Ocular Therapeutics Using Stem Cell Microvesicles

Tech ID: 29794 / UC Case 2012-189-0

Summary

Researchers in the UCLA Department of Ophthalmology have invented a method of using human embryonic stem cell microvesicles (hESMVs) to induce the regenerative capacity of several tissues, in particular, the ability to induce reconstruction of diseased retinas.

Background

There are currently over 180 million people worldwide suffering from blindness or some form of visual disability, and the demand for new retinal disease treatments is expected to rise quickly. Stem cells are a promising technology in this field; however, this method poses a risk of incorrect differentiation and malignant cell transformation. Human embryonic stem cell microvesicles (hESMVs) are microvesicles released into the extracellular environment by human embryonic stem cells that induce the regenerative capacity of several tissues. hESMVs have been shown to induce the endogenous regenerative capacity of blood, liver, kidney, and lung tissues, and to produce similar biological effects than the ESCs from which they are derived. Additionally, ESMVs from cultured mouse ESCs have demonstrated an ability to transfer to RNA and proteins from cell to cell. hESMVs may therefore stimulate regeneration by inducing endogenous Müller cells to repopulate and repair damaged retina, and their use may avoid the possible long-term maldifferentiation of engrafted intact hESCs and eliminate the risk of their malignant transformation.

Innovation

A research team lead by Dr. Debora B. Farber in the UCLA Department of Ophthalmology has invented a method of using hESMVs to induce the reconstruction of diseased retinas. In vitro testing is underway with preliminary results outlined below. Integrating hESMVs into stem cell-based ocular therapeutics use can avoid the possible maldifferentiation and malignant transformation of engrafted hESCs.

Applications

Treatment of retinal degenerative diseases:

  • Glaucoma 
  • Age-related macular degeneration (AMD) 
  • Diabetic retinopathy

 

Advantages

  • Higher gain (increased detection sensitivity) 
  • Double sampling (reduced noise)

State Of Development

  • Published work has demonstrated the ability of mouse ESMVs to transfer to fibroblasts stem cell mRNA, miRNA, and protein, suggesting that stem cells alter gene expression in target cells by ESMV-mediated transfers.  
  • It has also been shown that cultured Müller cells exposed to mESMVs up-regulate pluripotency and early retinal genes, genes involved in retinal protection and regeneration, and extracellular matrix modifying genes known to create permissive environment for tissue remodeling, whereas they down-regulate genes promoting differentiation (DNMT3a and GATA4).  
  • Most importantly, a very promising improvement has been demonstrated in both the a and b waves of mouse electroretinography as well as immunohistochemical evidence of cell proliferation after intraocular injection of mouse ESMVs into NMDA (N-methyl-D-aspartate)-damaged retina.

Patent Status

Country Type Number Dated Case
United States Of America Published Application 20150079047 03/19/2015 2012-189
 

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Inventors

  • Farber, Debora B.

Other Information

Keywords

Embryonic stem cell microvesicles (ESMVs), ophthalmic diseases, retinal degenerative diseases, regenerative medicine, cell signaling, ERG

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