Advances in bone marrow stem cell therapy for retinal dysfunction

Susanna S Park; Elad Moisseiev; Gerhard Bauer; Johnathon D Anderson; Maria B Grant; Azhar Zam; Robert J Zawadzki; John S Werner; Jan A Nolta

doi:10.1016/j.preteyeres.2016.10.002

Advances in bone marrow stem cell therapy for retinal dysfunction

Prog Retin Eye Res. 2017 Jan:56:148-165. doi: 10.1016/j.preteyeres.2016.10.002. Epub 2016 Oct 23.

Authors

Susanna S Park¹, Elad Moisseiev², Gerhard Bauer³, Johnathon D Anderson⁴, Maria B Grant⁵, Azhar Zam⁶, Robert J Zawadzki⁷, John S Werner⁸, Jan A Nolta⁹

Affiliations

¹ Department of Ophthalmology & Vision Science, University of California Davis, Sacramento, CA, 95817, USA. Electronic address: sscpark@ucdavis.edu.
² Department of Ophthalmology & Vision Science, University of California Davis, Sacramento, CA, 95817, USA. Electronic address: emoisseiev@ucdavis.edu.
³ Stem Cell Program, Institute for Regenerative Cures, University of California Davis, Sacramento, CA, 95817, USA. Electronic address: gbauer@ucdavis.edu.
⁴ Stem Cell Program, Institute for Regenerative Cures, University of California Davis, Sacramento, CA, 95817, USA. Electronic address: joanderson@ucdavis.edu.
⁵ Department of Ophthalmology, Glick Eye Institute, Indiana University, Indianapolis, IN, USA. Electronic address: mabgrant@iupui.edu.
⁶ UC Davis RISE Eye-Pod Small Animal Imaging Laboratory, Department of Cell Biology and Human Anatomy, University of California Davis, Davis, CA, USA. Electronic address: azam@ucdavis.edu.
⁷ Department of Ophthalmology & Vision Science, University of California Davis, Sacramento, CA, 95817, USA; UC Davis RISE Eye-Pod Small Animal Imaging Laboratory, Department of Cell Biology and Human Anatomy, University of California Davis, Davis, CA, USA. Electronic address: rjzawadzki@ucdavis.edu.
⁸ Department of Ophthalmology & Vision Science, University of California Davis, Sacramento, CA, 95817, USA. Electronic address: jswerner@ucdavis.edu.
⁹ Stem Cell Program, Institute for Regenerative Cures, University of California Davis, Sacramento, CA, 95817, USA. Electronic address: janolta@ucdavis.edu.

Abstract

The most common cause of untreatable vision loss is dysfunction of the retina. Conditions, such as age-related macular degeneration, diabetic retinopathy and glaucoma remain leading causes of untreatable blindness worldwide. Various stem cell approaches are being explored for treatment of retinal regeneration. The rationale for using bone marrow stem cells to treat retinal dysfunction is based on preclinical evidence showing that bone marrow stem cells can rescue degenerating and ischemic retina. These stem cells have primarily paracrine trophic effects although some cells can directly incorporate into damaged tissue. Since the paracrine trophic effects can have regenerative effects on multiple cells in the retina, the use of this cell therapy is not limited to a particular retinal condition. Autologous bone marrow-derived stem cells are being explored in early clinical trials as therapy for various retinal conditions. These bone marrow stem cells include mesenchymal stem cells, mononuclear cells and CD34⁺ cells. Autologous therapy requires no systemic immunosuppression or donor matching. Intravitreal delivery of CD34⁺ cells and mononuclear cells appears to be tolerated and is being explored since some of these cells can home into the damaged retina after intravitreal administration. The safety of intravitreal delivery of mesenchymal stem cells has not been well established. This review provides an update of the current evidence in support of the use of bone marrow stem cells as treatment for retinal dysfunction. The potential limitations and complications of using certain forms of bone marrow stem cells as therapy are discussed. Future directions of research include methods to optimize the therapeutic potential of these stem cells, non-cellular alternatives using extracellular vesicles, and in vivo high-resolution retinal imaging to detect cellular changes in the retina following cell therapy.

Keywords: Bone marrow; CD34; Hematopoietic; Mesenchymal; Retina; Stem cells.

Publication types

Review

MeSH terms

Animals
Bone Marrow Cells / classification*
Humans
Mesenchymal Stem Cells / cytology*
Retinal Diseases / surgery*
Stem Cell Transplantation / methods*

Abstract

Publication types

MeSH terms

Grants and funding