Two in One: Use of Divalent Manganese Ions as Both Cross-Linking and MRI Contrast Agent for Intrathecal Injection of Hydrogel-Embedded Stem Cells

Autor: Lukasz Kalkowski, Dominika Golubczyk, Joanna Kwiatkowska, Piotr Holak, Kamila Milewska, Miroslaw Janowski, Joaquim Miguel Oliveira, Piotr Walczak, Izabela Malysz-Cymborska
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Pharmaceutics, Vol 13, Iss 7, p 1076 (2021)
Druh dokumentu: article
ISSN: 13071076
1999-4923
DOI: 10.3390/pharmaceutics13071076
Popis: 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.
Databáze: Directory of Open Access Journals