Many neurological disorders are caused by a functional loss of neurons and stem-cell-based therapies bring a hope to cure these diseases. Human bone marrow-derived mesenchymal stem cells (hMSCs) are mesodermal stem cells. MSCs preserve the tissue-specific abilities of osteogenic, chondrogenic and adipogenic differentiation. Previous studies reported neurotrophins (NTs) and retinoic acid (RA) stimulate a neuronal transdifferentiation of hMSCs to progenitor-like cells, but not to mature neurons. Uncovering the factors of differentiation into mature neurons from hMSCs was important in neuronal regeneration. Searching the latest references, we found 3 factors may participate in neurogenic hMSCs. (1) Wnt is a crucial cue during embryonic development and adult tissue homeostasis. In central nerve system, canonical Wnt7a signaling cascade regulates neurogenesis such as neurite growth and synaptogenesis, in neural stem or progenitor cells. (2) Studies have reported that the tenascin family members, tenascinC (TnC) and tenascinR (TnR), regulate differentiation and migration, as well as neurite outgrowth and survival in numerous types of neurons. (3) Beside the effects of Wnt7a and tenascin, the dimensions and elasticity of extracellular matrix are also pivotal in stem cell differentiation. In this study, we hypothesize that Wnt7a and tenascin regulate the terminal differentiation in neuronal progenitor-like cells derived from hMSCs. We will analyze the neurogenic effects of hWnt7a and tenascin in NTs/RA –induced progenitor-like cells from hMSCs that culture in type I collagen-based 3D scaffold. The expected results might provide insights on the involvement of Wnt and tenasin-integrin signaling pathway in mature neurogenesis of hMSCs. The yielded information of Wnt7a enhanced neuronal differentiation of hMSCs might aid the therapy of neuronal degenerative diseases.
|Effective start/end date||8/1/14 → 7/31/15|