Cellular therapies for the endometrium: An update

Queckbörner, Suzanna; Davies, Lindsay C.; Grothusen, Carolina von; Santamaría, Xavier Alegre; Simón, Carlos; Danielsson, Kristina Gemzell

doi:10.1111/aogs.13598

Cited by 22 publications

(12 citation statements)

References 44 publications

(91 reference statements)

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“…Cell therapy has been a steadily expanding field with 327 active clinical trials, registered with clinicaltrials.gov (as of October 28, 2019), involving “mesenchymal cells.” These cell products have been primarily developed to alleviate diseases with pro-inflammatory components, or a need to repair damaged tissue. This growing trend towards cell therapeutics has now been proposed and piloted for endometrial restoration [19–23].…”

Section: Introductionmentioning

confidence: 99%

“…In the last 10 years, stromal cells derived from menstrual blood (menSCs) and umbilical cord (UC MSCs) have been piloted as a cell therapy for infertility and AS (reviewed [23]). These pilot studies have provided promising results, with increased endometrial thickness (an established measurement of responsiveness to therapy) and temporarily resumed menstruation [21, 24].…”

Section: Introductionmentioning

confidence: 99%

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Endometrial stromal cells exhibit a distinct phenotypic and immunomodulatory profile

et al. 2020

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BackgroundIn Asherman’s syndrome (AS), intrauterine scarring and fibrotic adhesions lead to menstrual disorders, pregnancy loss, or infertility. A few clinical trials have piloted cell therapy to overcome AS. Understanding the role of the stromal compartment in endometrial regeneration remains poorly understood. We hypothesize that endometrial stromal cells (eSCs) represent a relevant cell population to establish novel cell-based therapeutics for endometrial disorders. The aim of this study was to characterize eSCs and evaluate their immune-cell interactions.MethodseSCs were isolated from healthy donors, during the proliferative stage of the menstrual cycle. Cells were characterized for expression of mesenchymal stromal cell (MSC) markers and assessed for their tumorigenic potential. eSCs were co-cultured with interferon γ and tumor necrosis factor α, and cell surface expression of their respective receptors and human leukocyte antigen (HLA) I and II determined by flow cytometry. Secreted levels of key immunomodulatory factors were established. eSCs were cultured with activated peripheral blood mononuclear cells, and T cell differentiation and proliferation determined.ResultseSCs demonstrated an MSC surface phenotype and exhibited multipotency. Expanded eSCs retained chromosomal stability and demonstrated no tumorigenicity. Upon stimulation, eSCs licensed to an anti-inflammatory phenotype with upregulated secretion of immunomodulatory factors. Stimulated eSCs did not express HLA class II. eSCs suppressed the proliferation and activation of CD4+ T cells, with the eSC secretome further downregulating central memory T cells and upregulating effector memory (EM) cells.ConclusionsDifferential responsiveness to inflammation by eSCs, compared to other MSC sources, demonstrates the need to understand the specific functional effects of individual stromal cell sources. A lack of HLA class II and triggering of EM T cell differentiation strongly links to innate in vivo roles of eSCs in tissue repair and immune tolerance during pregnancy. We conclude that eSCs may be an ideal cell therapy candidate for endometrial disorders.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Endometrial stromal cells exhibit a distinct phenotypic and immunomodulatory profile

et al. 2020

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“…Multiple studies show that the stem cells may improve the outcomes of injuring diseases [17] [18], but it is still unclear that whether stem cells transplantation can be used as a therapy for IUAs. Nesrine [19] et al Investigated the Transforming Growth Factors-β (TGF-β), Tumor Necrosis Factor-α (TNF-α) and Vascular Endothelial Growth Factor (VEGF) are significant decreased in extracellular vesicles derived from human umbilical cord mesenchymal stem cells (UCMSCs-EVs) alone or combined with estrogen therapeutic groups.…”

Section: Molecular Experiments For Stem Cell and Iuasmentioning

confidence: 99%

Intrauterine Adhesions (IUAs) or Asherman’s Syndrome (AS) and the Stem Cells Treatment: A Systemic Review and Meta-Analysis

Zhang¹,

Mao²,

Zhao³

et al. 2021

JBM

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Background: Intrauterine Adhesions (IUAs) or Asherman's Syndrome (AS) usually contains symptoms such as decreased menstrual flow or even amenorrhea, chronic pelvic pain, recurrent abortion and infertility. The current treatment of IUAs includes hysteroscopic adhesiolysis, oral hormone and biological barriers, but each of them has limitation. Stem cell therapy may be an expanding field seeking for therapy in IUAs. Objective: We will discuss current advances in stem cell therapy as a treatment for endometrial pathophysiology. Materials and Methods: We search on PubMed, Embase and Cochrane library and select several keywords on researches, then review the cell biology theories and animal experiments, finally do meta-analysis in human clinical trials. Results: 77 articles on PubMed, 71 articles on Embase and 17 articles on Cochrane Library, as a result, 37 articles are included under the criteria, which are intrauterine adhesions (IUAs), Asherman's Syndrome (AS), cell therapy, stem cells, bone marrow stem cells, clinical trials, recent 10 years and human or animal experiments. The included criteria: original articles, cohort study, case control study, animal experiments, human clinical trials, high quality, 10 years recent. The excluded articles are case reports, meeting reports, low quality or more than 10 years ago. Conclusion: Stem cell may be a new therapeutic schedule for IUAs in the future clinical treatment, but it is necessary to compare it with traditional therapy such as oral hormone, also the development of random clinical tests should proceed. For clinical treatment on IUAs, stem cells could be a new choice.

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“…In type IIIb IUAs, the very poor results obtained with hysteroscopic surgery impel us to seek alternatives to regenerate the inadequate endometrium with the help of cell-based therapies using endometrial stem/progenitor cells (14,(90)(91)(92).…”

Section: Tablementioning

confidence: 99%

Should we consider alternative therapies to operative hysteroscopy for the treatment of Asherman syndrome?

Santamaría

Liu

Aghajanova

et al. 2020

Fertility and Sterility

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Cellular therapies for the endometrium: An update

Cited by 22 publications

References 44 publications

Endometrial stromal cells exhibit a distinct phenotypic and immunomodulatory profile

Endometrial stromal cells exhibit a distinct phenotypic and immunomodulatory profile

Intrauterine Adhesions (IUAs) or Asherman’s Syndrome (AS) and the Stem Cells Treatment: A Systemic Review and Meta-Analysis

Should we consider alternative therapies to operative hysteroscopy for the treatment of Asherman syndrome?

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