Neural progenitors generated from the mesenchymal stem cells of first-trimester human placenta matured in the hypoxic-ischemic rat brain and mediated restoration of locomotor activity

Term placenta is a great reservoir of mesenchymal stem cells (MSCs), however, the potential of the earlier placenta is largely unknown. In this report, we established 17 MSC lines from 19 first-trimester human placenta (fPMSC). fPMSC proliferated for 90–150 days in vitro and by enhanced cellular interaction, fPMSC differentiated into nestin-expressing neural progenitor cells (fPMSC-NP), accompanied by inductions of immature neuron-specific genes. Therapeutic effect of the fPMSC-NP was tested in the animal model of hypoxia-ischemia (HI) which was devastating to dopaminergic neurons and to locomotor activity. Improvement of motor activity was evident as early as 2 weeks after transplantation of the fPMSC-NP into bilateral striatum and became indistinguishable from that of the age-matched normal animals by 8 weeks but no spontaneous recovery was observed in the control-grafted animals. Immunohistochemical analyses revealed that the implanted fPMSC-NP matured into ectodermal cells including the tyrosine hydroxylase (TH)-expressing neurons in the recipient striatum. So, the improved motor behavior was likely due to the dopaminergic differentiation of the implanted fPMSC-NP in the dopaminergic-denervated host brain. Based on this result, we propose that progenitors may be more advantageous than the terminally differentiated cells for the purpose of cell replacement therapies since the progenitors are easily obtainable and are expected to be more pliable to the new environment.