Woof Woof – Bone marrow cells are coming

Do multipotent cells promote endometriosis?

Key Points

Highlight:

• Bone marrow-derived stem cells can engraft endometriotic lesion and associate with the lesion growth without themselves replicating. This study examined how BMDCs affect endometriosis growth.

Importance:

• Endometrial cells undergo proliferation when co-cultured with bone marrow-derived stem cells, suggesting that stem cell-derived factors influence the growth of endometriotic lesions.

What has been done:

• Study participants were recruited from the reproductive endocrinology practice at the Yale School of Medicine.
• Control cases (n=20) were women with benign disease, and test cases were women with moderate-to-severe endometriosis, stages III, and IV (n=20).
• Primary eutopic endometrial stromal or endometriosis derived cells were isolated and co-cultured with bone marrow-derived stem cells.
• The effect of BMSCs on endometriosis gene and protein expression were evaluated.

Results:  

• BMDCs enhanced cell proliferation in endometriosis.
• BMDCs increased Cyclin-dependent kinase 1 (CDK1) levels in endometriosis cells and in vivo endometriotic lesions.

Limitation:

• The study used eutopic endometrial stromal cells instead of primary ectopic endometrial stromal cells which are more relevant, but difficult to grow.

Lay Summary

Bone marrow contains cells that can travel to multiple organ sites and differentiate into specific tissue cells. Bone marrow-derived stem cells have also been associated with the pathogenesis of endometriosis. These cells can affect epithelial and stromal cell regeneration both in eutopic endometrial tissue and endometriosis. However, how bone marrow-derived stem cell engraftment alters the endometrial-cell behavior is still poorly understood.

This study by Chen et al. from the Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, CT, USA investigated the effect of co-culturing endometrial cells with bone marrow-derived stem cells. Furthermore, the authors examined three cell signaling pathways to better understand the underlying mechanisms. The study results were recently published in "Reproductive Sciences".

Recruited study subjects were women with and without endometriosis from the reproductive endocrinology practice at the Yale School of Medicine. Specifically, the control group (n=20) were women who underwent surgery for other benign diseases than endometriosis; and study subjects were women with moderate-to-severe endometriosis (stages III and IV). The authors carried out co-culture experiments whereby endometrial stromal cells from these subjects were cultured together with bone marrow-derived stem cells. After this, the effects of bone marrow-derived stem cells were examined through analyzing differentially expressed molecules that are involved in cell signaling pathways.

The results demonstrate that the co-culturing system increased endometrial stromal cell proliferation. At the same time, bone marrow-derived stem cells increased Cyclin-dependent kinase 1 molecule expression in endometriosis cell line and primary endometrial stromal cells derived from women with endometriosis. This effect was not seen in endometrial cells from control women. Furthermore, studies using a mouse model of endometriosis again showed an increased CDK1 expression associated with bone marrow-derived stem cell engraftment. 

Cyclin-dependent kinase 1 is a kinase that plays a crucial role in cell cycle regulation. The results of this study suggest that bone marrow-derived stem cells may be a critical factor that can markedly affect endometriosis growth by regulating the cell cycle and cell proliferation. Therefore, more future work on BMDCs in endometriosis may be required to generate new targets and therapy that can control endometriosis.

Research Source: https://pubmed.ncbi.nlm.nih.gov/32812213/