Stem cells and biomaterials for treatment of CNS diseases

Stem cells have been investigated for their therapeutic potential in spinal cord injury (SCI), stroke and animal models of amyotrophic lateral sclerosis (ALS). We compared human mesenchymal stem cells (MSC) from bone marrow, a conditionally immortalized human stem cell line from fetal spinal cord (SPC-01) and human induced pluripotent stem cell-derived neural precursors (iPS-NPs) for their capacity to migrate towards lesion sites, differentiate and induce better regeneration. Rat models were used; SCI was caused using a balloon-induced compression lesion, stroke was induced using a photochemical cortical lesion, and ALS was observed in transgenic rats. We studied transplantation of MSC, SPC-01 or iPS-NPs labeled in culture with iron-oxide nanoparticles for MRI tracking. Electrophysiology was used to study the properties of stem cell-derived neurons in vitro. Animals were tested using motor and sensory tests. We found improved function in animals with a stroke lesion as well as prolongation of lifespan and decreased motorneuronal loss in animals with ALS. Various biocompatible hydrogels (degradable and non-degradable), including those based on non-woven nanofibres, have been developed for bridging tissue defects and for use as 3D stem cell carriers. Animals with chronic SCI were implanted with a PHPMA hydrogel seeded in vitro with cells. Ca2+ imaging on single SPC-01 cells revealed voltage-activated Ca2+ channels, typically observed in neurons. In vivo MRI proved that MSC, SPC-01 or iPS-NPs migrated into the lesion and survived for several months. Implanted animals showed functional improvement; MSCs rarely differentiated into neurons, while SPC-01 or iNP-NP implantation resulted in greater improvement, and many implanted cells differentiated into motoneurons. Improved motor and sensory scores in chronic SCI was found after the implantation of biomaterials seeded with MSC or SPC-01. Recently, we also used hydrogels composed of decellularized porcine extracellular matrix (ECM), which can facilitate constructive remodelling of various tissues. After implantation into SCI, we found considerable ingrowth of neurofilaments and blood vessels into this biological scaffold. The ECM biological scaffolds are therefore promising candidates for clinical use not only in the oesophagus, lower urinary tract, muscles, tendons and myocardium, but even in spinal cord repair. Two clinical trials are currently running using autologous MSCs in patients with SCI and ALS.