Intraperitoneal administration of adipose tissue-derived stem cells for the rescue of retinal degeneration in a mouse model via indigenous CNTF up-regulation by IL-6

J Tissue Eng Regen Med. 2018 Mar;12(3):e1370-e1382. doi: 10.1002/term.2522. Epub 2017 Nov 21.

Abstract

As the world's population begins to age, retinal degeneration is an increasing problem, and various treatment modalities are being developed. However, there have been no therapies for degenerative retinal conditions that are not characterized by neovascularization. We investigated whether transplantation of mouse adipose tissue-derived stem cells (mADSC) into the intraperitoneal space has a rescue effect on NaIO3 -induced retinal degeneration in mice. In this study, mADSC transplantation recovered visual function and preserved the retinal outer layer structure compared to the control group without any integration of mADSC into the retina. Moreover, endogenous ciliary neurotrophic factor (CNTF) was elevated in the retinas of mADSC-treated mice. We found that lipopolysaccharide (LPS) or LPS-stimulated monocyte supernatant induced the secretion of granulocyte colony stimulating factor (GCSF), CD54, CXCL10, interleukin-6 (IL-6), and CCL5 from the mADSC by cytokine array. Network inference was conducted to investigate signaling networks related to CNTF regulation. Based on bioinformatics data, the expression of IL-6 was related to the expression of CNTF. Additionally, intravitreal injection of IL-6 in rats produced up-regulation of endogenous CNTF in the retina. mADSC had a rescue effect on retinal degeneration through the up-regulation of endogenous CNTF by IL-6. Thus, transplantation of mADSC could be a potential treatment option for retinal degeneration.

Keywords: Interleukin-6; adipose tissue-derived stem cells; ciliary neurotrophic factor (CNTF); mesenchymal stem cells; retinal degeneration; transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Animals
  • Cells, Cultured
  • Ciliary Neurotrophic Factor / metabolism*
  • Disease Models, Animal
  • Injections, Intraperitoneal
  • Interleukin-6 / blood
  • Interleukin-6 / metabolism*
  • Intravitreal Injections
  • Iodates
  • Lipopolysaccharides / pharmacology
  • Mice, Inbred C57BL
  • Protective Agents / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Retinal Degeneration / blood
  • Retinal Degeneration / genetics
  • Retinal Degeneration / pathology
  • Retinal Degeneration / therapy*
  • Retinal Pigment Epithelium / pathology
  • Stem Cell Transplantation*
  • Stem Cells / cytology*
  • Up-Regulation*

Substances

  • Ciliary Neurotrophic Factor
  • Interleukin-6
  • Iodates
  • Lipopolysaccharides
  • Protective Agents
  • RNA, Messenger
  • sodium iodate