Abstract
Cell therapy is a promising tool for treating central nervous system (CNS) disorders; though, the translational efforts are plagued by ineffective delivery methods. Due to the large contact surface with CNS and relatively easy access, the intrathecal route of administration is attractive in extensive or global diseases such as stroke or amyotrophic lateral sclerosis (ALS). However, the precision and efficacy of this approach are still a challenge. Hydrogels were introduced to minimize cell sedimentation and improve cell viability. At the same time, contrast agents were integrated to allow image-guided injection. Here, we report using manganese ions (Mn2+) as a dual agent for cross-linking alginate-based hydrogels and magnetic resonance imaging (MRI). We performed in vitro studies to test the Mn2+ alginate hydrogel formulations for biocompatibility, injectability, MRI signal retention time, and effect on cell viability. The selected formulation was injected intrathecally into pigs under MRI control. The biocompatibility test showed a lack of immune response, and cells suspended in the hydrogel showed greater viability than monolayer culture. Moreover, Mn2+-labeled hydrogel produced a strong T1 MRI signal, which enabled MRI-guided procedure. We confirmed the utility of Mn2+ alginate hydrogel as a carrier for cells in large animals and a contrast agent at the same time.
Highlights
Based on the T1 weighted magnetic resonance imaging (MRI) scans, we evaluated the signal intensity of the hydrogels, depending on the solvent used for their preparation
Hydrogels dissolved in mannitol produced a more stable signal, with less manganese-specific signal loss over time compared to hydrogels dissolved in NaCl (Figure 1)
Our study showed that it is possible to introduce manganese (II) ions into sodium alginate solution to obtain biomaterial with MRI contrast properties
Summary
Despite the continuous effort and growing number of newly developed drugs, diseases of the central nervous system (CNS) are refractory to treatment, and many diseases are still incurable. Amyotrophic lateral sclerosis (ALS) is an excellent example of a deadly, fatal disease that affects the brain and spinal cord, leading to degeneration and death of upper and lower motor neurons. Replacement of lost motor neurons via transplantation is difficult, if not impossible, so more realistic therapeutic approaches are based on providing trophic support for neurons. One example of that strategy is the transplantation of glial progenitor cells [1,2].
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