Human umbilical tissue-derived cells rescue retinal pigment epithelium dysfunction in retinal degeneration

Jing Cao, Christopher Murat, Weijun An, Xiang Yao, John Lee, Sandra Santulli-Marotto, Ian R. Harris, George Inana

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Retinal pigment epithelium (RPE) cells perform many functions crucial for retinal preservation and vision. RPE cell dysfunction results in various retinal degenerative diseases, such as retinitis pigmentosa and age-related macular degeneration (AMD). Currently, there are no effective treatments for retinal degeneration except for a small percentage of individuals with exudative AMD. Cell therapies targeting RPE cells are being developed in the clinic for the treatment of retinal degeneration. Subretinal injection of human umbilical tissue-derived cells (hUTC) in the Royal College of Surgeons (RCS) rat model of retinal degeneration was shown to preserve photoreceptors and visual function. However, the precise mechanism remains unclear. Here, we demonstrate that hUTC rescue phagocytic dysfunction in RCS RPE cells in vitro. hUTC secrete receptor tyrosine kinase (RTK) ligands brain-derived neurotrophic factor (BDNF), hepatocyte growth factor (HGF), and glial cell-derived neurotrophic factor (GDNF), as well as opsonizing bridge molecules milk-fat-globule-epidermal growth factor 8 (MFG-E8), growth arrest-specific 6 (Gas6), thrombospondin (TSP)-1, and TSP-2. The effect of hUTC on phagocytosis rescue in vitro is mimicked by recombinant human proteins of these factors and is abolished by siRNA-targeted gene silencing in hUTC. The bridge molecules secreted from hUTC bind to the photoreceptor outer segments and facilitate their ingestion by the RPE. This study elucidates novel cellular mechanisms for the repair of RPE function in retinal degeneration through RTK ligands and bridge molecules, and demonstrates the potential of using hUTC for the treatment of retinal degenerative diseases.

Original languageEnglish (US)
Pages (from-to)367-379
Number of pages13
JournalStem Cells
Volume34
Issue number2
DOIs
StatePublished - Feb 1 2016

Fingerprint

Umbilicus
Retinal Degeneration
Retinal Pigment Epithelium
Retinal Diseases
Macular Degeneration
Receptor Protein-Tyrosine Kinases
Ligands
Thrombospondin 1
Cytophagocytosis
Retinitis Pigmentosa
Hepatocyte Growth Factor
Brain-Derived Neurotrophic Factor
Nerve Growth Factors
Gene Silencing
Phagocytes
Cell- and Tissue-Based Therapy
Recombinant Proteins
Epidermal Growth Factor
Neuroglia
Small Interfering RNA

Keywords

  • Bridge molecules
  • Cell therapy
  • Phagocytosis
  • Receptor tyrosine kinase
  • Retinal degeneration
  • Retinal pigment epithelium

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

Cite this

Human umbilical tissue-derived cells rescue retinal pigment epithelium dysfunction in retinal degeneration. / Cao, Jing; Murat, Christopher; An, Weijun; Yao, Xiang; Lee, John; Santulli-Marotto, Sandra; Harris, Ian R.; Inana, George.

In: Stem Cells, Vol. 34, No. 2, 01.02.2016, p. 367-379.

Research output: Contribution to journalArticle

Cao, J, Murat, C, An, W, Yao, X, Lee, J, Santulli-Marotto, S, Harris, IR & Inana, G 2016, 'Human umbilical tissue-derived cells rescue retinal pigment epithelium dysfunction in retinal degeneration', Stem Cells, vol. 34, no. 2, pp. 367-379. https://doi.org/10.1002/stem.2239
Cao, Jing ; Murat, Christopher ; An, Weijun ; Yao, Xiang ; Lee, John ; Santulli-Marotto, Sandra ; Harris, Ian R. ; Inana, George. / Human umbilical tissue-derived cells rescue retinal pigment epithelium dysfunction in retinal degeneration. In: Stem Cells. 2016 ; Vol. 34, No. 2. pp. 367-379.
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