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Use of Statins to Augment Progenitor Cell Function in Preclinical and Clinical Studies of Regenerative Therapy: a Systematic Review

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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.

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Acknowledgments

We wish to acknowledge the expertise and assistance of Risa Shorr from the library at The Ottawa Hospital for help with design and execution of the systematic search. Funding support for the project was provided by the Department of Medicine, University of Ottawa. We gratefully acknowledge support from Canadian Institutes of Health Research for a summer student award (SP) and a New Investigator Award (DSA) and support for a summer student research stipend from the Mach-Gaesslen Foundation of Canada (JBR). An endowed Chair in Clinical Epidemiology (DF) from the University of Ottawa (U of O) and Ottawa Hospital Research Institute is gratefully acknowledged. DSA is supported in part by the Department of Medicine at U of O. None of the authors have any conflicts of interest to declare.

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Authors and Affiliations

  1. Regenerative Medicine Program, Ottawa Hospital Research Institute, 501 Smyth Rd, Box 704, Ottawa, ON, K1H 8L6, Canada

    Angela Park, Juliana Barrera-Ramirez, Indee Ranasinghe, Sophie Pilon & David S. Allan

  2. Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada

    Richmond Sy, Dean Fergusson & David S. Allan

  3. Department of Medicine, University of Ottawa, Ottawa, ON, Canada

    Richmond Sy & David S. Allan

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  1. Angela Park
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Correspondence to David S. Allan.

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Park, A., Barrera-Ramirez, J., Ranasinghe, I. et al. Use of Statins to Augment Progenitor Cell Function in Preclinical and Clinical Studies of Regenerative Therapy: a Systematic Review. Stem Cell Rev and Rep 12, 327–339 (2016). https://doi.org/10.1007/s12015-016-9647-7

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