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IL-10 lentivirus-laden hydrogel tubes increase spinal progenitor survival and neuronal differentiation after spinal cord injury
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  • Andrew Ciciriello,
  • Dominique Smith,
  • Mary Munsell,
  • Sydney Boyd,
  • Lonnie Shea,
  • Courtney Dumont
Andrew Ciciriello
University of Miami
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Dominique Smith
University of Michigan
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Mary Munsell
University of Michigan
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Sydney Boyd
University of Miami
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Lonnie Shea
University of Michigan
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Courtney Dumont
University of Miami
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Abstract

The pathophysiological response following spinal cord injury (SCI) is characterized by a complex cellular cascade that limits regeneration. Biomaterial and stem cell combination therapies have shown synergistic effects, compared to their interventions independent of each other, and represent a promising approach towards regaining function after injury. In this study, we combine our polyethylene glycol (PEG) cell delivery platform with lentiviral-mediated overexpression of the anti-inflammatory cytokine interleukin (IL)-10 to improve embryonic day 14 (E14) spinal progenitor transplant survival. PEG tubes loaded with lentivirus encoding for IL-10 were implanted immediately following injury into a mouse SCI hemisection model. Two weeks after tube implantation, mouse E14 spinal progenitors were injected directly into the integrated tubes, which served as a soft substrate for cell transplantation. Together, the tubes with the IL-10 encoding lentivirus improved E14 spinal progenitor survival, assessed at two weeks post-transplantation (four weeks post-injury). Mice receiving IL-10 lentivirus-laden tubes had on average 8.1% of E14 spinal progenitors survive compared to 0.7% in mice receiving transplants without tubes, an 11.5-fold difference. Surviving E14 spinal progenitors gave rise to neurons when injected into tubes. Additionally, axon elongation and remyelination was observed, in addition to a faster rate of functional recovery in mice receiving anti-inflammatory tubes with E14 spinal progenitor delivery. This system affords increased control over the transplantation microenvironment, offering the potential to improve stem cell-mediated tissue regeneration.

Peer review status:ACCEPTED

12 Feb 2021Submitted to Biotechnology and Bioengineering
13 Feb 2021Submission Checks Completed
13 Feb 2021Assigned to Editor
13 Feb 2021Reviewer(s) Assigned
01 Mar 2021Review(s) Completed, Editorial Evaluation Pending
01 Mar 2021Editorial Decision: Revise Minor
05 Apr 20211st Revision Received
06 Apr 2021Submission Checks Completed
06 Apr 2021Assigned to Editor
06 Apr 2021Reviewer(s) Assigned
06 Apr 2021Review(s) Completed, Editorial Evaluation Pending
06 Apr 2021Editorial Decision: Accept