Renal disease is a worldwide health issue. Besides transplantation, current therapies revolve around dialysis, which only delays disease progression but cannot replace other renal functions, such as synthesizing erythropoietin. To address these limitations, cell-based approaches have been proposed to restore damaged kidneys as an alternative to current therapies. Recent studies have shown that stem cell-derived secretomes can enhance tissue regeneration. However, many growth factors undergo rapid degradation when they are injected into the body in a soluble form. Efficient delivery and controlled release of secreting factors at the sites of injury would improve the efficacy in tissue regeneration. Herein, we developed a gel-based delivery system for controlled delivery of trophic factors in the conditioned medium (CM) secreted from human placental stem cells (HPSCs) and evaluated the effect of trophic factors on renal regeneration. CM treatment significantly enhanced cell proliferation and survival in vitro. Platelet-rich plasma (PRP) was used as a delivery vehicle for CM. Analysis of the release kinetics demonstrated that CM delivery through the PRP gel resulted in a controlled release of the factors both in vitro and in vivo. In an acute kidney injury model in rats, functional and structural analysis showed that CM delivery using the PRP gel system into the injured kidney minimized renal tissue damage, leading to a more rapid functional recovery when compared with saline, CM, or vehicle only injection groups. These results suggest that controlled delivery of HPSC-derived trophic factors may provide efficient repair of renal tissue injury. Stem Cells Translational Medicine 2019;8:959&970.
Bibliographical noteFunding Information:
We thank the Regenerative Medicine Clinical Center at Wake Forest Institute for Regenerative Medicine for the HPSC and also acknowledge the editorial work of Karen Klein, M.A., in the Wake Forest Clinical and Translational Science Institute (UL1 TR001420; PI: McClain), as well as Dr. Weling Zhao. This study was supported, in part, by a grant from the State of North Carolina.
© 2019 The Authors. Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press
All Science Journal Classification (ASJC) codes
- Developmental Biology
- Cell Biology