A Mesoderm-Derived Precursor for Mesenchymal Stem and Endothelial Cells

Abstract

Summary Among the three embryonic germ layers, the mesoderm is a major source of the mesenchymal precursors giving rise to skeletal and connective tissues. These precursors, however, have not been previously identified and characterized. Using human embryonic stem cells directed to mesendodermal differentiation, here we show that mesenchymal stem/stromal cells (MSCs) originate from a population of mesodermal cells identified by expression of the apelin receptor. In semisolid medium, these precursors form FGF2-dependent compact spheroid colonies containing mesenchymal cells with a transcriptional profile representative of mesoderm-derived embryonic mesenchyme. When transferred to the adherent cultures, individual colonies give rise to MSC lines with chondro-, osteo-, and adipogenenic differentiation potentials. Although the MSC lines lacked endothelial potential, endothelial cells could be derived from mesenchymal colonies, suggesting that, similar to hematopoietic cells, MSCs arise from precursors with angiogenic potential. Together, these studies identified a common precursor of mesenchymal and endothelial cells, mesenchymoangioblast, as the source of mesoderm-derived MSCs.

Murine Spleen Tissue Regeneration from Neonatal Spleen Capsule Requires Lymphotoxin Priming of Stromal Cells

“…Indeed, LN CD31 + endothelial cells have now been recognized as a critical component for tissue formation in an LTbR-dependent manner (29). Early mesenchymoangioblasts derived from human embryonic stem cell-induced mesodermal precursor cells have been shown to produce both lineages of mesenchymal stem cells and endothelial cells (30,31), so supporting a hypothesis that both mesenchymal and endothelial lineage organizer cells can develop from the splanchnic mesodermal plate.…”

“…Hydrophobic polyvinylidene difluoride filters of MultiScreen-IP Filter Plate (Millipore) were coated with 15 mg/ml NP 3 -BSA (for high-affinity AFCs) or NP 30 Abs and secondary reagents anti-ER-TR7 and FDC-M2 Abs were purchased from Santa Cruz Biotechnology and ImmunoKontact, respectively. Alexa Fluor 488-or Alexa Fluor 594-conjugated donkey anti-rat secondary reagents were purchased from Molecular Probes.…”

A human ESC model for MLL-AF4 leukemic fusion gene reveals an impaired early hematopoietic-endothelial specification

“…However, whether a potential endothelial dysfunction in MLL-AF4+ pro-B ALL patients exists remains to be clinically assessed. Interestingly, it has recently been demonstrated the existence of a common precursor of MSCs and endothelial cells, the mesenchymoangioblast, using hESCs directed towards mesendodermal differentiation [34]. The existence of such a common embryonic precursor for MSCs and endothelium, and the reported expression of MLL-AF4 in both leukemic blasts and MSCs in the BM of infant patients suggest that MLL-AF4 fusion might arise and display a developmental impact on early pre-hematopoietic mesodermal or hemangioblastic precursors.…”

Icariin-treated human umbilical cord mesenchymal stem cells decrease chronic liver injury in mice

“…MSCs, derived from mesoderm and neural crest, are adult progenitor cells with a multidirectional differentiation potential (Slukvin and Vodyanik 2011;Vodyanik et al 2010;Takashima et al 2007). Studies have demonstrated that MSCs can differentiate into hepatocytes because of their mesenchymal differentiation capabilities (Hong et al 2005;Lee et al 2004;Snykers et al 2009).…”