification. (C) Liver, spleen, lung, and kidney tissue controls from nontreated mice. Images are represented at ×40 magnification. Fertility and Sterility  , e3DOI: ( /j.fertnstert ) Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions

5 Figure 4 Proliferation induction in an Asherman syndrome-like endometrium by CD133+ bone marrow-derived stem cells. (A) Ki67 antigen staining for treated and nontreated mice from intrauterine injection and from tail vein injection (B). Images were taken at ×40 and ×100 magnification. Graphics bars representing gene expression of paracrine factors (Bmp6, Pdgfβ, Thbs1, Tnfα, and Igf1) and the quantification of Ki67+ cells are presented as percentages of mean ± SEM. *Denotes statically significant differences. Fertility and Sterility  , e3DOI: ( /j.fertnstert ) Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions

6 Supplemental Figure 1 Flow cytometry results for superparamagnetic iron oxide nanoparticle-labeled CD133+ bone marrow-derived stem cells by Rhodamine staining. Fertility and Sterility  , e3DOI: ( /j.fertnstert ) Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions

7 Supplemental Figure 2 Positive (intestine) and negative (brain) controls for Ki67 immunohistochemistry. Fertility and Sterility  , e3DOI: ( /j.fertnstert ) Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions


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