Isolation of progenitors with regenerative potential and their in vitro induction to specific lineage may be necessary for effective cell transplantation outcome. Earlier, we standardized specific niche for derivation of neural progenitor cells (NPCs) from circulating mononuclear cells to neural like cells (NLC) in vitro, for applications in neural regeneration. The current study analysed the prospective involvement of signaling mechanism for in vitro lineage commitment of circulating NPCs. Preferred mechanism selected was Wnt-like signaling because this is one of the pathways implicated in the central nervous system (CNS) development and homeostasis. We sought to determine the activation of Wnt3a-specific genes in the standardized NPC culture system. To start with, it was found that when standardized NPC culture niche was supplemented with Wnt 3a protein, no additional morphological changes happen. Chemical inhibitors of the pathway retarded NPC to NLC conversion both in the absence and presence of supplemented Wnt-3a. In earlier studies, involvement of the niche constituents- fibronectin (FN), laminin (La) and fibrin (Fib)- for NPC growth and differentiation was established. In an attempt to study the role of these adhesive proteins by adding antibodies against FN, La & Fib together, molecular level signaling changes seen were comparable to that occur in response to Wnt3a chemical inhibitor. Therefore, induction of Wnt 3a-like signal from the matrix-dependent niche constituents may be implicated in the differentiation of NPC to NLC. The results substantiate the potential applications of the fibrin-based composite niche in neural engineering for regeneration.
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The authors acknowledge The Head, Biomedical Technology Wing and The Director of SCTIMST for the encouragement and support throughout this study. We thank Ms. Priyanka S and Mr. Ranjith S of the Thrombosis Research Unit for providing human fibrinogen and thrombin. This work was supported by the project grant received by Department of Science and Technology (DST), Govt of India to LKK; Council of Scientific and Industrial Research and Indian Council of Medical Research fellowships, Govt of India, to Tara S.
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