Macromolecular Crowding Supports the Generation of Basal Membrane-Rich Pericyte-Based Cell Sheets Useful for Cell Therapy of Diabetic Wounds
Diabetic foot ulcers (DFUs) are associated with a high risk of amputations and a 50% 5-year survival rate due at least in part to the limited angiogenic and wound healing capacity of patients with diabetes. Cell therapy via intramuscular injection of peripheral blood mononuclear cells showed encoura...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2025-03-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.1177/09636897241309698 |
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| author | Andrea Rampin Carlo Maria Ferdinando Caravaggi Luigi Troisi Gaia Spinetti |
| author_facet | Andrea Rampin Carlo Maria Ferdinando Caravaggi Luigi Troisi Gaia Spinetti |
| author_sort | Andrea Rampin |
| collection | DOAJ |
| description | Diabetic foot ulcers (DFUs) are associated with a high risk of amputations and a 50% 5-year survival rate due at least in part to the limited angiogenic and wound healing capacity of patients with diabetes. Cell therapy via intramuscular injection of peripheral blood mononuclear cells showed encouraging but limited results. Such limitations may arise from the limited ability of therapeutic cells to adhere to the target tissue. The development of a methodology able to support the targeted delivery of viable angiogenic cells would improve cell therapy outcomes in DFU. Here, we optimized a protocol for the production of autologous extracellular matrix (ECM)-rich pericyte-based cell sheets for cell delivery. Pericytes were isolated from skeletal muscle biopsies of DFU patients and non-diabetic controls and characterized by flow cytometry and immunofluorescence. Human umbilical vein endothelial cells used for the optimization of collagen IV deposition showed a positive correlation with seeding density and a negative one with sub-culture passaging ( P < 0.05). Macromolecular crowding significantly increased collagen IV deposition both in human umbilical vein endothelial cells and in patient-derived pericytes ( P < 0.01) without affecting proliferation ( P > 0.05). Finally, DFU patient-derived pericytes effectively deposited ECM supporting their use for autologous cell sheet production. |
| format | Article |
| id | doaj-art-192e1d2fa05a4ec1a21dca106159816b |
| institution | DOAJ |
| issn | 1555-3892 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj-art-192e1d2fa05a4ec1a21dca106159816b2025-08-20T02:57:35ZengSAGE PublishingCell Transplantation1555-38922025-03-013410.1177/09636897241309698Macromolecular Crowding Supports the Generation of Basal Membrane-Rich Pericyte-Based Cell Sheets Useful for Cell Therapy of Diabetic WoundsAndrea Rampin0Carlo Maria Ferdinando Caravaggi1Luigi Troisi2Gaia Spinetti3Cardiovascular Research Unit, IRCCS MultiMedica, Milan, ItalyDiabetic Foot Department, IRCCS MultiMedica, Milan, ItalyReconstructive Microsurgery Service – Department of Hand Surgery & Rehabilitation-IRCCS MultiMedica, Milan, ItalyCardiovascular Research Unit, IRCCS MultiMedica, Milan, ItalyDiabetic foot ulcers (DFUs) are associated with a high risk of amputations and a 50% 5-year survival rate due at least in part to the limited angiogenic and wound healing capacity of patients with diabetes. Cell therapy via intramuscular injection of peripheral blood mononuclear cells showed encouraging but limited results. Such limitations may arise from the limited ability of therapeutic cells to adhere to the target tissue. The development of a methodology able to support the targeted delivery of viable angiogenic cells would improve cell therapy outcomes in DFU. Here, we optimized a protocol for the production of autologous extracellular matrix (ECM)-rich pericyte-based cell sheets for cell delivery. Pericytes were isolated from skeletal muscle biopsies of DFU patients and non-diabetic controls and characterized by flow cytometry and immunofluorescence. Human umbilical vein endothelial cells used for the optimization of collagen IV deposition showed a positive correlation with seeding density and a negative one with sub-culture passaging ( P < 0.05). Macromolecular crowding significantly increased collagen IV deposition both in human umbilical vein endothelial cells and in patient-derived pericytes ( P < 0.01) without affecting proliferation ( P > 0.05). Finally, DFU patient-derived pericytes effectively deposited ECM supporting their use for autologous cell sheet production.https://doi.org/10.1177/09636897241309698 |
| spellingShingle | Andrea Rampin Carlo Maria Ferdinando Caravaggi Luigi Troisi Gaia Spinetti Macromolecular Crowding Supports the Generation of Basal Membrane-Rich Pericyte-Based Cell Sheets Useful for Cell Therapy of Diabetic Wounds Cell Transplantation |
| title | Macromolecular Crowding Supports the Generation of Basal Membrane-Rich Pericyte-Based Cell Sheets Useful for Cell Therapy of Diabetic Wounds |
| title_full | Macromolecular Crowding Supports the Generation of Basal Membrane-Rich Pericyte-Based Cell Sheets Useful for Cell Therapy of Diabetic Wounds |
| title_fullStr | Macromolecular Crowding Supports the Generation of Basal Membrane-Rich Pericyte-Based Cell Sheets Useful for Cell Therapy of Diabetic Wounds |
| title_full_unstemmed | Macromolecular Crowding Supports the Generation of Basal Membrane-Rich Pericyte-Based Cell Sheets Useful for Cell Therapy of Diabetic Wounds |
| title_short | Macromolecular Crowding Supports the Generation of Basal Membrane-Rich Pericyte-Based Cell Sheets Useful for Cell Therapy of Diabetic Wounds |
| title_sort | macromolecular crowding supports the generation of basal membrane rich pericyte based cell sheets useful for cell therapy of diabetic wounds |
| url | https://doi.org/10.1177/09636897241309698 |
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