Characterization of menstrual stem cells: angiogenic effect, migration and hematopoietic stem cell support in comparison with bone marrow mesenchymal stem cells.

Francisca Alcayaga-Miranda,Carolina Aguila-Díaz,Jimena Cuenca,Ainoa Fernandez,Fernando E Figueroa,Patricia Luz-Crawford,Maroun Khoury

doi:10.1186/s13287-015-0013-5

Abstract

IntroductionStem cells isolated from menstrual fluid (MenSCs) exhibit mesenchymal stem cell (MSCs)-like properties including multi-lineage differentiation capacity. Besides, menstrual fluid has important advantages over other sources for the isolation of MSCs, including ease of access and repeated sampling in a noninvasive manner. Such attributes allow the rapid culture of MenSCs in numbers that are sufficient for therapeutical doses, at lower cell passages.MethodsIn this study, we advance the characterization of MenSC populations in comparison to bone marrow derived mesenchymal stem cells (BM-MSCs) with regards to proliferation, lineage differentiation, migration potential, secretion profile and angiogenic properties in vitro and in a matrigel plug assay in mice. We additionally tested their ability to support hematopoietic stem cell (HSC) expansion in vitro.ResultsThe phenotypic analysis of MenSCs revealed a profile largely similar to the BM-MSCs with the exception of a higher expression of the adhesion molecule CD49a (alpha1-integrin). Furthermore, the fibroblast colony forming units (CFU-F) from MenSCs yielded a 2 to 4 fold higher frequency of progenitors and their in vitro migration capacity was superior to BM-MSCs. In addition, MenSCs evidenced a superior paracrine response to hypoxic conditions as evidenced by the secretion of vascular endothelial growth factor and basic fibroblast growth factor and also improved angiogenic effect of conditioned media on endothelial cells. Furthermore, MenSCs were able to induce angiogenesis in a matrigel plug assay in vivo. Thus, an 8-fold increase in hemoglobin content was observed in implanted plugs containing MenSCs compared to BM-MSCs. Finally, we demonstrated, for the first time, the capacity of MenSCs to support the ex-vivo expansion of HSCs, since higher expansion rates of the CD34 + CD133+ population as well as higher numbers of early progenitor (CFU-GEMM) colonies were observed in comparison to the BM source.ConclusionsWe present evidence showing superiority of MenSCs with respect to several functional aspects, in comparison with BM-MSCs. However, the impact of such properties in their use as adult-derived stem cells for regenerative3 medicine remains to be clarified.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0013-5) contains supplementary material, which is available to authorized users.

Highlights

Stem cells isolated from menstrual fluid (MenSCs) exhibit mesenchymal stem cell (MSCs)-like properties including multi-lineage differentiation capacity
We demonstrate that menstrual-derived stem cells (MenSCs) secrete higher amounts of angiogenic factors than bone marrow (BM)-MSCs, resulting in a higher angiogenic potential both in vitro and in vivo
MenSCs exhibit higher proliferation rate, CFU-frequency and migration capacity Multiple in vitro assays were performed to compare distinct properties of MSCs isolated from the menstrual fluid with the gold-standard bone marrow derived mesenchymal stem cells (BM-MSCs)

Summary

Introduction

Stem cells isolated from menstrual fluid (MenSCs) exhibit mesenchymal stem cell (MSCs)-like properties including multi-lineage differentiation capacity. Menstrual fluid has important advantages over other sources for the isolation of MSCs, including ease of access and repeated sampling in a noninvasive manner Such attributes allow the rapid culture of MenSCs in numbers that are sufficient for therapeutical doses, at lower cell passages. Adult stem cells derived from different sources, including bone marrow, adipose tissue or post-natal tissues, such as umbilical cord and placenta, have been shown to possess regenerative, antiinflammatory or immunoregulatory potential in a variety of diseases. The limitation of their clinical use resides in the invasiveness of the extraction methods and in some cases their limited proliferative capacity. Some reports have demonstrated the expression of embryonic markers and pluripotent intracellular cell markers, such as OCT-4, c-kit and SSEA-4, not found on MSCs from other sources, these findings have been disputed, even in cells isolated and cultured under comparable conditions [2,3,4,5,6,7]

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