Angela Park1, Juliana Barrera-Ramirez1, Indee Ranasinghe1, Sophie Pilon1, Richmond Sy2,3, Dean Fergusson2, David S Allan4,5,6. 1. Regenerative Medicine Program, Ottawa Hospital Research Institute, 501 Smyth Rd, Box 704, Ottawa, ON, K1H 8L6, Canada. 2. Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada. 3. Department of Medicine, University of Ottawa, Ottawa, ON, Canada. 4. Regenerative Medicine Program, Ottawa Hospital Research Institute, 501 Smyth Rd, Box 704, Ottawa, ON, K1H 8L6, Canada. daallan@ohri.ca. 5. Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada. daallan@ohri.ca. 6. Department of Medicine, University of Ottawa, Ottawa, ON, Canada. daallan@ohri.ca.
Abstract
BACKGROUND: Mesenchymal stromal cells (MSCs) and endothelial progenitor cells (EPCs) are used in cell-based regenerative therapy. HMG CoA reductase inhibitors (statins) appear promising in blocking apoptosis, prolonging progenitor cell survival and improving their capacity to repair organ function. METHODS: We performed a systematic review of preclinical and clinical studies to clarify whether statins can improve cell-based repair of organ injury. MEDLINE, EMBASE, and PUBMED databases were searched (1947 to June 25, 2013). Controlled clinical and pre-clinical studies were included that evaluated statin therapy used alone or in combination with MSCs or EPCs in patients or animals with organ injury. RESULTS: After screening 771 citations, 100 records underwent full eligibility screening of which 38 studies met eligibility and were included in the review: Studies were grouped into pre-clinical studies that involved statin treatment in combination with cell therapy (18 studies), preclinical studies of statin therapy alone (13 studies) and clinical studies of statin therapy (7 studies). Studies addressed cardiac injury (14 studies), vascular disorders (15 studies), neurologic conditions (8 studies) and bone fractures (1 study). Pre-clinical studies of statins in combination with MSC infusion (15 studies) or EPC therapy (3 studies) were described and despite marked heterogeneity in reporting outcomes of cellular analysis and organ function, all of these cell-based pre-clinical studies reported improved organ recovery with the addition of statin therapy. Moreover, 13 pre-clinical studies involved the administration of a statin drug alone to animals. An increase in EPC number and/or function (no studies of MSCs) was reported in 11 of these studies (85 %) and improved organ function in 12 studies (92 %). We also identified 7 clinical studies and none involved the administration of cells but described an increased number and/or function of EPCs (no studies of MSCs) and improved organ function with statin therapy (1.2-fold to 35-fold improvement over controls) in all 7 studies. CONCLUSION: Our systematic review provides a foundation of encouraging results that support further study of statins in regenerative therapy to augment the number and/or function of MSCs used in cell-based repair and to augment the number and function of EPCs in vivo to repair damaged tissues. Larger studies are needed to ensure safety and confirm clinical benefits.
BACKGROUND: Mesenchymal stromal cells (MSCs) and endothelial progenitor cells (EPCs) are used in cell-based regenerative therapy. HMG CoA reductase inhibitors (statins) appear promising in blocking apoptosis, prolonging progenitor cell survival and improving their capacity to repair organ function. METHODS: We performed a systematic review of preclinical and clinical studies to clarify whether statins can improve cell-based repair of organ injury. MEDLINE, EMBASE, and PUBMED databases were searched (1947 to June 25, 2013). Controlled clinical and pre-clinical studies were included that evaluated statin therapy used alone or in combination with MSCs or EPCs in patients or animals with organ injury. RESULTS: After screening 771 citations, 100 records underwent full eligibility screening of which 38 studies met eligibility and were included in the review: Studies were grouped into pre-clinical studies that involved statin treatment in combination with cell therapy (18 studies), preclinical studies of statin therapy alone (13 studies) and clinical studies of statin therapy (7 studies). Studies addressed cardiac injury (14 studies), vascular disorders (15 studies), neurologic conditions (8 studies) and bone fractures (1 study). Pre-clinical studies of statins in combination with MSC infusion (15 studies) or EPC therapy (3 studies) were described and despite marked heterogeneity in reporting outcomes of cellular analysis and organ function, all of these cell-based pre-clinical studies reported improved organ recovery with the addition of statin therapy. Moreover, 13 pre-clinical studies involved the administration of a statin drug alone to animals. An increase in EPC number and/or function (no studies of MSCs) was reported in 11 of these studies (85 %) and improved organ function in 12 studies (92 %). We also identified 7 clinical studies and none involved the administration of cells but described an increased number and/or function of EPCs (no studies of MSCs) and improved organ function with statin therapy (1.2-fold to 35-fold improvement over controls) in all 7 studies. CONCLUSION: Our systematic review provides a foundation of encouraging results that support further study of statins in regenerative therapy to augment the number and/or function of MSCs used in cell-based repair and to augment the number and function of EPCs in vivo to repair damaged tissues. Larger studies are needed to ensure safety and confirm clinical benefits.
Authors: Martin Steinmetz; Bastian Pelster; Eva Lucanus; Jean Francois Arnal; Georg Nickenig; Nikos Werner Journal: J Mol Cell Cardiol Date: 2013-01-04 Impact factor: 5.000
Authors: Carmen G Palii; Branka Vulesevic; Sylvain Fraineau; Erinija Pranckeviciene; Alexander J Griffith; Alphonse Chu; Hervé Faralli; Yuhua Li; Brian McNeill; Jie Sun; Theodore J Perkins; F Jeffrey Dilworth; Carol Perez-Iratxeta; Erik J Suuronen; David S Allan; Marjorie Brand Journal: Cell Stem Cell Date: 2014-05-01 Impact factor: 24.633
Authors: Ulf Landmesser; Niels Engberding; Ferdinand H Bahlmann; Arnd Schaefer; Antje Wiencke; Andre Heineke; Stephan Spiekermann; Denise Hilfiker-Kleiner; Christian Templin; Daniel Kotlarz; Maja Mueller; Martin Fuchs; Burkhard Hornig; Hermann Haller; Helmut Drexler Journal: Circulation Date: 2004-10-05 Impact factor: 29.690
Authors: J Shepherd; S M Cobbe; I Ford; C G Isles; A R Lorimer; P W MacFarlane; J H McKillop; C J Packard Journal: N Engl J Med Date: 1995-11-16 Impact factor: 91.245
Authors: A Adamičková; A Gažová; M Adamička; N Chomaničová; S Valašková; Z Červenák; B Šalingová; J Kyselovič Journal: Physiol Res Date: 2021-12-30 Impact factor: 2.139
Authors: Velia Cassano; Giovanni Tripepi; Maria Perticone; Sofia Miceli; Irene Scopacasa; Giuseppe Armentaro; Marta Greco; Raffaele Maio; Marta Letizia Hribal; Giorgio Sesti; Francesco Perticone; Angela Sciacqua Journal: Hypertens Res Date: 2021-09-01 Impact factor: 3.872