Vascular regeneration and skeletal muscle repair induced by long-term exposure to SDF-1α derived from engineered mesenchymal stem cells after hindlimb ischemia
2
조회
0
다운로드
0
인용
0
참고문헌
초록
Despite recent progress in medical and endovascular therapy, the prognosis for patients with critical limb ischemia (CLI) remains poor. In response, various stem cells and growth factors have been assessed for use in therapeutic neovascularization and limb salvage in CLI patients. However, the clinical outcomes of cell-based therapeutic angiogenesis have not provided the promised benefits, reinforcing the need for novel cell-based therapeutic angiogenic strategies to cure untreatable CLI. In the present study, we investigated genetically engineered mesenchymal stem cells (MSCs) derived from human bone marrow that continuously secrete stromal-derived factor-1α (SDF1α-eMSCs) and demonstrated that intramuscular injection of SDF1α-eMSCs can provide long-term paracrine effects in limb ischemia and effectively contribute to vascular regeneration as well as skeletal muscle repair through increased phosphorylation of ERK and Akt within the SDF1α/CXCR4 axis. These results provide compelling evidence that genetically engineered MSCs with SDF-1α can be an effective strategy for successful limb salvage in limb ischemia.
Abstract
Despite recent progress in medical and endovascular therapy, the prognosis for patients with critical limb ischemia (CLI) remains poor. In response, various stem cells and growth factors have been assessed for use in therapeutic neovascularization and limb salvage in CLI patients. However, the clinical outcomes of cell-based therapeutic angiogenesis have not provided the promised benefits, reinforcing the need for novel cell-based therapeutic angiogenic strategies to cure untreatable CLI. In the present study, we investigated genetically engineered mesenchymal stem cells (MSCs) derived from human bone marrow that continuously secrete stromal-derived factor-1α (SDF1α-eMSCs) and demonstrated that intramuscular injection of SDF1α-eMSCs can provide long-term paracrine effects in limb ischemia and effectively contribute to vascular regeneration as well as skeletal muscle repair through increased phosphorylation of ERK and Akt within the SDF1α/CXCR4 axis. These results provide compelling evidence that genetically engineered MSCs with SDF-1α can be an effective strategy for successful limb salvage in limb ischemia.
참고문헌 (30)
- Teraa, M., "Critical Limb Ischemia : Current Trends and Future Directions", J. Am. Heart Assoc, 5, pp.e002938~ (2016)
- Tu, C., "Nanoscale strategies: treatment for peripheral vascular disease and critical limb ischemia", ACS Nano, 9, pp.3436~3452 (2015)
- Thorud, J. C., "Mortality after nontraumatic major amputation among patients with diabetes and peripheral vascular disease : a systematic review", J Foot Ankle Surg, 55, pp.591~599 (2016)
- Golomb, B. A., "Peripheral arterial disease", Circulation, 114, pp.688~699 (2006)
- Jaluvka, F., "Current Status of Cell-Based Therapy in Patients with Critical Limb Ischemia", Int. J. Mol. Sci, 21, pp.8999~ (2020)
- Swaminathan, A., "Lower extremity amputation in peripheral artery disease : improving patient outcomes", Vasc. Health Risk Manag, 10, pp.417~424 (2014)
- McDermott, M. M., "Skeletal muscle pathology in peripheral artery disease", Arterioscler. Thromb. Vasc. Biol, 40, pp.2577~2585 (2020)
- Han, J., "Therapeutic angiogenesis-based strategy for peripheral artery disease", Theranostics, 12, pp.5015~5033 (2022)
- Ferrari, R., "Inflammatory caspase activity mediates HMGB1 release and differentiation in myoblasts affected by peripheral arterial disease", Cells, 11, pp.1163~ (2022)
- Jazwa, A., "Limb ischemia and vessel regeneration: is there a role for VEGF?", Vascul. Pharmacol, 86, pp.18~30 (2016)
- Grochot-Przeczek, A., "Therapeutic angiogenesis for revascularization in peripheral artery disease", Gene, 525, pp.220~228 (2013)
- Lau, T. T., "Stromal cell-derived factor-1 (SDF-1): homing factor for engineered regenerative medicine", Expert Opin. Biol. Ther, 11, pp.189~197 (2011)
- Shi, Y., "The role of the CXCL12", CXCR4, Front Pharmacol, pp.2020, 11[DOI]
- Brzoska, E., "Sdf-1(CXCL12)improves skeletal muscle regeneration via the mobilisation of Cxcr4 and CD34 expressing cells", Biol Cell, 104, pp.722~737 (2012)
- Stratman, A. N., "Chemokine mediated signalling within arteries promotes vascular smooth muscle cell recruitment", Commun Biol, 3, pp.734~ (2020)
- Zhang, H., "SDF1", CXCR4 axis plays a role in angiogenesis during the degeneration of intervertebral discs, 2019, pp.20, 1203~1211
- Kuliszewski, M. A., "Vascular gene transfer of SDF-1 promotes endothelial progenitor cell engraftment and enhances angiogenesis in ischemic muscle", Mol. Ther, 19, pp.895~902 (2011)
- Shams, A. S., "The chemokine receptor CXCR4 regulates satellite cell activation, early expansion, and self-renewal, in response to skeletal muscle injury", Front Cell Dev Biol, 10 (2022)
- Bromage, D. I., "Stromal derived factor 1α : a chemokine that delivers a two-pronged defence of the myocardium", Pharmacol. Ther, 143, pp.305~315 (2014)
- Baldo, B. A., "Side effects of cytokines approved for therapy", Drug Saf, 37, pp.921~943 (2014)
- Kim Hyeok, "Enhancement strategy for effective vascular regeneration following myocardial infarction through a dual stem cell approach", Experimental and Molecular Medicine, 54, pp.1~14 (2022), 생화학분자생물학회[DOI]
- Lavoie, H., "ERK signalling : a master regulator of cell behaviour, life and fate", Nat. Rev. Mol Cell Biol, 21, pp.607~632 (2020)
- Laumonier, T., "Muscle injuries and strategies for improving their repair", J. Exp. Orthop, 3, pp.15~ (2016)
- Choi, S., "Cellular dynamics of myogenic cell migration : molecular mechanisms and implications for skeletal muscle cell therapies", EMBO Mol. Med, 12, pp.e12357~ (2020)
- Lee, J. J., "Systematic interrogation of angiogenesis in the ischemic mouse hind limb", Arterioscler. Thromb. Vasc. Biol, 40, pp.2454~2467 (2020)
- Annex, B. H., "Therapeutic angiogenesis for critical limb ischaemia", Nat. Rev. Cardiol, 10, pp.387~396 (2013)
- Chakravarthy, M. V., "Insulin-like growth Factor-I extends in vitroreplicative life span of skeletal muscle satellite cells by enhancing G1", S cell cycle progression via the activation of phosphatidylinositol 3′-Kinase, J. Biol. Chem, pp.2000, 275[DOI]
- Giri, J., "CCL2 and CXCL12 derived from mesenchymal stromal cells cooperatively polarize IL-10+ tissue macrophages to mitigate gut injury", Cell Rep, 30, pp.1923~1934 (2020)
- Hickey, K. N., "Stromal cell-derived Factor-1a autocrine", paracrine signaling contributes to spatiotemporal gradients in the brain, 2021, pp.14, 75~87
- Levine, S. J, "Molecular mechanisms of soluble cytokine receptor generation", J. Biol. Chem, 283, pp.14177~14181 (2008)