267 Original Paper Cell Physiol Biochem 2011;28:267-278 Accepted: May 16, 2011 Cellular Physiology Cellular Physiology Cellular Physiology Cellular Physiology Cellular Physiology and Biochemistr and Biochemistr and Biochemistr and Biochemistr and Biochemistry Copyright © 2011 S. Karger AG, Basel Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com © 2011 S. Karger AG, Basel 1015-8987/11/0282-0267$38.00/0 Accessible online at: www.karger.com/cpb Paracrine Interaction between Bone Marrow- derived Stem Cells and Renal Epithelial Cells Rafael S. Lindoso 1,2 , Dayana S. Araujo 1,2 , Juliana Adão-Novaes 1,3 , Rafael M. Mariante 1,3 , Karine S. Verdoorn 1,2 , Lucianne Fragel- Madeira 3,4 , Celso Caruso-Neves 1,2 , Rafael Linden 1,3 , Adalberto Vieyra 1,2 and Marcelo Einicker-Lamas 1,2 1 Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, 2 National Institute of Science and Technology for Structural Biology and Bioimaging, Rio de Janeiro, 3 National Institute of Science and Technology for Gene Therapy, Rio de Janeiro, 4 Institute of Biology, Fluminense Federal University, Niterói Marcelo Einicker-Lamas Institute of Biophysics Carlos Chagas Filho Federal University of Rio de Janeiro, Rio de Janeiro 21941-902 (Brazil) Tel. + 55 21 2562 6521, Fax + 55 21 2280 8193 E-Mail einicker@biof.ufrj.br Key Words Bone marrow-derived cells • Mesenchymal stem cells • Metabolic stress • Paracrine interactions Abstract Background/Aims: Renal tubular cells are the main target of ischemic insult associated with acute renal injury. Low oxygen and nutrient supplies result in ATP depletion, leading to cell death and loss of renal function. A possible mechanism by which bone marrow-derived cells support renal tissue regeneration relies on the capacity of mononuclear cells (BMMC), particularly mesenchymal stem cells (MSC), to secrete paracrine factors that mediate support for kidney regeneration. Methods: BMMC/ MSC and renal cells (LLC-PK 1 from pig and IRPTC from rat) were co-cultured under stressful conditions (ATP depletion and/or serum free starvation), physically separated by a microporous membrane (0.4 μm), was used to determine whether bone marrow-derived cells can interact with renal cells in a paracrine manner. Results: This interaction resulted in stimulation of renal cell proliferation and the arrest of cell death. MSC elicit effective responses in renal cells in terms of stimulating proliferation and protection. Such effects are observed in renal cells co-cultured with rat BMMC/MSC, an indication that paracrine mechanisms are not entirely species- specific. Conclusion: The paracrine action of BMMC/ MSC was influenced by a renal cell stimulus released during stress, indicating that cross-talk with injured cells is required for renal regeneration supported by bone marrow-derived cells. Introduction Adult stem cells play a key role in kidney tissue regeneration, replacing cells lost through injury [1]. Among several other events, cytokines and growth factors secreted into the blood by injured renal tissue mobilize bone marrow stem cells to the affected regions, thereby modulating kidney repair and regenerative responses [2- 4]. These processes aid the restoration of tissue architecture and the reestablishment of renal function [5]. Although a role for bone marrow mononuclear cells (BMMC) in renal injuries is well established, the