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Novel Gene-Modified Mesenchymal Stem Cell Therapy Reverses Impaired Wound Healing in Ischemic Limbs.
- Source :
- Annals of Surgery; Sep2023, Vol. 278 Issue 3, p383-395, 13p
- Publication Year :
- 2023
-
Abstract
- Objective: Here, we report a new method to increase the therapeutic potential of mesenchymal stem/stromal cells (MSCs) for ischemic wound healing. We tested biological effects of MSCs modified with E-selectin, a cell adhesion molecule capable of inducing postnatal neovascularization, on a translational murine model. Background: Tissue loss significantly worsens the risk of extremity amputation for patients with chronic limb-threatening ischemia. MSC-based therapeutics hold major promise for wound healing and therapeutic angiogenesis, but unmodified MSCs demonstrate only modest benefits. Methods: Bone marrow cells harvested from FVB/ROSA26Sor<superscript>mTmG</superscript> donor mice were transduced with E-selectin-green fluorescent protein (GFP)/AAV-DJ or GFP/AAV-DJ (control). Ischemic wounds were created via a 4 mm punch biopsy in the ipsilateral limb after femoral artery ligation in recipient FVB mice and subsequently injected with phosphate-buffered saline or 1×10<superscript>6</superscript> donor MSC<superscript>GFP</superscript> or MSC<superscript>E-selectin-GFP</superscript>. Wound closure was monitored daily for 7 postoperative days, and tissues were harvested for molecular and histologic analysis and immunofluorescence. Whole-body DiI perfusion and confocal microscopy were utilized to evaluate wound angiogenesis. Results: Unmodified MSCs do not express E-selectin, and MSC<superscript>E-selectin-GFP</superscript> gain stronger MSC phenotype yet maintain trilineage differentiation and colony-forming capability. MSC<superscript>E-selectin-GFP</superscript> therapy accelerates wound healing compared with MSC<superscript>GFP</superscript> and phosphate-buffered saline treatment. Engrafted MSC<superscript>E-selectin-GFP</superscript> manifest stronger survival and viability in wounds at postoperative day 7. Ischemic wounds treated with MSC<superscript>E-selectin-GFP</superscript> exhibit more abundant collagen deposition and enhanced angiogenic response. Conclusions: We establish a novel method to potentiate regenerative and proangiogenic capability of MSCs by modification with E-selectin/adeno-associated virus. This innovative therapy carries the potential as a platform worthy of future clinical studies. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00034932
- Volume :
- 278
- Issue :
- 3
- Database :
- Supplemental Index
- Journal :
- Annals of Surgery
- Publication Type :
- Academic Journal
- Accession number :
- 170751009
- Full Text :
- https://doi.org/10.1097/SLA.0000000000005949