In contrast to hematopoietic stem cells, there is still a lack of definitive cell markers for specific isolation and identification of mesenchymal stem cells (MSCs). Thus a homogenous population of MSCs is only obtained after several passages, when multilineage potential or other distinctive features of very early progenitors may be already somewhat compromised. Recently a novel surface marker the neural ganglioside GD2 has been reported to distinguish MSCs from all other cells within marrow. Here, we found that MSCs derived from umbilical cord (UC-MSCs) also expressed this marker at early-passages. More importantly, UC-MSCs were the only cells within umbilical cord expressing this marker. Compared to unsorted cells, GD2(+)-sorted cells not only possessed much higher clonogenicity and proliferation capacity but also had significantly stronger multi-differentiation potentials. Flow cytometric analysis revealed that GD2(+)-sorted cells showed increased expression of SSEA-4, Oct-4, Sox-2 and Nanog, the typical markers expressed in embryonic stem cells, in comparison to unsorted or GD2-negative MSCs. Take together, our data demonstrate that the cells selected by GD2 are a subpopulation of MSCs with feature of primitive precursor cells and provide evidence that GD2 can be a cell surface marker suitable for the isolation and purification of UC-MSCs in early-passage culture. Copyright 2009 S. Karger AG, Basel.