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Proteolytic Rafts for Improving Intraparenchymal Migration of Minimally Invasively Administered Hydrogel-Embedded Stem Cells
The physiological spaces (lateral ventricles, intrathecal space) or pathological cavities (stroke lesion, syringomyelia) may serve as an attractive gateway for minimally invasive deployment of stem cells. Embedding stem cells in injectable scaffolds is essential when transplanting into the body cavi...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628268/ https://www.ncbi.nlm.nih.gov/pubmed/31238564 http://dx.doi.org/10.3390/ijms20123083 |
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author | Piejko, Marcin Jablonska, Anna Walczak, Piotr Janowski, Miroslaw |
author_facet | Piejko, Marcin Jablonska, Anna Walczak, Piotr Janowski, Miroslaw |
author_sort | Piejko, Marcin |
collection | PubMed |
description | The physiological spaces (lateral ventricles, intrathecal space) or pathological cavities (stroke lesion, syringomyelia) may serve as an attractive gateway for minimally invasive deployment of stem cells. Embedding stem cells in injectable scaffolds is essential when transplanting into the body cavities as they secure favorable microenvironment and keep cells localized, thereby preventing sedimentation. However, the limited migration of transplanted cells from scaffold to the host tissue is still a major obstacle, which prevents this approach from wider implementation for the rapidly growing field of regenerative medicine. Hyaluronan, a naturally occurring polymer, is frequently used as a basis of injectable scaffolds. We hypothesized that supplementation of hyaluronan with activated proteolytic enzymes could be a viable approach for dissolving the connective tissue barrier on the interface between the scaffold and the host, such as pia mater or scar tissue, thus demarcating lesion cavity. In a proof-of-concept study, we have found that collagenase and trypsin immobilized in hyaluronan-based hydrogel retain 60% and 28% of their proteolytic activity compared to their non-immobilized forms, respectively. We have also shown that immobilized enzymes do not have a negative effect on the viability of stem cells (glial progenitors and mesenchymal stem cells) in vitro. In conclusion, proteolytic rafts composed of hyaluronan-based hydrogels and immobilized enzymes may be an attractive strategy to facilitate migration of stem cells from injectable scaffolds into the parenchyma of surrounding tissue. |
format | Online Article Text |
id | pubmed-6628268 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-66282682019-07-23 Proteolytic Rafts for Improving Intraparenchymal Migration of Minimally Invasively Administered Hydrogel-Embedded Stem Cells Piejko, Marcin Jablonska, Anna Walczak, Piotr Janowski, Miroslaw Int J Mol Sci Article The physiological spaces (lateral ventricles, intrathecal space) or pathological cavities (stroke lesion, syringomyelia) may serve as an attractive gateway for minimally invasive deployment of stem cells. Embedding stem cells in injectable scaffolds is essential when transplanting into the body cavities as they secure favorable microenvironment and keep cells localized, thereby preventing sedimentation. However, the limited migration of transplanted cells from scaffold to the host tissue is still a major obstacle, which prevents this approach from wider implementation for the rapidly growing field of regenerative medicine. Hyaluronan, a naturally occurring polymer, is frequently used as a basis of injectable scaffolds. We hypothesized that supplementation of hyaluronan with activated proteolytic enzymes could be a viable approach for dissolving the connective tissue barrier on the interface between the scaffold and the host, such as pia mater or scar tissue, thus demarcating lesion cavity. In a proof-of-concept study, we have found that collagenase and trypsin immobilized in hyaluronan-based hydrogel retain 60% and 28% of their proteolytic activity compared to their non-immobilized forms, respectively. We have also shown that immobilized enzymes do not have a negative effect on the viability of stem cells (glial progenitors and mesenchymal stem cells) in vitro. In conclusion, proteolytic rafts composed of hyaluronan-based hydrogels and immobilized enzymes may be an attractive strategy to facilitate migration of stem cells from injectable scaffolds into the parenchyma of surrounding tissue. MDPI 2019-06-24 /pmc/articles/PMC6628268/ /pubmed/31238564 http://dx.doi.org/10.3390/ijms20123083 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Piejko, Marcin Jablonska, Anna Walczak, Piotr Janowski, Miroslaw Proteolytic Rafts for Improving Intraparenchymal Migration of Minimally Invasively Administered Hydrogel-Embedded Stem Cells |
title | Proteolytic Rafts for Improving Intraparenchymal Migration of Minimally Invasively Administered Hydrogel-Embedded Stem Cells |
title_full | Proteolytic Rafts for Improving Intraparenchymal Migration of Minimally Invasively Administered Hydrogel-Embedded Stem Cells |
title_fullStr | Proteolytic Rafts for Improving Intraparenchymal Migration of Minimally Invasively Administered Hydrogel-Embedded Stem Cells |
title_full_unstemmed | Proteolytic Rafts for Improving Intraparenchymal Migration of Minimally Invasively Administered Hydrogel-Embedded Stem Cells |
title_short | Proteolytic Rafts for Improving Intraparenchymal Migration of Minimally Invasively Administered Hydrogel-Embedded Stem Cells |
title_sort | proteolytic rafts for improving intraparenchymal migration of minimally invasively administered hydrogel-embedded stem cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628268/ https://www.ncbi.nlm.nih.gov/pubmed/31238564 http://dx.doi.org/10.3390/ijms20123083 |
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