Combination therapy with human amniotic epithelial cells and hyaluronic acid promotes immune balance recovery in type 1 diabetic rats through local engraftment.

Stem cell engraftment is currently a promising approach for type 1 diabetes mellitus (T1DM) treatment. In our previous study, engraftment of a combination of human amniotic epithelial cells (hAECs) and hyaluronic acid (HA) showed potent anti-diabetic effect in streptozotocin (STZ)-induced T1DM mice via tail vein injection. Here, we adopted a different route of stem cell delivery, that is via pancreatic subcapsular transplantation. This combined local engraftment of hAECs and HA in STZ-induced T1DM rats showed potent anti-diabetic activity, leading to stronger hypoglycaemia, more intact islet structure and increased number of insulin-positive cells compared with those with hAECs or insulin treatments. Engraftment of hAECs alone increased the proportion of Th1 and T-reg cells and decreased the proportion of Th2 and Th17 cells to protect islet ß cells in STZ-induced T1DM rats, whereas the combined engraftment of hAECs and HA showed more potent regulatory capacity, considerably decreased the level of TNF-α and IL-17 and increased the level of TGF-ß1 compared with those by other treatments. The potent synergistic effect of HA contributed to the recovery of immune balance in the diabetic rat model, thereby suggesting a new strategy for effective treatment of T1DM.

Effects of hyaluronic acid on differentiation of human amniotic epithelial cells and cell-replacement therapy in type 1 diabetic mice.

Our hypothesis is that hyaluronic acid may regulate the differentiation of human amniotic epithelial cells (hAECs) into insulin-producing cells and help the treatment of type 1 diabetes. Herein, a protocol for the stepwise in vitro differentiation of hAECs into functional insulin-producing cells was developed by mimicking the process of pancreas development. Treatment of hAECs with hyaluronic acid enhanced their differentiation of definitive endoderm and pancreatic progenitors. Endodermal markers Sox17 and Foxa2 and pancreatic progenitor markers Pax6, Nkx6.1, and Ngn3 were upregulated an enhanced gene expression in hAECs, but hAECs did not express the ß cell-specific transcription factor Pdx1. Interestingly, hyaluronic acid promoted the expression of major pancreatic development-related genes and proteins after combining with commonly used inducers of stem cells differentiation into insulin-producing cells. This indicated the potent synergistic effects of the combination on hAECs differentiation in vitro. By establishing a multiple injection transplantation strategy via tail vein injections, hAECs transplantation significantly reduced hyperglycemia symptoms, increased the plasma insulin content, and partially repaired the islet structure in type 1 diabetic mice. In particular, the combination of hAECs with hyaluronic acid exhibited a remarkable therapeutic effect compared to both the insulin group and the hAECs alone group. The hAECs' paracrine action and hyaluronic acid co-regulated the local immune response, improved the inflammatory microenvironment in the damaged pancreas of type 1 diabetic mice, and promoted the trans-differentiation of pancreatic α cells into ß cells. These findings suggest that hyaluronic acid is an efficient co-inducer of the differentiation of hAECs into functional insulin-producing cells, and hAECs treatment with hyaluronic acid may be a promising cell-replacement therapeutic approach for the treatment of type 1 diabetes.

Gender differences in the human mirror system: a magnetoencephalography study.

The present study investigated whether the human mirror-neuron system exhibits gender differences. Neuromagenetic mu (approximately 20 Hz) oscillations were recorded over the right primary motor cortex, which reflect the mirror neuron activity, in 10 female and 10 male participants while they observed the videotaped hand actions and moving dot. In accordance with previous studies, all participants had mu suppression during the observation of hand action, indicating activation of primary motor cortex. Interestingly, the female participants displayed apparently stronger (P < 0.05) suppression for the hand action than for the moving dot whereas the men showed the opposite (P < 0.05). These findings have implications for the extreme male brain theory of autism and support the hypothesis of a dysfunctional mirror-neuron system in autism.

Modulation of spinal excitability during observation of bipedal locomotion.

This study investigated whether a mirror mechanism exists for bipedal locomotion. We employed the soleus (plantar flexor) Hoffman reflex to investigate corticospinal excitability at the spinal level during observation of bipedal locomotion. The differential amplitude modulation of the left soleus Hoffman reflex during observation of bipedal heel-stepping (plantar dorsiflexion) (324+/-53 microV), standing still (383+/-60 microV), and bipedal toe-stepping (plantar flexion) (419+/-53 microV) reached significance (P < 0.05). The observation of bipedal toe-stepping produced a greater increase in spinal excitability than the observation of bipedal heel-stepping. These findings support the suggestion that there is a mirror mechanism for bipedal locomotion and they demonstrate that spinal excitability for observation of bipedal locomotion mirrors that for execution of bipedal locomotion.