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  4. Single-cell transcriptome analysis of xenotransplanted human retinal organoids defines two migratory cell populations of nonretinal origin

Single-cell transcriptome analysis of xenotransplanted human retinal organoids defines two migratory cell populations of nonretinal origin

Stem Cell Reports, 2023 · DOI: https://doi.org/10.1016/j.stemcr.2023.04.004 · Published: May 9, 2023

Regenerative MedicineNeurology

Simple Explanation

This study investigates how the recipient retina influences transplanted human retinal organoid cells. Human retinal organoid-derived cells were transplanted into photoreceptor-deficient mice to observe cell behavior. Unexpectedly, some human cells migrated into all layers of the recipient retina and traveled long distances. These migratory cells were identified as astrocytes and brain/spinal cord-like neural precursors. Retinal progenitor-derived rods and cones remained in the subretinal space and matured faster than in cultured controls. This suggests the recipient microenvironment supports photoreceptor maturation and survival of non-retinal migratory cells.

Study Duration
4.5 months
Participants
Photoreceptor-deficient mice (C3H/HeJ-Pde6bRd1/Rd1 and NOD.Cg-Prkdcscid/J double mutant mice)
Evidence Level
Not specified

Key Findings

  • 1
    Human cells transplanted into mice retinas migrated into all retinal layers, identified as astrocytes and brain/spinal cord-like neural precursors.
  • 2
    Transplanted photoreceptors matured more rapidly in the subretinal space of recipient mice compared to cultured organoids.
  • 3
    The recipient microenvironment promotes the survival and maturation of exogenous photoreceptor cells.

Research Summary

The study investigates the behavior of transplanted human retinal organoid cells in photoreceptor-deficient mice. It examines how the recipient retina affects the survival, maturation, and proliferation of these transplanted cells. Unexpectedly, human cells were found to migrate into all recipient retinal layers, identified as astrocytes and brain/spinal cord-like neural precursors. These cells were rare or absent in cultured organoids. The study suggests that the recipient microenvironment promotes the maturation of transplanted photoreceptors and induces the survival of migratory cell populations not normally derived from retinal progenitors.

Practical Implications

Cell-based therapies for retinal diseases

Findings have implications for cell-based treatments of retinal diseases, particularly in understanding how the recipient microenvironment influences transplanted cells.

Regulating donor cell migration

Studying donor cell migration may help develop strategies to regulate their spatial targeting for therapeutic purposes.

Optimizing retinal organoid transplantation

Understanding the differences between transplanted and cultured organoids can help optimize transplantation protocols.

Study Limitations

  • 1
    Temporal resolution to determine if transplantation induces trans-differentiation.
  • 2
    The cues in the recipient microenvironment that promote cell migration and photoreceptor maturation are not known.
  • 3
    Whether migratory donor cells negatively affect recipient retinal function is unknown.

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