Biology Reference
In-Depth Information
rat spinal cord 10 months after injury failed to promote remyelination and
functional recovery (
Keirstead et al., 2005
). Of note, tissue sparing remained
unchanged in treated and control animals. In a follow-up study, identical
hESC-derived OPC grafted 7 days after a rat cervical midline contusion
injury promoted gray and white matter sparing (neuroprotection) paralleled
by recovery of locomotor function compared to the nontransplanted group
(
Sharp et al., 2010
). Surprisingly, in this study, remyelination was not in-
creased after OPC grafting.
In early 2009, the U.S. Food and Drug Administration approved the first
clinical trial with hESC-derived OPC for transplantation after acute SCI.
Geron Corp. initiated a phase I multicenter trial in patients with complete
thoracic SCI (AIS grade A). Two million hESC-derived OPCwere injected
into the spinal cord lesion site within 14 days after injury accompanied by
immunosuppression with tacrolimus. The trial's primary end point was
safety (adverse events related to the injected stem cells, the injection proce-
dure, or the immunosuppressive treatment). Neurological function was
assessed as a secondary end point (
Mayor, 2010
). In November 2011, the
company announced to discontinue the clinical trial for financial reasons af-
ter five patients underwent the cell transplantation procedure. Apparently
establishing proper cell purification protocols, problems with cyst
formation after transplantation and slow patient recruitment caused an
unforeseeable cost explosion. It took around 12 years from the bench
all the way to the clinical trial. Developmental costs for this stem
cell-based therapy to the point of first patient enrollment in 2010
were estimated $170 million
(
http://content.usatoday.com/com-
of-embryonic-stem-cell-on-humans/1#.T8U_OJgjPCY
)
. According to
the company, the therapy did not promote any improvement but was
well tolerated with no serious adverse events (
Kaiser, 2011
).
The prime goal of OPC grafting to replace oligodendroglia and thus pro-
mote remyelination and functional recovery is based on the evidence that
even in the most severe cases of SCI (AIS grade A) a spared rim of
demyelinated axons remains (
Kakulas, 1999
). However, it has yet to be
demonstrated that spared axon remyelination alone is sufficient to
promote relevant functional recovery. Conflicting preclinical data exist
for remyelinating capacities of hESC-derived OPC in different lesion
models (
Keirstead et al., 2005; Sharp et al., 2010
). The approach was
not recapitulated by an independent laboratory before translation into a
clinical trial.
