Stem Cells Dev. 2019 Nov 8.

Axon degeneration is rescued with human umbilical cord perivascular cells - a potential candidate for neuroprotection after traumatic brain injury.

Barretto TA1,2, Park K3, Maghen L4, Park E5, Kenigsberg S6, Gallagher D7, Liu E8, Gauthier-Fisher A9, Librach C10,11,12,13, Baker A14,15.

Author information
1
14
University of Toronto, 7938, Anesthesia, Toronto, Ontario, Canada.
15
Saint Michael's Hospital, 10071, Critical Care, Toronto, Ontario, Canada; bakera@smh.ca.
Abstract
Traumatic brain injury leads to delayed secondary injury events consisting of cellular and molecular cascades, that exacerbate the initial injury. Human umbilical cord perivascular cells (HUCPVC) secrete neurotrophic and pro-survival factors. Here we examined the effects of HUCPVC in sympathetic axon and cortical axon survival models and sought to determine whether HUCPVC provide axonal survival cues. We then examined the effects of the HUCPVC in an in vivo fluid percussion injury (FPI) model of traumatic brain injury (TBI). Our data indicate that HUCPVC express neurotrophic and neural survival factors. They also express and secrete relevant growth and survival proteins when cultured alone, or in the presence of injured axons. Co-culture experiments indicate that HUCPVC interact preferentially with axons when co-cultured with sympathetic neurons and reduce axonal degeneration. NGF withdrawal in axonal compartments resulted in 66 ? 3 % axon degeneration whereas HUCPVC co-culture rescued axon degeneration, to 35 ? 3 %. Inhibition of Akt (LY294002) resulted a significant increase in degeneration compared to HUCPVC co-cultures (48 ? 7% degeneration). Under normoxic conditions, control cultures showed 39 ? 5% degeneration. OGD resulted in 58 ? 3% degeneration and OGD HUCPVC co-cultures reduced degeneration to 34 ? 5% (p<0.05). In an in vivo model of TBI, immunohistochemical analysis of NF200 showed improved axon morphology in HUCPVC-treated animals compared to injured animals. The data presented here indicate an important role for perivascular cells in protecting axons from injury and a potential cell-based therapy to treat secondary injury after TBI.


https://www.ncbi.nlm.nih.gov/pubmed/31701812