Treating intrauterine adhesion using conditionally reprogrammed physiological endometrial epithelial cells
Abstract Background There is unmet need for effective therapies of intrauterine adhesions (IUAs) that are common cause of menstrual disturbance and infertility, since current clinical procedures do not improve prognosis for patients with moderate to severe IUA, with a recurrence rate of 23–50%. Stem...
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| Format: | Article |
| Language: | English |
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BMC
2022-05-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-022-02860-w |
| _version_ | 1818191512292294656 |
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| author | Siyu Xia Ming Wu Xinhao Zhou Xiu Zhang Lina Ye Kang Zhang Yiyi Kang Jun Liu Yunci Zhang Wang Wu Dirong Dong Hong Chen Hui Li |
| author_facet | Siyu Xia Ming Wu Xinhao Zhou Xiu Zhang Lina Ye Kang Zhang Yiyi Kang Jun Liu Yunci Zhang Wang Wu Dirong Dong Hong Chen Hui Li |
| author_sort | Siyu Xia |
| collection | DOAJ |
| description | Abstract Background There is unmet need for effective therapies of intrauterine adhesions (IUAs) that are common cause of menstrual disturbance and infertility, since current clinical procedures do not improve prognosis for patients with moderate to severe IUA, with a recurrence rate of 23–50%. Stem cell-based therapy has emerged as a therapeutic option with unsolved issues for IUA patients in the past few years. Primary endometrial epithelial cells for cell therapy are largely hampered with the extremely limited proliferation capacity of uterine epithelial cells. This study was to evaluate whether IUA is curable with conditionally reprogrammed (CR) endometrial epithelial cells. Methods Mouse endometrial epithelial cells (MEECs) were isolated from C57BL female mice, and long-term cultures of MEECs were established and maintained with conditional reprogramming (CR) method. DNA damage response analysis, soft agar assay, and matrigel 3D culture were carried out to determine the normal biological characteristics of CR-MEECs. The tissue-specific differentiation potential of MEECs was analyzed with air–liquid interface (ALI) 3D culture, hematoxylin and eosin (H&E) staining, Masson’s trichrome and DAB staining, immunofluorescence assay. IUA mice were constructed and transplanted with CR-MEECs. Repair and mechanisms of MEECs transplantation in IUA mice were measured with qRT-PCR, Masson’s trichrome, and DAB staining. Results We first successfully established long-term cultures of MEECs using CR approach. CR-MEECs maintained a rapid and stable proliferation in this co-culture system. Our data confirmed that CR-MEECs retained normal biological characteristics and endometrium tissue-specific differentiation potential. CR-MEECs also expressed estrogen and progesterone receptors and maintained the exquisite sensitivity to sex hormones in vitro. Most importantly, allogeneic transplantation of CR-MEECs successfully repaired the injured endometrium and significantly improved the pregnancy rate of IUA mice. Conclusions Conditionally reprogrammed physiological endometrial epithelial cells provide a novel strategy in IUA clinics in a personalized or generalized manner and also serve as a physiological model to explore biology of endometrial epithelial cells and mechanisms of IUA. |
| first_indexed | 2024-12-12T00:15:47Z |
| format | Article |
| id | doaj.art-68702bcd52bf49d5a477b17d5d3b3d72 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-12T00:15:47Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-68702bcd52bf49d5a477b17d5d3b3d722022-12-22T00:44:51ZengBMCStem Cell Research & Therapy1757-65122022-05-0113111510.1186/s13287-022-02860-wTreating intrauterine adhesion using conditionally reprogrammed physiological endometrial epithelial cellsSiyu Xia0Ming Wu1Xinhao Zhou2Xiu Zhang3Lina Ye4Kang Zhang5Yiyi Kang6Jun Liu7Yunci Zhang8Wang Wu9Dirong Dong10Hong Chen11Hui Li12School of Basic Medical Sciences, Wuhan UniversitySchool of Basic Medical Sciences, Wuhan UniversitySchool of Basic Medical Sciences, Wuhan UniversitySchool of Basic Medical Sciences, Wuhan UniversityWuhan University Shenzhen InstituteWuhan University Shenzhen InstituteSchool of Basic Medical Sciences, Wuhan UniversitySchool of Basic Medical Sciences, Wuhan UniversityDepartment of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan UniversityDepartment of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan UniversityDepartment of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan UniversityDepartment of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan UniversitySchool of Basic Medical Sciences, Wuhan UniversityAbstract Background There is unmet need for effective therapies of intrauterine adhesions (IUAs) that are common cause of menstrual disturbance and infertility, since current clinical procedures do not improve prognosis for patients with moderate to severe IUA, with a recurrence rate of 23–50%. Stem cell-based therapy has emerged as a therapeutic option with unsolved issues for IUA patients in the past few years. Primary endometrial epithelial cells for cell therapy are largely hampered with the extremely limited proliferation capacity of uterine epithelial cells. This study was to evaluate whether IUA is curable with conditionally reprogrammed (CR) endometrial epithelial cells. Methods Mouse endometrial epithelial cells (MEECs) were isolated from C57BL female mice, and long-term cultures of MEECs were established and maintained with conditional reprogramming (CR) method. DNA damage response analysis, soft agar assay, and matrigel 3D culture were carried out to determine the normal biological characteristics of CR-MEECs. The tissue-specific differentiation potential of MEECs was analyzed with air–liquid interface (ALI) 3D culture, hematoxylin and eosin (H&E) staining, Masson’s trichrome and DAB staining, immunofluorescence assay. IUA mice were constructed and transplanted with CR-MEECs. Repair and mechanisms of MEECs transplantation in IUA mice were measured with qRT-PCR, Masson’s trichrome, and DAB staining. Results We first successfully established long-term cultures of MEECs using CR approach. CR-MEECs maintained a rapid and stable proliferation in this co-culture system. Our data confirmed that CR-MEECs retained normal biological characteristics and endometrium tissue-specific differentiation potential. CR-MEECs also expressed estrogen and progesterone receptors and maintained the exquisite sensitivity to sex hormones in vitro. Most importantly, allogeneic transplantation of CR-MEECs successfully repaired the injured endometrium and significantly improved the pregnancy rate of IUA mice. Conclusions Conditionally reprogrammed physiological endometrial epithelial cells provide a novel strategy in IUA clinics in a personalized or generalized manner and also serve as a physiological model to explore biology of endometrial epithelial cells and mechanisms of IUA.https://doi.org/10.1186/s13287-022-02860-wMouse endometrial epithelial cells (MEECs)Conditional reprogramming (CR)Intrauterine adhesion (IUA)Regeneration and repairEstrogen/progesterone receptor (ERα/ PR) |
| spellingShingle | Siyu Xia Ming Wu Xinhao Zhou Xiu Zhang Lina Ye Kang Zhang Yiyi Kang Jun Liu Yunci Zhang Wang Wu Dirong Dong Hong Chen Hui Li Treating intrauterine adhesion using conditionally reprogrammed physiological endometrial epithelial cells Stem Cell Research & Therapy Mouse endometrial epithelial cells (MEECs) Conditional reprogramming (CR) Intrauterine adhesion (IUA) Regeneration and repair Estrogen/progesterone receptor (ERα/ PR) |
| title | Treating intrauterine adhesion using conditionally reprogrammed physiological endometrial epithelial cells |
| title_full | Treating intrauterine adhesion using conditionally reprogrammed physiological endometrial epithelial cells |
| title_fullStr | Treating intrauterine adhesion using conditionally reprogrammed physiological endometrial epithelial cells |
| title_full_unstemmed | Treating intrauterine adhesion using conditionally reprogrammed physiological endometrial epithelial cells |
| title_short | Treating intrauterine adhesion using conditionally reprogrammed physiological endometrial epithelial cells |
| title_sort | treating intrauterine adhesion using conditionally reprogrammed physiological endometrial epithelial cells |
| topic | Mouse endometrial epithelial cells (MEECs) Conditional reprogramming (CR) Intrauterine adhesion (IUA) Regeneration and repair Estrogen/progesterone receptor (ERα/ PR) |
| url | https://doi.org/10.1186/s13287-022-02860-w |
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