Comparison of CD146 +/− mesenchymal stem cells in improving premature ovarian failure

Abstract Background Mesenchymal stem cells (MSCs) are a heterogeneous group of subpopulations with differentially expressed surface markers. CD146 + MSCs correlate with high therapeutic and secretory potency. However, their therapeutic efficacy and mechanisms in premature ovarian failure (POF) have...

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Main Authors: Lin Zhang, Yang Sun, Xiao-Xu Zhang, Yu-Bin Liu, Hui-Yan Sun, Chu-Tse Wu, Feng-Jun Xiao, Li-Sheng Wang
Format: Article
Language:English
Published: BMC 2022-06-01
Series:Stem Cell Research & Therapy
Subjects:
Online Access:https://doi.org/10.1186/s13287-022-02916-x
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author Lin Zhang
Yang Sun
Xiao-Xu Zhang
Yu-Bin Liu
Hui-Yan Sun
Chu-Tse Wu
Feng-Jun Xiao
Li-Sheng Wang
author_facet Lin Zhang
Yang Sun
Xiao-Xu Zhang
Yu-Bin Liu
Hui-Yan Sun
Chu-Tse Wu
Feng-Jun Xiao
Li-Sheng Wang
author_sort Lin Zhang
collection DOAJ
description Abstract Background Mesenchymal stem cells (MSCs) are a heterogeneous group of subpopulations with differentially expressed surface markers. CD146 + MSCs correlate with high therapeutic and secretory potency. However, their therapeutic efficacy and mechanisms in premature ovarian failure (POF) have not been explored. Methods The umbilical cord (UC)-derived CD146 +/− MSCs were sorted using magnetic beads. The proliferation of MSCs was assayed by dye670 staining and flow cytometry. A mouse POF model was established by injection of cyclophosphamide and busulfan, followed by treatment with CD146 +/− MSCs. The therapeutic effect of CD146 +/− MSCs was evaluated based on body weight, hormone levels, follicle count and reproductive ability. Differential gene expression was identified by mRNA sequencing and validated by RT-PCR. The lymphocyte percentage was detected by flow cytometry. Results CD146 +/− MSCs had similar morphology and surface marker expression. However, CD146 + MSCs exhibited a significantly stronger proliferation ability. Gene profiles revealed that CD146 + MSCs had a lower levels of immunoregulatory factor expression. CD146 + MSCs exhibited a stronger ability to inhibit T cell proliferation. CD146 +/− MSCs treatment markedly restored FSH and E2 hormone secretion level, reduced follicular atresia, and increased sinus follicle numbers in a mouse POF model. The recovery function of CD146 + MSCs in a reproductive assay was slightly improved than that of CD146 - MSCs. Ovary mRNA sequencing data indicated that UC-MSCs therapy improved ovarian endocrine locally, which was through PPAR and cholesterol metabolism pathways. The percentages of CD3, CD4, and CD8 lymphocytes were significantly reduced in the POF group compared to the control group. CD146 + MSCs treatment significantly reversed the changes in lymphocyte percentages. Meanwhile, CD146 - MSCs could not improve the decrease in CD4/8 ratio induced by chemotherapy. Conclusion UC-MSCs therapy improved premature ovarian failure significantly. CD146 +/− MSCs both had similar therapeutic effects in repairing reproductive ability. CD146 + MSCs had advantages in modulating immunology and cell proliferation characteristics.
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spelling doaj.art-cc8dea509ae4415a9e8b08343f24dd2e2022-12-22T00:17:10ZengBMCStem Cell Research & Therapy1757-65122022-06-0113111610.1186/s13287-022-02916-xComparison of CD146 +/− mesenchymal stem cells in improving premature ovarian failureLin Zhang0Yang Sun1Xiao-Xu Zhang2Yu-Bin Liu3Hui-Yan Sun4Chu-Tse Wu5Feng-Jun Xiao6Li-Sheng Wang7Beijing Institute of Radiation MedicineLaboratory of Molecular Diagnosis and Regenerative Medicine, Medical Research Center, The Affiliate Hospital of Qingdao UniversityLaboratory of Molecular Diagnosis and Regenerative Medicine, Medical Research Center, The Affiliate Hospital of Qingdao UniversityBeijing Institute of Radiation MedicineYanda Medical Research Institute, Hebei Yanda HospitalBeijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineLaboratory of Molecular Diagnosis and Regenerative Medicine, Medical Research Center, The Affiliate Hospital of Qingdao UniversityAbstract Background Mesenchymal stem cells (MSCs) are a heterogeneous group of subpopulations with differentially expressed surface markers. CD146 + MSCs correlate with high therapeutic and secretory potency. However, their therapeutic efficacy and mechanisms in premature ovarian failure (POF) have not been explored. Methods The umbilical cord (UC)-derived CD146 +/− MSCs were sorted using magnetic beads. The proliferation of MSCs was assayed by dye670 staining and flow cytometry. A mouse POF model was established by injection of cyclophosphamide and busulfan, followed by treatment with CD146 +/− MSCs. The therapeutic effect of CD146 +/− MSCs was evaluated based on body weight, hormone levels, follicle count and reproductive ability. Differential gene expression was identified by mRNA sequencing and validated by RT-PCR. The lymphocyte percentage was detected by flow cytometry. Results CD146 +/− MSCs had similar morphology and surface marker expression. However, CD146 + MSCs exhibited a significantly stronger proliferation ability. Gene profiles revealed that CD146 + MSCs had a lower levels of immunoregulatory factor expression. CD146 + MSCs exhibited a stronger ability to inhibit T cell proliferation. CD146 +/− MSCs treatment markedly restored FSH and E2 hormone secretion level, reduced follicular atresia, and increased sinus follicle numbers in a mouse POF model. The recovery function of CD146 + MSCs in a reproductive assay was slightly improved than that of CD146 - MSCs. Ovary mRNA sequencing data indicated that UC-MSCs therapy improved ovarian endocrine locally, which was through PPAR and cholesterol metabolism pathways. The percentages of CD3, CD4, and CD8 lymphocytes were significantly reduced in the POF group compared to the control group. CD146 + MSCs treatment significantly reversed the changes in lymphocyte percentages. Meanwhile, CD146 - MSCs could not improve the decrease in CD4/8 ratio induced by chemotherapy. Conclusion UC-MSCs therapy improved premature ovarian failure significantly. CD146 +/− MSCs both had similar therapeutic effects in repairing reproductive ability. CD146 + MSCs had advantages in modulating immunology and cell proliferation characteristics.https://doi.org/10.1186/s13287-022-02916-xUC-CD146 +/− MSCsPOFImmune regulation
spellingShingle Lin Zhang
Yang Sun
Xiao-Xu Zhang
Yu-Bin Liu
Hui-Yan Sun
Chu-Tse Wu
Feng-Jun Xiao
Li-Sheng Wang
Comparison of CD146 +/− mesenchymal stem cells in improving premature ovarian failure
Stem Cell Research & Therapy
UC-CD146 +/− MSCs
POF
Immune regulation
title Comparison of CD146 +/− mesenchymal stem cells in improving premature ovarian failure
title_full Comparison of CD146 +/− mesenchymal stem cells in improving premature ovarian failure
title_fullStr Comparison of CD146 +/− mesenchymal stem cells in improving premature ovarian failure
title_full_unstemmed Comparison of CD146 +/− mesenchymal stem cells in improving premature ovarian failure
title_short Comparison of CD146 +/− mesenchymal stem cells in improving premature ovarian failure
title_sort comparison of cd146 mesenchymal stem cells in improving premature ovarian failure
topic UC-CD146 +/− MSCs
POF
Immune regulation
url https://doi.org/10.1186/s13287-022-02916-x
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