Lucía de Miguel-Gómez1, Sara López-Martínez2, Hannes Campo2, Emilio Francés-Herrero1, Amparo Faus2, Ana Díaz3, Antonio Pellicer4, Francisco Domínguez2, Irene Cervelló5. 1. Fundación Instituto Valenciano de Infertilidad, Instituto de Investigación Sanitaria La Fe, Valencia, Spain; University of Valencia, Valencia, Spain. 2. Fundación Instituto Valenciano de Infertilidad, Instituto de Investigación Sanitaria La Fe, Valencia, Spain. 3. University of Valencia, Valencia, Spain. 4. IVIRMA, Rome, Italy. 5. Fundación Instituto Valenciano de Infertilidad, Instituto de Investigación Sanitaria La Fe, Valencia, Spain. Electronic address: irene.cervello@ivirma.com.
Abstract
OBJECTIVE: To study the effect of human plasma from different sources, namely, umbilical cord blood and adult blood platelet-rich plasma (PRP), on the regeneration of endometrial damage. DESIGN: Composition analysis, in vitro approaches, and a preclinical murine model using plasma to promote endometrial regeneration. SETTING: Hospital and university laboratories. PATIENT(S)/ANIMAL(S): Adult plasma from four Asherman syndrome/endometrial atrophy patients and one fertile woman, commercial umbilical cord plasma, and uterine-damaged NOD/SCID mice model were used. INTERVENTION(S): Endometrial stromal cells from primary culture and an endometrial stem cell line were cultured in vitro, and uterine-damaged NOD/SCID mice were treated with plasma samples from several origins. MAIN OUTCOME MEASURE(S): To investigate the possible beneficial effects of PRP from Asherman syndrome/endometrial atrophy patients. To test if plasma from human umbilical cord blood had a stronger effect than adult PRP in endometrial regeneration. To demonstrate if PRP from Asherman syndrome/endometrial atrophy patients was as effective as PRP from a healthy woman and could therefore be used for autologous treatment. RESULT(S): All plasma samples contained molecules with a high potential for regeneration (stem cell factor, platelet-derived growth factor BB, thrombospondin-1, von Willebrand factor). Furthermore, the highest increase in in vitro proliferation and migration rate was found when endometrial stromal cells were treated with umbilical cord plasma; adult PRP also revealed a significant increment. In the mouse model, a higher expression of Ki67 and Hoxa10 in the endometrium was detected after applying adult PRP, and the proteomic analysis revealed a specific protein expression profile depending on the treatment. The damaged uterine tissue showed more proregenerative markers after applying umbilical cord plasma (Stat5a, Uba3, Thy1) compared with the other treatments (nonactivated umbilical cord plasma, activated adult PRP, and no treatment). CONCLUSION(S): Human PRP possesses regeneration properties usable for endometrial pathologies. Besides that, these regenerative effects seem to be more apparent when the source of obtaining is umbilical cord blood.
OBJECTIVE: To study the effect of human plasma from different sources, namely, umbilical cord blood and adult blood platelet-rich plasma (PRP), on the regeneration of endometrial damage. DESIGN: Composition analysis, in vitro approaches, and a preclinical murine model using plasma to promote endometrial regeneration. SETTING: Hospital and university laboratories. PATIENT(S)/ANIMAL(S): Adult plasma from four Asherman syndrome/endometrial atrophypatients and one fertile woman, commercial umbilical cord plasma, and uterine-damaged NOD/SCIDmice model were used. INTERVENTION(S): Endometrial stromal cells from primary culture and an endometrial stem cell line were cultured in vitro, and uterine-damaged NOD/SCIDmice were treated with plasma samples from several origins. MAIN OUTCOME MEASURE(S): To investigate the possible beneficial effects of PRP from Asherman syndrome/endometrial atrophypatients. To test if plasma from human umbilical cord blood had a stronger effect than adult PRP in endometrial regeneration. To demonstrate if PRP from Asherman syndrome/endometrial atrophypatients was as effective as PRP from a healthy woman and could therefore be used for autologous treatment. RESULT(S): All plasma samples contained molecules with a high potential for regeneration (stem cell factor, platelet-derived growth factor BB, thrombospondin-1, von Willebrand factor). Furthermore, the highest increase in in vitro proliferation and migration rate was found when endometrial stromal cells were treated with umbilical cord plasma; adult PRP also revealed a significant increment. In the mouse model, a higher expression of Ki67 and Hoxa10 in the endometrium was detected after applying adult PRP, and the proteomic analysis revealed a specific protein expression profile depending on the treatment. The damaged uterine tissue showed more proregenerative markers after applying umbilical cord plasma (Stat5a, Uba3, Thy1) compared with the other treatments (nonactivated umbilical cord plasma, activated adult PRP, and no treatment). CONCLUSION(S): Human PRP possesses regeneration properties usable for endometrial pathologies. Besides that, these regenerative effects seem to be more apparent when the source of obtaining is umbilical cord blood.