Regenerative potential of primary adult human neural stem cells on micropatterned bio-implants boosts motor recovery

Abstract

BackgroundThe adult brain is unable to regenerate itself sufficiently after large injuries. Therefore, hopes rely on therapies using neural stem cell or biomaterial transplantation to sustain brain reconstruction. The aim of the present study was to evaluate the improvement in sensorimotor recovery brought about by human primary adult neural stem cells (hNSCs) in combination with bio-implants.MethodshNSCs were pre-seeded on implants micropatterned for neurite guidance and inserted intracerebrally 2 weeks after a primary motor cortex lesion in rats. Long-term behaviour was significantly improved after hNSC implants versus cell engraftment in the grip strength test. MRI and immunohistological studies were conducted to elucidate the underlying mechanisms of neuro-implant integration.ResultshNSC implants promoted tissue reconstruction and limited hemispheric atrophy and glial scar expansion. After 3 months, grafted hNSCs were detected on implants and expressed mature neuronal markers (NeuN, MAP2, SMI312). They also migrated over a short distance to the reconstructed tissues and to the peri-lesional tissues, where 26% integrated as mature neurons. Newly formed host neural progenitors (nestin, DCX) colonized the implants, notably in the presence of hNSCs, and participated in tissue reconstruction. The microstructured bio-implants sustained the guided maturation of both grafted hNSCs and endogenous progenitors.ConclusionsThese immunohistological results are coherent with and could explain the late improvement observed in sensorimotor recovery. These findings provide novel insights into the regenerative potential of primary adult hNSCs combined with microstructured implants.

Focal Malonate Injection Into the Internal Capsule of Rats as a Model of Lacunar Stroke

“…To evaluate maximal forelimb muscle grip strength, the animals grasped a horizontal bar of the Grip Strength Meter (Bioseb, France) attached to a dynamometer, and then they were gently pulled away by an experienced handler until their grasp was broken. This test was validated in previous studies by the group (19, 21, 23). The dynamometer measured the maximal isometric force before the animal released the bar.…”

“…The lesioned hemisphere was the dominant one. The stereotaxic coordinates targeted, were: AP −1.5 mm, ML +3.2 mm, DV −5.3 mm (20), as previously determined from primary motor cortically injured rat brain slices with evidence of corticospinal tract degeneration (21). After the injection, the needle was left in place for additional 4 min to avoid backflow.…”

Wet spinning and radial self-assembly of a carbohydrate low molecular weight gelator into well organized hydrogel filaments

“…25 Still in the context of neuronal cell culture, it has been shown that oriented scaffolds are able to guide the development of neurites and axons in one preferential direction and can help in a suitable tissue reconstruction. [26][27][28] Thus, for the scaffolding purpose, and also more generally for extending the scope of LMWG applications, our objective was to explore how fluidics (or microfluidics) can drive the self-assembly of the gelator into well-defined structures and shapes.…”

Harnessing the Potential of Biomaterials for Brain Repair after Stroke

“…The authors reported significant motor recovery and increased cell survival 3 weeks after implantation compared to the sham animals (Vaysse et al, 2015). In a follow-up publication, the host response to the scaffold was analyzed: there was no significant increase in activated ED1-positive microglia at the implant site and surprisingly a decrease in the astrogliosis response compared to the sham (Davoust et al, 2017), suggesting that the implant is well tolerated long-term. Future studies could also focus on combining topographical cues with some of the factors discussed in previous sections known to promote connectivity and plasticity in the brain (Wei et al, 2007;Bliss et al, 2010).…”