Two in One: Use of Divalent Manganese Ions as Both Cross-Linking and MRI Contrast Agent for Intrathecal Injection of Hydrogel-Embedded Stem Cells
Lukasz Kalkowski,
Dominika Golubczyk,
Joanna Kwiatkowska,
Piotr Holak,
Kamila Milewska,
Miroslaw Janowski,
Joaquim Miguel Oliveira,
Piotr Walczak,
Izabela Malysz-Cymborska
Affiliations
Lukasz Kalkowski
Department of Neurosurgery, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland
Dominika Golubczyk
Department of Neurosurgery, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland
Joanna Kwiatkowska
Department of Neurosurgery, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland
Piotr Holak
Department of Surgery and Radiology, Faculty of Veterinary Medicine, University of Warmia and Mazury, 10-719 Olsztyn, Poland
Kamila Milewska
Department of Neurosurgery, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland
Miroslaw Janowski
Center for Advanced Imaging Research, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Joaquim Miguel Oliveira
a3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Guimarães, Portugal
Piotr Walczak
Center for Advanced Imaging Research, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Izabela Malysz-Cymborska
Department of Neurosurgery, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland
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.
