Cell Fusion in Functional Regeneration of the Mouse Retina

Not so long ago a reader asked me about cell fusion in relation to repairing age-damaged cells, and I noted that while some work on cell fusion is taking place it seems far less researched as a basis for regenerative therapies than, say, straightforward stem cell transplants. I certainly don't see much on this topic in the course of my browsing.

Still, fusion of transplanted stem cells with local cells shows up in the recent work linked below, in which researchers demonstrate partial functional regeneration of damaged retinal tissue in mice - which is a pretty big deal as an outcome, and I can't imagine that the authors will have any trouble finding additional funds to move ahead with their work. It seems that the fusion process can effectively be used as a form of cell reprogramming, and fused cells go on to take useful actions that repair surrounding tissues to a degree that would otherwise not occur. Press materials on this research are doing the rounds:

A Step Forward in Neuronal Regeneration

Researchers from the Centre for Genomic Regulation (CRG) in Barcelona have managed to regenerate the retina thanks to neuronal reprogramming. There are currently several lines of research that explore the possibility of tissue regeneration through cell reprogramming. One of the mechanisms being studied is reprogramming through cell fusion. [Researchers] have used the cell fusion mechanism to reprogramme the neurones in the retina. This mechanism consists of introducing bone marrow stem cells into the damaged retina. The new undifferentiated cells fuse with the retinal neurones and these acquire the ability to regenerate the tissue.

Here is the open access paper for those who want to dig in deeper to the mechanisms involved and discussion of the work by the researchers:

Wnt/β-Catenin Signaling Triggers Neuron Reprogramming and Regeneration in the Mouse Retina

Cell-fusion-mediated somatic-cell reprogramming can be induced in culture; however, whether this process occurs in mammalian tissues remains enigmatic. Here, we show that upon activation of Wnt/β-catenin signaling, mouse retinal neurons can be transiently reprogrammed in vivo back to a precursor stage. This occurs after their spontaneous fusion with transplanted hematopoietic stem and progenitor cells (HSPCs). Moreover, we demonstrate that retinal damage is essential for cell-hybrid formation in vivo.

Newly formed hybrids can proliferate, commit to differentiation toward a neuroectodermal lineage, and finally develop into terminally differentiated neurons. This results in partial regeneration of the damaged retinal tissue, with functional rescue. We show that upon [induced] retinal damage, transplanted stem and progenitor cells (SPCs), such as mouse hematopoietic stem and progenitor cells (mHSPCs), human (h)HSPCs, retinal (R)SPCs, and embryonic stem cells, can fuse with retinal neurons in vivo with high efficiency. Importantly, we show that the fate of these hybrids is to embark upon apoptosis unless Wnt/β-catenin signaling is activated in the transplanted cells.

Indeed, the activation of the Wnt pathway induces reprogramming of retinal neurons back to precursor or embryonic stages after HSPC or ESC fusion, respectively. HSPC-derived reprogrammed hybrids can proliferate and in turn differentiate into ganglion and amacrine neurons, thereby contributing to retinal regeneration. Remarkably, multielectrode recordings of retinal explants showed functional rescue of ganglion neurons to light response in the regenerated retinas.

The next stage in this research is to improve the quality of the result, and demonstrate that the signs of restored function observed here translate into restored sight. We shall see how long that takes to arrive.

Comments

My mom has a detatched retina (unsuccessfully or at least mostly unsuccessfully) operated on 10-15 years ago. I am wondering if there is any hope or regenerative therapies to fix this?

Posted by: Bob at July 14th, 2013 5:45 PM

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