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Two is better than one for MSC Treatment of Retinal Degeneration

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Review of “Multimodal Delivery of Isogenic Mesenchymal Stem Cells Yields Synergistic Protection from Retinal Degeneration and Vision Loss” from Stem Cells Translational Medicine by Stuart P. Atkinson

The application of mesenchymal stem cells (MSCs) represents an exciting therapeutic option for a multitude of diseases and disorders, including the loss of vision associated with retinal degeneration. Researchers from the group of Shaomei Wang (Cedars-Sinai Medical Center, Los Angeles, USA) recently demonstrated that two different rat MSC transplantation modes provided distinct pro-regenerative effects in a rat retinal degeneration model. Their studies demonstrated that subretinally injected MSCs (MSCSRI) promoted site-specific retinal protection and vision rescue [1, 2] while intravenously injected MSCs (MSCIV) provided general retinal support [3]. 

In a new Stem Cells Translational Medicine study, the Wang team has now assessed the combination of these two MSC transplantation modes with the hope of uncovering a synergistic effect [4]. Will this study conclude that two is better than one for MSC-based retinal degeneration therapy?

Encouragingly, initial analyses suggested that MSCIV treatment synergized with MSCSRI-treatment, yielding the highest visual acuity, retinal sensitivity to light (See Figure), and photoreceptor rescue area in the retina as compared to single treatments. Pre-treatment with the CXCR4 agonist (CXCL12) aimed to enhance MSCIV chemotaxis to further boost regenerative capacity and the application of this strategy led to enhanced photoreceptor and vision rescue. However, these improvements did not correlate with higher levels of MSC retinal recruitment; but instead, further work suggested that trophic support and systemic immunomodulation, as evidenced by reduced levels of platelets and lymphocytes, represented the most important contributions of MSCs.

The synergistic therapeutic response observed in this study suggests that, for MSC treatment of retinal degeneration, two is better than one! Additionally, the author’s findings advocate the use of MSCIV as a supplement to other cell-based therapies for progressive degenerative diseases of the retina and, perhaps, other sites of injury or disease. Further studies will aim to characterize the exact mechanisms at play behind this synergistic treatment and move this strategy closer to human trials. 

References

  1. Lund RD, Wang S, Lu B, et al. Cells isolated from umbilical cord tissue rescue photoreceptors and visual functions in a rodent model of retinal disease. Stem Cells 2007;25:602-611.
  2. Lu B, Wang S, Girman S, et al. Human adult bone marrow-derived somatic cells rescue vision in a rodent model of retinal degeneration. Exp Eye Res 2010;91:449-455.
  3. Wang S, Lu B, Girman S, et al. Non-invasive stem cell therapy in a rat model for retinal degeneration and vascular pathology. PLoS One 2010;5:e9200.
  4. Bakondi B, Girman S, Lu B, et al. Multimodal Delivery of Isogenic Mesenchymal Stem Cells Yields Synergistic Protection from Retinal Degeneration and Vision Loss. STEM CELLS Translational Medicine 2017;6:444-457.