Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Piejko, Marcin, Jablonska, Anna, Walczak, Piotr, Janowski, Miroslaw
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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
_version_ 1783434921340043264
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
work_keys_str_mv AT piejkomarcin proteolyticraftsforimprovingintraparenchymalmigrationofminimallyinvasivelyadministeredhydrogelembeddedstemcells
AT jablonskaanna proteolyticraftsforimprovingintraparenchymalmigrationofminimallyinvasivelyadministeredhydrogelembeddedstemcells
AT walczakpiotr proteolyticraftsforimprovingintraparenchymalmigrationofminimallyinvasivelyadministeredhydrogelembeddedstemcells
AT janowskimiroslaw proteolyticraftsforimprovingintraparenchymalmigrationofminimallyinvasivelyadministeredhydrogelembeddedstemcells