Controlled Delivery of Stem Cell-Derived Trophic Factors Accelerates Kidney Repair After Renal Ischemia-Reperfusion Injury in Rats

Hyung-Eun Yim, Doo Sang Kim, Hyun Chul Chung, Brian Shing, Kyung Hyun Moon, Sunil K. George, Michael W. Kim, Zachary Atala, Ji Hyun Kim, In Kap Ko, James J. Yoo

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)959-970
Number of pages12
JournalStem Cells Translational Medicine
Volume8
Issue number9
DOIs
Publication statusPublished - 2019 Jan 1

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Reperfusion Injury
Conditioned Culture Medium
Stem Cells
Kidney
Platelet-Rich Plasma
Regeneration
Gels
Translational Medical Research
Wounds and Injuries
Erythropoietin
Acute Kidney Injury
Disease Progression
Dialysis
Cell Survival
Intercellular Signaling Peptides and Proteins
Therapeutics
Transplantation
Cell Proliferation
Injections

Keywords

  • Acute kidney injury
  • Conditioned medium
  • Drug delivery systems
  • Kidney regeneration

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Cite this

Controlled Delivery of Stem Cell-Derived Trophic Factors Accelerates Kidney Repair After Renal Ischemia-Reperfusion Injury in Rats. / Yim, Hyung-Eun; Kim, Doo Sang; Chung, Hyun Chul; Shing, Brian; Moon, Kyung Hyun; George, Sunil K.; Kim, Michael W.; Atala, Zachary; Kim, Ji Hyun; Ko, In Kap; Yoo, James J.

In: Stem Cells Translational Medicine, Vol. 8, No. 9, 01.01.2019, p. 959-970.

Research output: Contribution to journalArticle

Yim, H-E, Kim, DS, Chung, HC, Shing, B, Moon, KH, George, SK, Kim, MW, Atala, Z, Kim, JH, Ko, IK & Yoo, JJ 2019, 'Controlled Delivery of Stem Cell-Derived Trophic Factors Accelerates Kidney Repair After Renal Ischemia-Reperfusion Injury in Rats', Stem Cells Translational Medicine, vol. 8, no. 9, pp. 959-970. https://doi.org/10.1002/sctm.18-0222
Yim, Hyung-Eun ; Kim, Doo Sang ; Chung, Hyun Chul ; Shing, Brian ; Moon, Kyung Hyun ; George, Sunil K. ; Kim, Michael W. ; Atala, Zachary ; Kim, Ji Hyun ; Ko, In Kap ; Yoo, James J. / Controlled Delivery of Stem Cell-Derived Trophic Factors Accelerates Kidney Repair After Renal Ischemia-Reperfusion Injury in Rats. In: Stem Cells Translational Medicine. 2019 ; Vol. 8, No. 9. pp. 959-970.
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