Abstract
Stem cell therapy with human mesenchymal stem cells (hMSCs) represents a promising strategy in spinal cord injury (SCI). However, both systemic and parenchymal hMSCs administrations show significant drawbacks as a limited number and viability of stem cells in situ. Biomaterials able to encapsulate and sustain hMSCs represent a viable approach to overcome these limitations potentially improving the stem cell therapy. In this study, we evaluate a new agarose/carbomer based hydrogel which combines different strategies to optimize hMSCs viability, density and delivery of paracrine factors. Specifically, we evaluate a new loading procedure on a lyophilized scaffold (soaked up effect) that reduces mechanical stress in encapsulating hMSCs into the hydrogel. In addition, we combine arginine-glycine-aspartic acid (RGD) tripeptide and 3D extracellular matrix deposition to increase the capacity to attach and maintain healthy hMSCs within the hydrogel over time. Furthermore, the fluidic diffusion from the hydrogel toward the injury site is improved by using a cling film that oriented efficaciously the delivery of paracrine factors in vivo. Finally, we demonstrate that an improved combination as here proposed of hMSCs and biomimetic hydrogel is able to immunomodulate significantly the pro-inflammatory environment in a SCI mouse model, increasing M2 macrophagic population and promoting a pro-regenerative environment in situ.
| Original language | English |
|---|---|
| Pages (from-to) | 135-147 |
| Number of pages | 13 |
| Journal | Biomaterials |
| Volume | 75 |
| DOIs | |
| Publication status | Published - Jan 1 2016 |
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Keywords
- Extracellular matrix
- Human mesenchymal stem cells
- Hydrogels
- Inflammation
- Macrophages
- Spinal cord injury
ASJC Scopus subject areas
- Biomaterials
- Bioengineering
- Ceramics and Composites
- Mechanics of Materials
- Biophysics
Cite this
A new three dimensional biomimetic hydrogel to deliver factors secreted by human mesenchymal stem cells in spinal cord injury. / Caron, Ilaria; Rossi, Filippo; Papa, Simonetta; Aloe, Rossella; Sculco, Marika; Mauri, Emanuele; Sacchetti, Alessandro; Erba, Eugenio; Panini, Nicolò; Parazzi, Valentina; Barilani, Mario; Forloni, Gianluigi; Perale, Giuseppe; Lazzari, Lorenza; Veglianese, Pietro.
In: Biomaterials, Vol. 75, 01.01.2016, p. 135-147.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A new three dimensional biomimetic hydrogel to deliver factors secreted by human mesenchymal stem cells in spinal cord injury
AU - Caron, Ilaria
AU - Rossi, Filippo
AU - Papa, Simonetta
AU - Aloe, Rossella
AU - Sculco, Marika
AU - Mauri, Emanuele
AU - Sacchetti, Alessandro
AU - Erba, Eugenio
AU - Panini, Nicolò
AU - Parazzi, Valentina
AU - Barilani, Mario
AU - Forloni, Gianluigi
AU - Perale, Giuseppe
AU - Lazzari, Lorenza
AU - Veglianese, Pietro
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Stem cell therapy with human mesenchymal stem cells (hMSCs) represents a promising strategy in spinal cord injury (SCI). However, both systemic and parenchymal hMSCs administrations show significant drawbacks as a limited number and viability of stem cells in situ. Biomaterials able to encapsulate and sustain hMSCs represent a viable approach to overcome these limitations potentially improving the stem cell therapy. In this study, we evaluate a new agarose/carbomer based hydrogel which combines different strategies to optimize hMSCs viability, density and delivery of paracrine factors. Specifically, we evaluate a new loading procedure on a lyophilized scaffold (soaked up effect) that reduces mechanical stress in encapsulating hMSCs into the hydrogel. In addition, we combine arginine-glycine-aspartic acid (RGD) tripeptide and 3D extracellular matrix deposition to increase the capacity to attach and maintain healthy hMSCs within the hydrogel over time. Furthermore, the fluidic diffusion from the hydrogel toward the injury site is improved by using a cling film that oriented efficaciously the delivery of paracrine factors in vivo. Finally, we demonstrate that an improved combination as here proposed of hMSCs and biomimetic hydrogel is able to immunomodulate significantly the pro-inflammatory environment in a SCI mouse model, increasing M2 macrophagic population and promoting a pro-regenerative environment in situ.
AB - Stem cell therapy with human mesenchymal stem cells (hMSCs) represents a promising strategy in spinal cord injury (SCI). However, both systemic and parenchymal hMSCs administrations show significant drawbacks as a limited number and viability of stem cells in situ. Biomaterials able to encapsulate and sustain hMSCs represent a viable approach to overcome these limitations potentially improving the stem cell therapy. In this study, we evaluate a new agarose/carbomer based hydrogel which combines different strategies to optimize hMSCs viability, density and delivery of paracrine factors. Specifically, we evaluate a new loading procedure on a lyophilized scaffold (soaked up effect) that reduces mechanical stress in encapsulating hMSCs into the hydrogel. In addition, we combine arginine-glycine-aspartic acid (RGD) tripeptide and 3D extracellular matrix deposition to increase the capacity to attach and maintain healthy hMSCs within the hydrogel over time. Furthermore, the fluidic diffusion from the hydrogel toward the injury site is improved by using a cling film that oriented efficaciously the delivery of paracrine factors in vivo. Finally, we demonstrate that an improved combination as here proposed of hMSCs and biomimetic hydrogel is able to immunomodulate significantly the pro-inflammatory environment in a SCI mouse model, increasing M2 macrophagic population and promoting a pro-regenerative environment in situ.
KW - Extracellular matrix
KW - Human mesenchymal stem cells
KW - Hydrogels
KW - Inflammation
KW - Macrophages
KW - Spinal cord injury
UR - http://www.scopus.com/inward/record.url?scp=84946422632&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84946422632&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2015.10.024
DO - 10.1016/j.biomaterials.2015.10.024
M3 - Article
VL - 75
SP - 135
EP - 147
JO - Biomaterials
JF - Biomaterials
SN - 0142-9612
ER -