This study assessed the potential of highly purified (Stro-1(+)) human mesenchymal precursor cells (hMPCs) in combination with the anti-
scarring protein decorin to repair the injured spinal cord (SC). Donor hMPCs isolated from
spinal cord injury (SCI) patients were transplanted into athymic rats as a
suspension graft, alone or after previous treatment with, core (
decorin(core)) and
proteoglycan (
decorin(pro))
isoforms of purified human recombinant
decorin.
Decorin was delivered via mini-osmotic pumps for 14 days following sub-acute (7 day) or chronic (1 month) SCI. hMPCs were delivered to the spinal cord at 3 weeks or 6 weeks after the initial injury at T9 level. Behavioral and anatomical analysis in this study showed statistically significant improvement in functional recovery, tissue sparing and
cyst volume reduction following hMPC
therapy. The combination of
decorin infusion followed by hMPC
therapy did not improve these measured outcomes over the use of
cell therapy alone, in either sub-acute or chronic SCI regimes. However,
decorin infusion did improve tissue sparing, reduce spinal tissue cavitation and increase transplanted cell survivability as compared to controls. Immunohistochemical analysis of spinal cord sections revealed differences in glial, neuronal and extracellular matrix molecule expression within each experimental group. hMPC transplanted spinal cords showed the increased presence of serotonergic (5-HT) and sensory (CGRP) axonal growth within and surrounding transplanted hMPCs for up to 2 months; however, no evidence of hMPC transdifferentiation into neuronal or glial phenotypes. The number of hMPCs was dramatically reduced overall, and no transplanted cells were detected at 8 weeks post-injection using lentiviral GFP labeling and human
nuclear antigen antibody labeling. The presence of recombinant
decorin in the
cell transplantation regimes delayed in part the loss of donor cells, with small numbers remaining at 2 months after
transplantation. In vitro co-culture experiments with embryonic dorsal root ganglion explants revealed the growth promoting properties of hMPCs.
Decorin did not increase axonal outgrowth from that achieved by hMPCs. We provide evidence for the first time that (Stro-1(+)) hMPCs provide: i) an advantageous source of allografts for
stem cell transplantation for sub-acute and chronic spinal cord
therapy, and (ii) a positive host microenvironment that promotes tissue sparing/repair that subsequently improves behavioral outcomes after SCI. This was not measurably improved by recombinant
decorin treatment, but does provide important information for the future development and potential use of
decorin in contusive SCI
therapy.