Spinal progenitor cell differentiation in collagen-based hydrogels: Directing oligodendrocyte differentiation using ECM signals

Over 11,000 people sustain spinal cord injury (SCI) each year in the United States [1]. Researchers have examined spinal progenitor cell implantation into the injury area to encourage axonal regeneration and found functional improvement with this treatment [2]. However, transplanted cell viability was low and there was no scaffold for axonal growth within the injured area. By providing a scaffold, cell viability should increase and axonal growth through the injury area should be supported. Further, the implanted spinal progenitor cells differentiated into astrocytes, neurons, and oligodendrocytes. Oligodendrocyte progenitors are promising in promoting functional recovery [3]. Oligodendrocytes mature during neonatal development; therefore, cells are expected to respond favorably to mechanical properties similar to the neonatal environment. The mechanical and extracellular matrix properties of the scaffolds described here have been tuned to direct spinal progenitor cell differentiation toward oligodendrocytes. Thermally gelling systems were developed in 4 combinations: collagen alone, collagen and laminin, collagen and high molecular weight hyaluronic acid (hHA), and collagen, hHA, and laminin. All of these gel types have the same concentration of collagen (1.5 mg/mL), and compressive moduli below 2 kPa, which is within range of neural tissue (between 0.5-8 kPa) [4]. Multi-component hydrogels mimic mechanical properties of neonatal neural tissue most closely. After 5 days in culture, hydrogels provided an environment that allowed for spinal progenitor differentiation into astrocytes, neurons, and oligodendrocytes. Collagen-based hydrogels are viable thermally gelling systems to direct progenitor differentiation. These gels may promote regeneration after SCI in vivo by directing cell differentiation toward oligodendrocytes.