title: Hyaluronic acid-laminin hydrogels increase neural stem cell transplant retention and migratory response to SDF-1α.
abstract: The chemokine SDF-1α plays a critical role in mediating stem cell response to injury and disease and has specifically been shown to mobilize neural progenitor/stem cells (NPSCs) towards sites of neural injury. Current neural transplant paradigms within the brain suffer from low rates of retention and engraftment after injury. Therefore, increasing transplant sensitivity to injury-induced SDF-1α represents a method for increasing neural transplant efficacy. Previously, we have reported on a hyaluronic acid-laminin based hydrogel (HA-Lm gel) that increases NPSC expression of SDF-1α receptor, CXCR4, and subsequently, NPSC chemotactic migration towards a source of SDF-1α in vitro. The study presented here investigates the capacity of the HA-Lm gel to promote NPSC response to exogenous SDF-1α in vivo. We observed the HA-Lm gel to significantly increase NPSC transplant retention and migration in response to SDF-1α in a manner critically dependent on signaling via the SDF-1α-CXCR4 axis. This work lays the foundation for development of a more effective cell therapy for neural injury, but also has broader implications in the fields of tissue engineering and regenerative medicine given the essential roles of SDF-1α across injury and disease states.
authors.affiliation: School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, United States.
authors.forename: C P
authors.initials: CP
authors.lastname: Addington
authors.affiliation: Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, United States.
authors.forename: S
authors.initials: S
authors.lastname: Dharmawaj
authors.affiliation: School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, United States; Barrow Brain Tumor Research Center, Barrow Neurological Institute, Phoenix, AZ, United States.
authors.forename: J M
authors.initials: JM
authors.lastname: Heffernan
authors.affiliation: School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, United States; Barrow Brain Tumor Research Center, Barrow Neurological Institute, Phoenix, AZ, United States.
authors.forename: R W
authors.initials: RW
authors.lastname: Sirianni
authors.affiliation: School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, United States. Electronic address: sarah.stabenfeldt@asu.edu.
authors.forename: S E
authors.initials: SE
authors.lastname: Stabenfeldt
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000139:chemically induced / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D002465:Cell Movement / Q000187:drug effects; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D054377:Chemokine CXCL12 / Q000378:metabolism / Q000494:pharmacology*; D004622:Embryo, Mammalian; D015870:Gene Expression; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D020100:Hydrogels / Q000737:chemistry / Q000494:pharmacology; D007276:Injections, Intraventricular; D007797:Laminin / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D033581:Stem Cell Transplantation; D013238:Stereotaxic Techniques; D054457:Tissue Scaffolds
chemical_list: C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; D020100:Hydrogels; D007797:Laminin; D019718:Receptors, CXCR4; D006820:Hyaluronic Acid
keywords: Biomaterials; CXCL12; Chemotaxis; Neural progenitor cells; Regenerative medicine; Tissue engineering