Pharmacological Preconditioning Improves the Viability and Proangiogenic Paracrine Function of Hydrogel-Encapsulated Mesenchymal Stromal Cells
The efficacy of cell therapy is limited by low retention and survival of transplanted cells in the target tissues. In this work, we hypothesize that pharmacological preconditioning with celastrol, a natural potent antioxidant, could improve the viability and functions of mesenchymal stromal cells (M...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2021/6663467 |
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| author | Francesco K. Touani Melanie Borie Feryel Azzi Dominique Trudel Nicolas Noiseux Shant Der Sarkissian Sophie Lerouge |
| author_facet | Francesco K. Touani Melanie Borie Feryel Azzi Dominique Trudel Nicolas Noiseux Shant Der Sarkissian Sophie Lerouge |
| author_sort | Francesco K. Touani |
| collection | DOAJ |
| description | The efficacy of cell therapy is limited by low retention and survival of transplanted cells in the target tissues. In this work, we hypothesize that pharmacological preconditioning with celastrol, a natural potent antioxidant, could improve the viability and functions of mesenchymal stromal cells (MSC) encapsulated within an injectable scaffold. Bone marrow MSCs from rat (rMSC) and human (hMSC) origin were preconditioned for 1 hour with celastrol 1 μM or vehicle (DMSO 0.1% v/v), then encapsulated within a chitosan-based thermosensitive hydrogel. Cell viability was compared by alamarBlue and live/dead assay. Paracrine function was studied first by quantifying the proangiogenic growth factors released, followed by assessing scratched HUVEC culture wound closure velocity and proliferation of HUVEC when cocultured with encapsulated hMSC. In vivo, the proangiogenic activity was studied by evaluating the neovessel density around the subcutaneously injected hydrogel after one week in rats. Preconditioning strongly enhanced the viability of rMSC and hMSC compared to vehicle-treated cells, with 90% and 75% survival versus 36% and 58% survival, respectively, after 7 days in complete media and 80% versus 64% survival for hMSC after 4 days in low serum media (p<0.05). Celastrol-treated cells increased quantities of proangiogenic cytokines compared to vehicle-pretreated cells, with a significant 3.0-fold and 1.8-fold increase of VEGFa and SDF-1α, respectively (p<0.05). The enhanced paracrine function of preconditioned MSC was demonstrated by accelerated growth and wound closure velocity of injured HUVEC monolayer (p<0.05) in vitro. Moreover, celastrol-treated cells, but not vehicle-treated cells, led to a significant increase of neovessel density in the peri-implant region after one week in vivo compared to the control (blank hydrogel). These results suggest that combining cell pretreatment with celastrol and encapsulation in hydrogel could potentiate MSC therapy for many diseases, benefiting particularly ischemic diseases. |
| format | Article |
| id | doaj-art-c58abe62e2344f8280680cf6e4bf86b7 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-c58abe62e2344f8280680cf6e4bf86b72025-02-03T01:04:19ZengWileyStem Cells International1687-966X1687-96782021-01-01202110.1155/2021/66634676663467Pharmacological Preconditioning Improves the Viability and Proangiogenic Paracrine Function of Hydrogel-Encapsulated Mesenchymal Stromal CellsFrancesco K. Touani0Melanie Borie1Feryel Azzi2Dominique Trudel3Nicolas Noiseux4Shant Der Sarkissian5Sophie Lerouge6Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC, CanadaCentre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC, CanadaCentre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC, CanadaCentre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC, CanadaCentre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC, CanadaCentre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC, CanadaCentre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC, CanadaThe efficacy of cell therapy is limited by low retention and survival of transplanted cells in the target tissues. In this work, we hypothesize that pharmacological preconditioning with celastrol, a natural potent antioxidant, could improve the viability and functions of mesenchymal stromal cells (MSC) encapsulated within an injectable scaffold. Bone marrow MSCs from rat (rMSC) and human (hMSC) origin were preconditioned for 1 hour with celastrol 1 μM or vehicle (DMSO 0.1% v/v), then encapsulated within a chitosan-based thermosensitive hydrogel. Cell viability was compared by alamarBlue and live/dead assay. Paracrine function was studied first by quantifying the proangiogenic growth factors released, followed by assessing scratched HUVEC culture wound closure velocity and proliferation of HUVEC when cocultured with encapsulated hMSC. In vivo, the proangiogenic activity was studied by evaluating the neovessel density around the subcutaneously injected hydrogel after one week in rats. Preconditioning strongly enhanced the viability of rMSC and hMSC compared to vehicle-treated cells, with 90% and 75% survival versus 36% and 58% survival, respectively, after 7 days in complete media and 80% versus 64% survival for hMSC after 4 days in low serum media (p<0.05). Celastrol-treated cells increased quantities of proangiogenic cytokines compared to vehicle-pretreated cells, with a significant 3.0-fold and 1.8-fold increase of VEGFa and SDF-1α, respectively (p<0.05). The enhanced paracrine function of preconditioned MSC was demonstrated by accelerated growth and wound closure velocity of injured HUVEC monolayer (p<0.05) in vitro. Moreover, celastrol-treated cells, but not vehicle-treated cells, led to a significant increase of neovessel density in the peri-implant region after one week in vivo compared to the control (blank hydrogel). These results suggest that combining cell pretreatment with celastrol and encapsulation in hydrogel could potentiate MSC therapy for many diseases, benefiting particularly ischemic diseases.http://dx.doi.org/10.1155/2021/6663467 |
| spellingShingle | Francesco K. Touani Melanie Borie Feryel Azzi Dominique Trudel Nicolas Noiseux Shant Der Sarkissian Sophie Lerouge Pharmacological Preconditioning Improves the Viability and Proangiogenic Paracrine Function of Hydrogel-Encapsulated Mesenchymal Stromal Cells Stem Cells International |
| title | Pharmacological Preconditioning Improves the Viability and Proangiogenic Paracrine Function of Hydrogel-Encapsulated Mesenchymal Stromal Cells |
| title_full | Pharmacological Preconditioning Improves the Viability and Proangiogenic Paracrine Function of Hydrogel-Encapsulated Mesenchymal Stromal Cells |
| title_fullStr | Pharmacological Preconditioning Improves the Viability and Proangiogenic Paracrine Function of Hydrogel-Encapsulated Mesenchymal Stromal Cells |
| title_full_unstemmed | Pharmacological Preconditioning Improves the Viability and Proangiogenic Paracrine Function of Hydrogel-Encapsulated Mesenchymal Stromal Cells |
| title_short | Pharmacological Preconditioning Improves the Viability and Proangiogenic Paracrine Function of Hydrogel-Encapsulated Mesenchymal Stromal Cells |
| title_sort | pharmacological preconditioning improves the viability and proangiogenic paracrine function of hydrogel encapsulated mesenchymal stromal cells |
| url | http://dx.doi.org/10.1155/2021/6663467 |
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