title: Strategies for endogenous spinal cord repair: HPMA hydrogel to recruit migrating endogenous stem cells.
abstract: Injury to the spinal cord disrupts ascending and descending axonal pathways and causes tissue damage with a subsequent limited cellular regeneration. Successful treatment would encompass the restoration of the cytoarchitecture, homeostasis and function all in dear need. Transplantation-based treatments using exogenous cells are the most favoured approach. Yet, with the advent of the stem cell concept and continuous progress in the field it became clear that the endogenous potential for repair is greater than previously thought. As an alternative to neural grafting, we and other researchers have aimed at understanding what are the elements needed for a successful repair with self progenitors that would give rise to the cell types needed to restore function of the central nervous system. Some studies involve both scaffolds and cell grafts. Here we describe studies on spinal cord repair using what we call "endogenous tissue engineering for regenerative medicine". The approach involves a hydrogel that mimics the natural milieu where endogenous pre-existing and newly formed cells populate the gel progressively allowing for the integration of CNS self populations leading to a successful recovery of function. Highlight aspects learned from this type of studies are that: Endogenous reconstruction of the injured spinal cord is possible by using the adequate support. The contribution of nestin-expressing progenitors to spinal cord regeneration is continuous and substantial both, in the reconstructed segment as well as, along the distal and caudal segments of the reconstructed spinal cord. Most of these cells appear to have been in a quiescent state until the injury occurred and only a small fraction of these neural progenitors was produced via cell proliferation. The hydrogel combined with exercise was necessary and sufficient to restore locomotor function in cats that underwent spinal transaction followed by reconstructive surgery. This recovery of function was first seen 28 days after surgery and continued to improve for at least 21 months. Therefore, endogenous pre-existing and newly formed cells populated the gel scaffold established contact with the non injured tissue and lead to recovery of function.
authors.affiliation: Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience, University of California Los Angeles, Los Angeles, California, USA. aespinosa@mednet.ucla.edu
authors.forename: Araceli
authors.initials: A
authors.lastname: Espinosa-Jeffrey
authors.forename: Karlos
authors.initials: K
authors.lastname: Oregel
authors.forename: Laurent
authors.initials: L
authors.lastname: Wiggins
authors.forename: Remelyn
authors.initials: R
authors.lastname: Valera
authors.forename: Kathrin
authors.initials: K
authors.lastname: Bosnoyan
authors.forename: Chioma
authors.initials: C
authors.lastname: Agbo
authors.forename: Oluwole
authors.initials: O
authors.lastname: Awosika
authors.forename: Paul M
authors.initials: PM
authors.lastname: Zhao
authors.forename: Jean
authors.initials: J
authors.lastname: de Vellis
authors.forename: Stéphane
authors.initials: S
authors.lastname: Woerly
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D002415:Cats; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000627:therapeutic use; D008689:Methacrylates / Q000627:therapeutic use*; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology*; D051381:Rats; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000628:therapy*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D015415:Biomarkers; D008689:Methacrylates; D009419:Nerve Tissue Proteins; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C032802:hydroxypropyl methacrylate