IL-10 lentivirus-laden hydrogel tubes increase spinal progenitor
survival and neuronal differentiation after spinal cord injury
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.