The role of the tumor suppressor gene NDRG2 in angiogenesis and wound healing
Final Report Abstract
We have demonstrated that downregulation and knockout of NDRG2 in DCs significantly increases the secretion of VEGF from DCs, thus enabling these cells to promote angiogenesis and tissue regeneration. Based on these findings, we have developed a novel cell-based therapy for wound healing by seeding genetically engineered DCs on pullulan-collagen hydrogels and thereby were able to accomplish significantly faster healing rates compared to wildtype cells. Since clinical-grade manufacturing of autologous DCs for adoptive cell transfer is already well established in clinical practice and DC immunotherapy is already being used in multiple clinical trials, we believe that genetically edited DCs have a high potential for successful clinical translation as a cell-based therapy for patients suffering from complex wounds that are refractive to treatment with the current standard of care. In future clinical applications, DC harvest could easily be performed from standard blood samples obtained at wound clinics, without the need for tissue biopsies or other surgical interventions. In summary, our genetically edited DC therapy provides a highly effective, robust, and ready-to-use approach for the treatment of chronic wounds. It provides strong evidence towards and opens the door for future clinical trials of DC therapy combined with gene editing. These findings may provide significant translational opportunities to help patients with diabetic and non-diabetic ulcers.
Publications
- Abstract 111: Adoptive Transfer Of Tolerogenic Dendritic Cells Promotes Angiogenesis And Wound Healing. Plast Reconstr Surg Glob Open. 2020;8(4 Suppl):73-74. Published 2020 May 13
Henn D, Bonham CA Jr., Chen K, et al.
(See online at https://doi.org/10.1097/01.GOX.0000667500.37011.55) - CRISPR/Cas9 Editing of Autologous Dendritic Cells to Enhance Angiogenesis and Wound Healing. Jahrestagung des Plastic Surgery Research Council, August 2020
Henn, D
- CRISPR/Cas9 Editing of Autologous Dendritic Cells to Induce Wound Healing. Jahrestagung der Wound Healing Society, Mai 2021
Henn, D
- QS3: CRISPR/Cas9 Editing of Autologous Dendritic Cells to Enhance Angiogenesis and Wound Healing. Plast Reconstr Surg Glob Open. 2021;9(7 Suppl):7
Henn D, Zhao D, Bonham CA Jr., et al.
(See online at https://doi.org/10.1097/01.GOX.0000769960.21263.cc) - Cas9-Mediated Knockout of Ndrg2 Enhances the Regenerative Potential of Dendritic Cells for Wound Healing
Henn D, Zhao D, Chen K, Trotsyuk A, Bonham CA, Fischer KS, Kehl T, Fehlmann T, Sivaraj D, Greco AH, Moortgat Illouz SE, Padmanabhan J, Barrera JA, Kneser U, Lenhof HP, Januszyk M, Levi B, Keller A, Longaker MT, Qi LS, Gurtner GC
(See online at https://doi.org/10.1101/2022.03.14.484360)
