Cell based therapy in MS
Friday, October 21, 2011, 14:40 - 14:55
Cell fate of human embryonic stem cell-derived oligodendrocyte progenitors (GRNOPC1) transplanted into the demyelinated nonhuman primate spinal cord
J.D. Kocsis, M. Sasaki, K.L. Lankford, C. Priest, E.D. Wirth, III (West Haven, Menlo Park, US)
In rodent models of chemically-induced demyelination of the spinal cord endogenous myelin repair begins within days and becomes extensive within a few weeks. However, several studies indicate that human oligodendrocyte progenitors (OPCs) require a longer time to remyelinate than rodent OPCs. To study the remyelination potential of human embryonic stem cells induced to differentiate into high purity OPCs (GRNOPC1), we transplanted GRNOPC1 cells into the demyelinated nonhuman primate (NHP) spinal cord. A focal demyelinating lesion was produced in the dorsal columns of the African Green monkey at the T7 level of the spinal cord by microinjection of ethidium bromide (0.3% in normal saline; 1 µl/injection site) at 3 depths spanning the dorsal columns and at 3 longitudinal positions separated by 2 mm. Endogenous repair in this model system does not begin until several months after lesion induction, and at 12 and 16 months the pattern of endogenous remyelination was patchy with islands of remyelinated axons separated by islands of demyelinated axons with a variable number of intervening phagocytic cells. GRNOPC1 cells (3 x 104 cells/µl; 1 µl/injection site) were transplanted 1 week after lesion induction. The animals were prepared for histology at various post-transplant times and semi-thin and thin plastic sections were prepared for light and ultrastructural analysis, respectively. At early post-transplant times (5-8 weeks), the GRNOPC1 injection sites contained numerous cells that survived and integrated into the demyelinated spinal cords. The cells associated with the demyelinated axons by extending cytoplasmic extensions around groups of axons. The transplanted cells had extensive rough endoplasmic reticulum with relatively large nuclei with dense chromatin. At the seven-week time point variable remyelination was observed and macrophages were still present. At 16 weeks after transplantation, remyelination in the GRNOPC1 injection sites was extensive with relatively thick myelin. Some myelin profiles were of a peripheral pattern with a large cytoplasmic and nuclear region and a basement membrane surrounding the myelin. Macrophages were nearly completely cleared at this time point. There was no evidence of ectopic cell differentiation, tissue distortions, tumor formation or other pathological events. Thus, transplantation of GRNOPC1 cells into a persistent demyelinating lesion in the NHP spinal cord resulted in cell survival and with appropriate survival time remyelination of the spinal cord.
Well...yes. For something closer to market, and of interest to the price of this puppy turning into a dog,
search 9%-21% oscillating oxygen supply with spinal injury..... Some variety of such terms will get you to an
The road kill koolade drinkers here will glaze over "demyelinating lesion" .... I didn't.
Biotime has a monopoly on hESC progenitor cell lines, which are now being acknowledged as the 'Gold Standard' of cellular biology. While everyone was jumping on the IPS bandwagon Biotime was advancing their hESC IP. The ownership of hESC master banks as well as isolation, purification, and ACTcelleration makes this technology near impossible to duplicate. Biotimes extra-cellular hydrogels is also top of the line and a rare breed of therapeutic product. Hard to touch this one!