The Bone Marrow-Derived Human Mesenchymal Stem Cell: Potential Progenitor of the Endometrial Stromal Fibroblast1

Abstract

The cellular sources that contribute to the renewal of human endometrium are largely unknown. It has been suggested that endometrial stem cells originate from bone marrow-derived mesenchymal stem cells (MSC), with subsequent development into endometrial stromal fibroblasts (hESF). We hypothesized that if bone marrow-derived MSC contribute to endometrial regeneration and are progenitors of hESF, their treatment with agents known to regulate hESF differentiation could promote their differentiation down the stromal fibroblast lineage. To this end, we treated bone marrow-derived MSC with estradiol and progesterone, bone morphogenetic protein 2 (BMP2), and activators of the protein kinase A (PKA) pathway and investigated specific markers of hESF differentiation (decidualization). Furthermore, we investigated the transcriptome of these cells in response to cAMP and compared this to the transcriptome of hESF decidualized in response to activation of the PKA pathway. The data support the idea that MSC can be differentiated down the hESF pathway, as evidenced by changes in cell shape and common expression of decidual markers and other genes important in hESF differentiation and function, and that bone marrow-derived MSC may be a source of endometrial stem/progenitor cells. In addition, we identified MSC-specific markers that distinguish them from other fibroblasts and, in particular, from hESF, which is of biologic relevance and practical value to the field of endometrial stem cell research.

Role of the Urokinase-Fibrinolytic System in Epithelial–Mesenchymal Transition during Lung Injury

“…The literature suggests that myofibroblasts arise from activation of resident lung fibroblasts, from differentiation of bone-marrowederived stromal cells and also from ATII cells via EMT. 1,37,38 Other reports suggest increased expression of mesenchymal marker proteins and mRNAs by hyperplastic ATII cells in human IPF lungs 4 and that approximately 30% to 50% of fibroblasts are also derived via EMT in BLM-induced lung injury. 11 This supports the importance of transformation of ATII cells into myofibroblasts via EMT in the pathogenesis of PF 12 in addition to apoptosis of ATII cells.…”

Exploring the Human Term Placenta as a Novel Source for Stem Cells and their Application in the Clinic

“…Thus, they may be a superior MSC source for clinical trials than the traditional source which is adult bone marrow. This section will focus on the isolation of MSC from amniotic fluid (Mareschi et al, 2009, Nadri and Soleimani, 2007, Roubelakis et al, 2007, the amniotic membrane (Soncini et al, 2007, Portmann-Lanz et al, 2006, Diaz-Prado et al, 2010, the chorion (chorion laeve and chorionic villi) (Soncini et al, 2007, Portmann-Lanz et al, 2006, Igura et al, 2004, Poloni et al, 2008, the decidua (Macias et al, 2010, Aghajanova et al, 2010, umbilical cord/Wharton's jelly (Mitchell et al, 2003, Reinisch et al, 2007, Petsa et al, 2009) and umbilical cord blood (Mareschi et al, 2001, Bieback et al, 2004, Romanov et al, 2003. This section will also discuss the isolation of haematopoietic stem cells from the umbilical cord blood and the application of these cells.…”

Endometrial reconstruction from stem cells

“…This was confirmed in mouse bone marrow transplant studies (reviewed in Gargett and Masuda (6) and Du and Taylor (43)) and in a human study of female recipients of male donor bone marrow transplants, in which male XY þ endometrial cells were identified in the non-SP rather than SP cells (47). However, human bone marrow-derived MSC can differentiate into decidualized endometrial stromal fibroblasts in vitro as shown by gene profiling (51).…”