Schwann Cell But Not Olfactory Ensheathing Glia Transplants Improve Hindlimb Locomotor Performance in the Moderately Contused Adult Rat Thoracic Spinal Cord

Abstract

Cultured adult rat Schwann cells (SCs) or olfactory ensheathing glia (OEG), or both, were transplanted in the adult Fischer rat thoracic (T9) spinal cord 1 week after a moderate contusion (10 gm, 12.5 mm, NYU impactor). Rats received either a total of 2 x 10(6) cells suspended in culture medium or culture medium only (controls). At 12 weeks after injury, all grafted animals exhibited diminished cavitation. Although in medium-injected rats 33% of spinal tissue within a 5-mm-long segment of cord centered at the injury site was spared, significantly more tissue was spared in SC (51%), OEG (43%), and SC/OEG (44%) grafted animals. All three types of glial grafts were filled with axons, primarily of spinal origin. SC grafts contained more myelinated axons than SC/OEG and OEG grafts. Both types of SC-containing grafts expressed more intense staining for glial fibrillary acidic protein and chondroitin sulfate proteoglycan compared with OEG-only grafts. Retrograde tracing demonstrated that the number of propriospinal and brainstem axons reaching 5-6 mm beyond the grafted area was significantly higher with SC and SC/OEG grafts but not with OEG-only grafts compared with controls. Corticospinal fibers terminated closer to the lesion epicenter in all grafted animals than in controls. With SC-only grafts, a modest but statistically significant improvement in hindlimb locomotor performance was detected at 8-11 weeks after injury. Thus, in addition to this functional improvement, our results show that an SC graft is more effective in promoting axonal sparing/regeneration than an SC/OEG or OEG graft in the moderately contused adult rat thoracic spinal cord.

Setting the stage for functional repair of spinal cord injuries: a cast of thousands

“…When SCs and OECs were injected (separately and together) into acute thoracic contusion injuries in rat, both cells induced tissue sparing and angiogenesis at the lesion; however, functional outcome was only improved in animals that received SCs. 243 SCs were also recently reported to support regeneration of rat retinal ganglion axons, while OECs applied in the same manner did not. 259 In a recent combination study, SCs bridged a thoracic contusion site to support growth and remyelination in rolipram and cAMP-treated animals (see 'Casting the combination', below).…”

“…Recent data suggest that the mechanism of functional return may be more complex than regrowth of lesioned axons. In fact, OEC transplantation protects spinal tissue from secondary damage and prevents cavitation, [241][242][243][244][245][246] enhances vascularization of the lesion site 235,246 and promotes branching of neighboring axons spared by the primary injury, 247 all of which might subserve improved functional outcome. While earlier transplant experiments sought to isolate OECs without other cellular components of the olfactory nerve, recent work suggests that the recovery of function is enhanced by including other cell types, such as olfactory nerve fibroblasts (ONFs), in the graft.…”

“…316,317 When OECs and SCs were grafted at the same type of contusion injury, more myelinated axons were found within SC-containing grafts than within OEC-only grafts. 243 Importantly, peripherally myelinated axons were also found in nontransplanted lesions, demonstrating that host SCs could access the untreated contusion site, in limited numbers, and produce myelin. 243 Remyelination has also been achieved by stimulating Schwann cell immigration via cellular delivery of GDNF at the site of thoracic transection.…”

“…243 Importantly, peripherally myelinated axons were also found in nontransplanted lesions, demonstrating that host SCs could access the untreated contusion site, in limited numbers, and produce myelin. 243 Remyelination has also been achieved by stimulating Schwann cell immigration via cellular delivery of GDNF at the site of thoracic transection. 318 Recently, Boyd et al 261 used virally labeled OECs to demonstrate that peripheral myelin that formed within the OECtransplanted site of SCI was derived entirely from invading host SCs and not from grafted OECs.…”

Updates on stem cells and their applications in regenerative medicine

“…Since present in the skin, SKPs are a widely available and accessible source of neural precursors which can be used for regenerative therapies of the nervous system. To date, studies have been undertaken on the use of Schwann cells for spinal cord injuries (Takami et al, 2002, Pearse et al 2004 Marchesi et al (2007) implanted L-lactide and trimethylene carbonate (PLA-TMC), or collagen guides with SKPs, into 16 mm sciatic nerve gaps in adult mice. The authors claim that SKPs led to significantly higher recovery and neuroregeneration than control guides filled only with phosphate buffer solution.…”