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World J Stem Cells. Sep 26, 2014; 6(4): 448-457
Published online Sep 26, 2014. doi: 10.4252/wjsc.v6.i4.448
Kallikrein-kinin in stem cell therapy
Julie Chao, Grant Bledsoe, Lee Chao
Julie Chao, Grant Bledsoe, Lee Chao, Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, United States
Author contributions: Chao J reviewed the literature, conceived the paper and wrote the paper; Bledsoe G reviewed the literature, conceived the paper and wrote the paper; Chao L reviewed the literature, conceived the paper and wrote the paper.
Supported by National Institutes of Health, No. HL118516, HL29397 and HL44083
Correspondence to: Julie Chao, PhD, Professor, Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 173 Ashley Ave, Charleston, SC 29425, United States. chaoj@musc.edu
Telephone: +1-843-7929927 Fax: +1-843-7924850
Received: July 22, 2014
Revised: August 27, 2014
Accepted: August 30, 2014
Published online: September 26, 2014
Abstract

The tissue kallikrein-kinin system exerts a wide spectrum of biological activities in the cardiovascular, renal and central nervous systems. Tissue kallikrein-kinin modulates the proliferation, viability, mobility and functional activity of certain stem cell populations, namely mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs), mononuclear cell subsets and neural stem cells. Stimulation of these stem cells by tissue kallikrein-kinin may lead to protection against renal, cardiovascular and neural damage by inhibiting apoptosis, inflammation, fibrosis and oxidative stress and promoting neovascularization. Moreover, MSCs and EPCs genetically modified with tissue kallikrein are resistant to hypoxia- and oxidative stress-induced apoptosis, and offer enhanced protective actions in animal models of heart and kidney injury and hindlimb ischemia. In addition, activation of the plasma kallikrein-kinin system promotes EPC recruitment to the inflamed synovium of arthritic rats. Conversely, cleaved high molecular weight kininogen, a product of plasma kallikrein, reduces the viability and vasculogenic activity of EPCs. Therefore, kallikrein-kinin provides a new approach in enhancing the efficacy of stem cell therapy for human diseases.

Keywords: Tissue kallikrein, Plasma kallikrein, Kinin, Mesenchymal stem cells, Endothelial progenitor cells, Neural stem cells, Heart, Kidney, Brain

Core tip: Tissue kallikrein-kinin exerts beneficial actions in the cardiovascular, renal and central nervous systems. Recent studies demonstrated that genetic modification of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) by tissue kallikrein provides enhanced protection against renal ischemia/reperfusion, lupus nephritis, myocardial infarction and hindlimb ischemia. Tissue kallikrein stimulates the proliferation, viability, migration and functional activity of cultured MSCs, EPCs and neural stem cells. Moreover, plasma kallikrein-kinin augments EPC mobility and function in arthritis, whereas the cleaved kininogen product of plasma kallikrein inhibits EPC viability and tube formation. Thus, kallikrein-kinin may enhance the efficacy of stem cell therapy for human diseases.