FV 969. Transplantation Surgery Used Autologous Transgenic Keratinocyte Cultures Which Regenerated an Entire, Fully Functional Epidermis

Background: Generalized junctional epidermolysis bullosa is a hereditary, often lethal genetic disease characterized by the development of blisters, skin erosion, or chronic wounds in response to minor trauma. Motor impairment or motor developmental delay accompanies the clinical manifestation of this noncurable disease. About 40% of all juvenile patients suffering from JEB die before adolescence.¹ In 2015, a team of researchers of the Ruhr-University Bochum and the University of Modena, however, succeeded in restoring the epidermis in a 7-year-old boy who suffered from complete and life-threatening epidermal loss of ∼80% of total body surface areas. Transplantation surgery used autologous transgenic keratinocyte cultures which regenerated an entire, fully functional epidermis. To date, this epidermis remains resistant to mechanical stress. A postoperative quantitative sensory testing showed normative perception thresholds, indicating preserved peripheral sensory processing by intact functioning of the C-, α-, and Aβ fibers. It remains to be clarified however, if all aspects of somatosensory processing, in particular those mediated by central processes, are “fully functional.” This issue is of particular interest, as it addresses the question whether an epidermis regenerated by genetically modified stem cells reinstates full afferent neuron, cell, and receptor function, that is, functioning beyond the relay of peripheral signals to an intact processing and integration of tactile and proprioceptive stimuli into a neuronal body representation in the primary somatosensory cortex. This aspect of the neuronal body representation mediates perception and location of stimuli associated with the sensation of touch, itch, or pain on the body (somatoperception) and is crucial for motor planning, coordinated movement in space and bodily self-perception.²

It is therefore of crucial interest to clarify if an epidermis regenerated by genetically modified stem cells interconnects to the central somatosensory processes that mediate the neuronal composition of body representation underlying (bodily) self-perception.

Aim: To clarify the functionality of tactile and proprioceptive processing and integration of regenerated skin grafts into the neuronal body representation within (S1) and to assess the neuronal interconnection and interplay between peripheral and central sensory processing in the renewed epidermis areas.

Question: Are the psychophysical correlates of fully functional somatosensory processing and multisensory integration, namely, the phenomenon of tactile anisotropy (direction-dependent perception of tactile distances) and illusory ownership of a rubber hand illusion observable?

Methods: Well-established psychophysiological paradigms will investigate processing of tactile and proprioceptive stimuli (paradigm: tactile distance judgement³) and their integration (paradigm: rubber hand illusion⁴) into a neuronal body representation in S1. Neurocognitive status, socioemotional, and motor development will be tested using standardized psychometrical test batteries.

Results: Test results show the functionality of central somatosensory processes, intactness of a neuronal body representation, and socioemotional and motor developmental status of the currently 9-year-old boy.

Conclusion: Observed functionality of the regenerated skin indicates a fully preserved and intact neuronal body representation. These findings imply that the skin evolving from genetically modified stem cells retains all aspects of somatosensory processing and is integrated wholly into a neuronal body representation in the primary somatosensory cortex.

References

1. Hirsch T, Rothoeft T, Teig N, et al. Regeneration of the entire human epidermis using transgenic stem cells. Nature 2017;551(7680):327–332

2. Reinersmann A, Lücke T. Zum Zusammenhang zwischen Körperschema und sozio-emotionalen Verhalten bei umschriebenen Entwicklungsstörungen der Wahrnehmung und Motorik. Fortschr Neurol Psychiatr 2018;86(4):233–241

3. Longo MR, Haggard P. Weber’s illusion and body shape: anisotropy of tactile size perception on the hand. J Exp Psychol Hum Percept Perform 2011;37(3):720–726

4. Reinersmann A, Landwehrt J, Krumova EK, et al. The rubber hand illusion in complex regional pain syndrome: preserved ability to integrate a rubber hand indicates intact multisensory integration. Pain 2013;154(9):1519–1527

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