Manganese-Labeled Alginate Hydrogels for Image-Guided Cell Transplantation.

Antonina M Araszkiewicz,Piotr Walczak,Joaquim Miguel Oliveira,Izabela Malysz-Cymborska,Katarzyna Drela,Michal Fiedorowicz,Eduarda P Oliveira,Terje Svendsen,Piotr Rogujski,Barbara Lukomska,Luiza Stanaszek,Miroslaw Janowski,Rui L Reis

doi:10.3390/ijms23052465

Abstract

Cell transplantation has been studied extensively as a therapeutic strategy for neurological disorders. However, to date, its effectiveness remains unsatisfactory due to low precision and efficacy of cell delivery; poor survival of transplanted cells; and inadequate monitoring of their fate in vivo. Fortunately, different bio-scaffolds have been proposed as cell carriers to improve the accuracy of cell delivery, survival, differentiation, and controlled release of embedded stem cells. The goal of our study was to establish hydrogel scaffolds suitable for stem cell delivery that also allow non-invasive magnetic resonance imaging (MRI). We focused on alginate-based hydrogels due to their natural origin, biocompatibility, resemblance to the extracellular matrix, and easy manipulation of gelation processes. We optimized the properties of alginate-based hydrogels, turning them into suitable carriers for transplanted cells. Human adipose-derived stem cells embedded in these hydrogels survived for at least 14 days in vitro. Alginate-based hydrogels were also modified successfully to allow their injectability via a needle. Finally, supplementing alginate hydrogels with Mn ions or Mn nanoparticles allowed for their visualization in vivo using manganese-enhanced MRI. We demonstrated that modified alginate-based hydrogels can support therapeutic cells as MRI-detectable matrices.

Highlights

Tissue degeneration constitutes a severe burden for societies with increasing longevity.considerable effort is directed towards regenerative medicine, but optimal types of stem cells and microenvironments able to support their function are still being studied
Whether those properties are altered by the presence/absence of compact manganese alginate particles and by the different calcium alginate (CaM) concentrations (0.5% and 1%) was assessed
To assess the effect of CSF on the hydrogels’ mechanical properties, three types of hydrogels were tested in different conditions: freshly prepared; hydrogel incubated with artificial cerebrospinal fluid for 45 min; hydrogel incubated in the presence of aCSF for 12 h

Summary

Introduction

Tissue degeneration constitutes a severe burden for societies with increasing longevity.considerable effort is directed towards regenerative medicine, but optimal types of stem cells and microenvironments able to support their function are still being studied. Mesenchymal stem cells (MSCs) are currently one of the most commonly used cells in regenerative medicine [3] These cells are known for their paracrine, trophic, and immunomodulatory activities. The administration route should be selected to allow the cells to reach the target and support the appropriate niche. An insufficient number of injected cells reach brain parenchyma, while the intraarterial route allows for a sufficient number of delivered cells. The latter method is adequate for injuries related to massive tissue damage caused by stroke or ischemia, where infused cells possess suitable conditions to migrate into the parenchyma. Cell migration from cerebrospinal fluid (CSF) to the spine parenchyma has not been well described [7]

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