Cell-based endometrial regeneration: current status and future perspectives

Keyhanvar, Neda; Zarghami, Nosratollah; Bleisinger, Nathalie; Hajipour, Hamed; Fattahi, Amir; Nouri, Mohammad; Dittrich, Ralf

doi:10.1007/s00441-021-03419-6

Cited by 14 publications

(10 citation statements)

References 114 publications

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“…MSCs from multiple sources, including WJ-MSCs, have been shown to facilitate endometrial regeneration and fertility restoration in rat and rhesus monkey intrauterine adhesions (IUA) models, primarily due to their paracrine effects at the lesion site [41][42][43][44][45] . To further test the therapeutic potential of WJ-MSCs (MSD) for tissue regeneration, we established a rat IUA model and transplanted WJ-MSCs generated by M6 and MSD into the uterus of the rats.…”

Section: Development Of "Mince-soak-digest (Msd)" Methodsmentioning

confidence: 99%

A Robust and Highly Efficient Approach for Isolation of Mesenchymal Stem Cells from Wharton’s Jelly for Tissue Repair

Zheng

Gao²,

Chen

et al. 2021

Preprint

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BackgroundMesenchymal stem cells (MSCs) derived from umbilical cord Wharton’s Jelly (WJ-MSCs) are emerging as promising therapeutics for a variety of diseases due to their ability of regeneration and immunomodulation and their non-tumorigenic and non-immunogenic properties. Although multiple protocols have been developed for WJ-MSCs isolation, insufficient cell numbers, heterogeneous cell population, and variations in procedures between different laboratories impede further clinical applications.MethodsWe compared six widely used WJ-MSCs isolation methods regarding cell morphology, yield, purity, proliferation rate, and differentiation potential. Based on these analyses, we developed a new isolation approach called “Mince-Soak-Digest (MSD)”, and compared its efficiency with the existing methods. Furthermore, we transplanted WJ-MSCs isolated by different methods to the rat uterus to test their ability for tissue repair.ResultsBased on the comparison and analysis of the six widely used isolation protocols, we identified that the inefficiency of the digestion of the extracellular matrix results in low cell yield. Thus, we have developed a robust and highly efficient method to isolate MSCs from WJ by incorporating a soaking step to facilitate the digestion of the extracellular matrix and release of the cells. Our newly developed method generates significantly higher cell yield (4 to 10-fold higher) than six widely used methods that we tested with high purity and consistency. Importantly, by transplantation of WJ-MSCs isolated by MSD to the rat uterus, we repair the endometrial injury and restore the fertility of the rats.ConclusionOur results provide a robust and highly efficient approach for isolating WJ-MSCs to restore injured tissue. The higher efficiency of MSD assures the abundance of WJ-MSCs for clinical applications. Furthermore, the reliability of MSD contributes to the standardization of WJ-MSCs isolation, which eliminates the discrepancies due to isolation procedures, thus facilitates the evaluation of the efficacy of WJ-MSCs across various human clinical applications.

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Section: Development Of "Mince-soak-digest (Msd)" Methodsmentioning

confidence: 99%

A Robust and Highly Efficient Approach for Isolation of Mesenchymal Stem Cells from Wharton’s Jelly for Tissue Repair

Zheng

Gao²,

Chen

et al. 2021

Preprint

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“…The introduction of various biological substances that stimulate tissue regeneration can promote endometrial injury repair ( Cervelló et al, 2015 ; Almeida et al, 2021 ; Ma et al, 2021 ). Stem cell therapy is currently the most attractive therapeutic approach to repairing endometrial damage ( Keyhanvar et al, 2021 ; Gharibeh et al, 2022 ). Among them, endometrial mesenchymal stem/progenitor cells (eMSC), a highly proliferative class of cells derived from the dynamic, cyclically regenerating human endometrium, show promise in regenerative medicine through paracrine immunomodulatory effects and enhancing endogenous stem cell function ( Hennes et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…It is worth mentioning that it is difficult to make practical recommendations for the clinical treatment of human endometrium-related diseases due to the diversity of animal models, the limited number of studies, and the uniqueness of the endometrium. Other than that, research on endometrial regeneration based on stem cells or growth factors is in its infancy, and the ethical and technical issues involved in the context of human studies make it a long way to go ( Keyhanvar et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Recent Developments in Biomaterial-Based Hydrogel as the Delivery System for Repairing Endometrial Injury

Cai

Hou

Sun

et al. 2022

Front. Bioeng. Biotechnol.

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Endometrial injury caused by intrauterine surgery often leads to pathophysiological changes in the intrauterine environment, resulting in infertility in women of childbearing age. However, clinical treatment strategies, especially for moderate to severe injuries, often fail to provide satisfactory therapeutic effects and pregnancy outcomes. With the development of reproductive medicine and materials engineering, researchers have developed bioactive hydrogel materials, which can be used as a physical anti-adhesion barrier alone or as functional delivery systems for intrauterine injury treatment by loading stem cells or various active substances. Studies have demonstrated that the biomaterial-based hydrogel delivery system can provide sufficient mechanical support and improve the intrauterine microenvironment, enhance the delivery efficiency of therapeutic agents, prolong intrauterine retention time, and perform efficiently targeted repair compared with ordinary drug therapy or stem cell therapy. It shows the promising application prospects of the hydrogel delivery system in reproductive medicine. Herein, we review the recent advances in endometrial repair methods, focusing on the current application status of biomaterial-based hydrogel delivery systems in intrauterine injury repair, including preparation principles, therapeutic efficacy, repair mechanisms, and current limitations and development perspectives.

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“…Owing to the easy isolation from various tissues and the properties of self-renewal, multipotency, and immunomodulation, MSC-based therapy has become a promising method for the thin endometrium. Mesenchymal stem cells (MSCs) have been used to treat the thin endometrium of patients with Asherman syndrome and improve reproductive outcomes ( Azizi et al, 2018 ; Gao et al, 2019; Keyhanvar et al, 2021 ). Varied delivery ways were used in MSC perfusion.…”

Section: Introductionmentioning

confidence: 99%

Regenerative Effects of Locally or Intra-Arterially Administered BMSCs on the Thin Endometrium

Guo

Chang

et al. 2022

Front. Bioeng. Biotechnol.

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Stem cell–based therapy plays a pivotal role in the regeneration of damaged endometrium. Previous studies have demonstrated the therapeutic potential of bone marrow mesenchymal stem cells (BMSCs) through diverse administration ways. However, the homing, survival, and differentiation potential of these differently administered BMSCs are poorly defined, and the best route of administration is not well-defined. Herein, we aim to compare the engraftment, retaining time, and therapeutic efficiency of differently administered BMSCs. To achieve this, GFP/Luc-labeled BMSCs administered in two modes were assessed in a thin endometrium rat model: either into the damaged horns directly or through the ipsilateral iliac artery. The retaining time and hemi-quantitative distribution were evaluated by in vivo bioluminescence imaging and immunohistological analysis. Locally administered BMSCs were strongly detected in the abdomen at the first 4 days post treatment but underwent a rapid decrease in luminescent signal afterward and were rarely found 28 days after treatment. In contrast, the retaining time of BMSCs injected through the iliac artery was longer, reflected by more GFP-positive cells detected in the uterine section 28 days post treatment. Differentiation toward endometrial stromal cells was observed. Both routes of administration contributed to the restoration of the damaged endometrium, showing a comparable increase in the endometrial thickness and a decrease in fibrosis. However, more importantly, higher expression of LIF and VEGF, better recruitment, and longer retainment were found in the intra-arterial administration, contributing to the establishment of the optimal administration mode in clinical practice.

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Cell-based endometrial regeneration: current status and future perspectives

Cited by 14 publications

References 114 publications

A Robust and Highly Efficient Approach for Isolation of Mesenchymal Stem Cells from Wharton’s Jelly for Tissue Repair

A Robust and Highly Efficient Approach for Isolation of Mesenchymal Stem Cells from Wharton’s Jelly for Tissue Repair

Recent Developments in Biomaterial-Based Hydrogel as the Delivery System for Repairing Endometrial Injury

Regenerative Effects of Locally or Intra-Arterially Administered BMSCs on the Thin Endometrium

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