Adipose-derived stem cells (ASCs) show promise for regenerative medicine researches and able to differentiate into either endothelial or neuronal lineages. The current study aimed to investigate the therapeutic potential of human adipose-derived stem cell for hypoxic-ischemic (HI) brain injury. The HI brain injury was created by right common carotid artery ligation and then exposure to hypoxia (8% O2) for 2h. The human ASCs were differentiated into NPCs and EPCs by culturing ASCs in the chitosan and shear stress microenvironments. The rat pups were divided into 5 groups to receive different treatments by using intra-peritoneum injection, including Naïve, PBS, hASCs, EPCs, NPCs, and combination of EPCs and NPCs (E+N). All rat pups were sacrificed at 7th day after HI. The infracted area and ratio of cell apoptosis were determined by TTC, and Nissl staining. Our results showed significant reduction of cerebral infarction, increase of neurons, and decrease of cell apoptosis after injected with therapeutic cells. Therapeutic effects were analyzed with immunofluorescence staining to detect neurons, astrocytes, and endothelial cells. The quantified results showed that GFAP positive cells on the ischemic side of cortex were lower in therapeutic cell treatment as compared with PBS group. The branch point of vessel and NeuN positive were enhanced after cell therapies for 7 days in HI brain injury. The positive cells with human chromatin staining confirmed the engraftment of transplanted cells homing to the damaged brain. Combination between EPC and NPC involve signaling in Nrp1 signal in EPCs to promote the angiogenesis. Therefore, the progenitor cells from hASCs may benefit as a treatment of HI brain injury.

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