Culture-Modified Bone Marrow Cells Attenuate Cardiac and Renal Injury in a Chronic Kidney Disease Rat Model via a Novel Antifibrotic Mechanism
Darren A Yuen, Kim A Connelly, Andrew Advani, Christine Liao, Michael A Kuliszewski, Judy Trogadis, Kerri Thai, Suzanne L Advani, Yuan Zhang, Darren J Kelly, Howard Leong-Poi, Armand Keating, Philip A Marsden, Duncan J Stewart, Richard E Gilbert
PLOS ONE | PUBLIC LIBRARY SCIENCE | Published : 2010
BACKGROUND: Most forms of chronic kidney disease are characterized by progressive renal and cardiac fibrosis leading to dysfunction. Preliminary evidence suggests that various bone marrow-derived cell populations have antifibrotic effects. In exploring the therapeutic potential of bone marrow derived cells in chronic cardio-renal disease, we examined the anti-fibrotic effects of bone marrow-derived culture modified cells (CMCs) and stromal cells (SCs). METHODOLOGY/PRINCIPAL FINDINGS: In vitro, CMC-conditioned medium, but not SC-conditioned medium, inhibited fibroblast collagen production and cell signalling in response to transforming growth factor-beta. The antifibrotic effects of CMCs and ..View full abstract
This work was supported by grants from the Canadian Institutes of Health Research (CIHR) and the Physicians' Services Incorporated Foundation of Ontario. Dr. Yuen is supported by a KRESCENT postdoctoral fellowship. Dr. Gilbert is supported by a generous donation from George and Diane Mara. Dr. Connelly is supported by a Clinician Scientist award from the Heart and Stroke Foundation of Ontario. Dr. Advani is supported by a Clinician Scientist award from the Canadian Diabetes Association. Dr. Leong- Poi is supported by a Phase II Clinician Scientist Award from the Heart and Stroke Foundation of Ontario and an Early Researcher Award from the Ministry of Research and Innovation, Ontario, Canada. Dr. Keating holds the Gloria and Seymour Epstein Chair in Cell Therapy and Transplantation at the University Health Network and the University of Toronto. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.