Autologous cell therapy with CD133+ bone marrow-derived stem cells for refractory Asherman's syndrome and endometrial atrophy: a pilot cohort study

Santamaría, Xavier Alegre; Cabanillas, Sergio; Cervelló, Irene; Arbona, Cristina; Raga, Francisco; Ferro, Jaime; Palmero, Julio; Remohı́, J.; Pellicer, António; Simón, Carlos

doi:10.1093/humrep/dew042

Cited by 262 publications

(238 citation statements)

References 36 publications

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“…Moreover, the collagen/BM-MSC system increased the proliferative abilities of the uterine endometrial and muscular cells, facilitated microvasculature regeneration, and restored the ability of the endometrium to receive an embryo and support its development to a viable stage. 72 Moreover, CD133+ BM-derived stem cell (BMDSC) autologous cell therapy may be useful for the treatment of some pathologies, such as patients with refractory Asherman's syndrome (AS), [73][74][75] which corresponds to a replacement of the endometrial stroma by fibrous tissue and the complete disappearance of the endometrial structure (Donnez and Nisolle, 1994). 74,75 Autologous cell therapy using CD133+ BMDSCs in conjunction with hormonal replacement therapy increased the volume and duration of menses as well as the thickness and angiogenic processes of the endometrium while decreasing the intrauterine adhesion scores within the first three months (Santamaría et al, 2016).…”

Section: Potential Clinical Applications Of Endometrial Mscsmentioning

confidence: 99%

“…72 Moreover, CD133+ BM-derived stem cell (BMDSC) autologous cell therapy may be useful for the treatment of some pathologies, such as patients with refractory Asherman's syndrome (AS), [73][74][75] which corresponds to a replacement of the endometrial stroma by fibrous tissue and the complete disappearance of the endometrial structure (Donnez and Nisolle, 1994). 74,75 Autologous cell therapy using CD133+ BMDSCs in conjunction with hormonal replacement therapy increased the volume and duration of menses as well as the thickness and angiogenic processes of the endometrium while decreasing the intrauterine adhesion scores within the first three months (Santamaría et al, 2016). 73,75 Furthermore, BMDSC transplantation in a murine model of Asherman's syndrome improved fertility in the mice, demonstrating a functional role for these cells in uterine repair.…”

Section: Potential Clinical Applications Of Endometrial Mscsmentioning

confidence: 99%

“…74,75 Autologous cell therapy using CD133+ BMDSCs in conjunction with hormonal replacement therapy increased the volume and duration of menses as well as the thickness and angiogenic processes of the endometrium while decreasing the intrauterine adhesion scores within the first three months (Santamaría et al, 2016). 73,75 Furthermore, BMDSC transplantation in a murine model of Asherman's syndrome improved fertility in the mice, demonstrating a functional role for these cells in uterine repair. 76 Many reproductive alterations are associated with abnormal endometrial proliferation; therefore, endometrial MSCs may perform an important role in the physiopathology of diseases, including human endometriosis, adenomyosis, and infertility problems related to hypoplasia or endometrial atrophy, 53 and probably in some important diseases within veterinary medicine, such as cystic endometrial hyperplasia in dogs, equine endometriosis and endometrial cancer.…”

Section: Potential Clinical Applications Of Endometrial Mscsmentioning

confidence: 99%

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The endometrium as a source of mesenchymal stem cells in domestic animals and possible applications in veterinary medicine

2017

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Mesenchymal stem cells (MSCs) have been isolated from the endometrium of humans, mice, cows, pigs and ewes. Typically, these cells are detected in the deep regions of the endometrium, closer to the union with the myometrium. MSCs possess characteristics such as clonogenicity and multipotentiality since they can differentiate in vitro into adipogenic, chondrogenic and osteogenic lineages. These cells can be induced to differentiate in vitro not only into the mesodermal lineage but also into the endodermal and ectodermal lineages. Therefore, MSCs show a great regenerative capacity for various organs and tissues, including the endometrium. Some advantages of endometrial MSCs compared with other MSC sources are their immune modulating activity, their ease of obtainment, and the amount of sample that may be collected. The study of endometrial MSCs in domestic animals is a new and promising field because increasing our understanding of the physiology and biology of these cells may lead to a better understanding of the physiopathology of reproductive diseases, and the development of treatment methods for infertility problems. In other veterinary medicine fields, MSCs can be used for the treatment of autoimmune diseases, cardiac affections, musculoskeletal and articular lesions, muscle degeneration, type 1 diabetes, urinary tract diseases, neurodegenerative processes and tumours. Finally, MSCs are also an important clinical tool for tissue engineering and regenerative medicine. The aim of this review is to present an updated outlook of the knowledge regarding endometrial MSCs and their possible applications in veterinary medicine.

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Section: Potential Clinical Applications Of Endometrial Mscsmentioning

confidence: 99%

Section: Potential Clinical Applications Of Endometrial Mscsmentioning

confidence: 99%

Section: Potential Clinical Applications Of Endometrial Mscsmentioning

confidence: 99%

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The endometrium as a source of mesenchymal stem cells in domestic animals and possible applications in veterinary medicine

2017

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“…This great finding leads to the initiation of BM-MSC-based therapy for AS. Despite the mechanism is not clear, BM-MSCs-therapy did improve endometrial regeneration in severe AS, showing enhanced-thickness of endometrium (Nagori et al, 2011;Singh et al, 2014) and two living births in a recent report (Santamaria et al, 2016). Therefore, we are interested in the existence and stemness alterations of endometrial intrinsic progenitors/stem cells, the interaction between endometrial intrinsic progenitors/stem cells and BM-MSCs in AS and the molecular mechanisms spanning the principle pathogenesis of AS.…”

Section: Introductionmentioning

confidence: 99%

Transplantation of collagen scaffold with autologous bone marrow mononuclear cells promotes functional endometrium reconstruction via downregulating ΔNp63 expression in Asherman’s syndrome

Zhao

Cao

Zhu

et al. 2016

Sci. China Life Sci.

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Asherman's syndrome (AS) is a common disease that presents endometrial regeneration disorder. However, little is known about its molecular features of this aregenerative endometrium in AS and how to reconstruct the functioning endometrium for the patients with AS. Here, we report that ΔNp63 is significantly upregulated in residual epithelial cells of the impaired endometrium in AS; the upregulated-ΔNp63 induces endometrial quiescence and alteration of stemness. Importantly, we demonstrate that engrafting high density of autologous bone marrow mononuclear cells (BMNCs) loaded in collagen scaffold onto the uterine lining of patients with AS downregulates ΔNp63 expression, reverses ΔNp63-induced pathological changes, normalizes the stemness alterations and restores endometrial regeneration. Finally, five patients achieved successful pregnancies and live births. Therefore, we conclude that ΔNp63 is a crucial therapeutic target for AS. This novel treatment significantly improves the outcome for the patients with severe AS.Asherman's syndrome, ΔNp63, quiescence, endometrial regeneration, bone marrow stem cell based therapy Citation:

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“…After transplantation, BMSCs can migrate and accumulate in endometrial tissue. A clinical research also implicated that intrauterine transplantation of autologous bone marrow derived mesenchymal stem cells were beneficial for the regeneration of injured endometrium [7]. However, the specific mechanism still requires further investigation [8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Application of Bone Marrow-Derived Mesenchymal Stem Cells in the Treatment of Intrauterine Adhesions in Rats

Wang

Ju²,

Pan³

et al. 2016

Cell Physiol Biochem

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Aims: To investigate the therapeutic effects of bone marrow-derived mesenchymal stem cells (BMSCs) transplantation on intrauterine adhesions (IUA). Methods: BMSCs were isolated and labeled by green fluorescence protein. IUA model was established by mechanical injury. 48 rats were randomly divided into control, IUA model, BMSCs vein injection and BMSCs intrauterine injection groups (n=12 in each group). The third generation of BMSCs was injected through tail vein or intrauterine. Three rats were killed at time 0 h, 7 d, 14 d and 28 d and bilateral uterus were obtained at each time points for the subseqent experiments. Morphological changes were determined by hematoxylin-eosin staining or Masson staining. Estrogen receptor (ER) and progesterone receptor (PR) were detected by immunohistochemistry. Results: BMSCs were specifically stained by CD44 and CD90, but not by CD45. Before treatment, the numbers of endometrial glands were significantly decreased, while fibrosis area rate was increased in IUA model group (P<0.05 vs Control). Meanwhile, ER expression, but not PR was significantly up-regulated in model group (P<0.05 vs Control). By contrast, the therapies by BMSCs transplantation through either tail vein injection or intrauterine injection significantly elevated the numbers of endometrial glands and decreased the fibrosis area rate (P<0.05 vs Model). Moreover, both ER and PR were remarkably up-regulated after BMSCs transplantation (P<0.05 vs Model). The therapeutic effect attained to optimal level 1 or 2 weeks after transplantation. Conclusion: BMSCs transplantation was effective to repair the damaged endometrium likely through promoting the ER and PR expressions.

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Autologous cell therapy with CD133+ bone marrow-derived stem cells for refractory Asherman's syndrome and endometrial atrophy: a pilot cohort study

Abstract: This study was registered with ClinicalTrials.gov (NCT02144987).

Cited by 262 publications

References 36 publications

The endometrium as a source of mesenchymal stem cells in domestic animals and possible applications in veterinary medicine

The endometrium as a source of mesenchymal stem cells in domestic animals and possible applications in veterinary medicine

Transplantation of collagen scaffold with autologous bone marrow mononuclear cells promotes functional endometrium reconstruction via downregulating ΔNp63 expression in Asherman’s syndrome

Application of Bone Marrow-Derived Mesenchymal Stem Cells in the Treatment of Intrauterine Adhesions in Rats

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