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Scientists inch closer to regrowing spinal tissue

Feb. 28, 2007
Courtesy Forsyth Institute
and World Science staff

Sci­en­tists have in­duced a frog tad­pole to re­grow a lost tail at a stage in de­vel­op­ment when it’s nor­mal­ly im­pos­si­ble. The find­ings could rep­re­sent a step to­ward re­gen­er­at­ing dam­aged hu­man spi­nal cord tis­sue, they say.

Courtesy NJPC
Us­ing sev­er­al meth­ods in­clud­ing a kind of gene ther­a­py, the re­search­ers said they al­tered the elec­tri­cal prop­er­ties of cells to in­duce re­gen­er­a­tion. 

The work gave sci­en­tists a glimpse of the source of nat­u­ral elec­tric fields cru­cial for re­gen­er­a­tion, they said, and re­vealed how these orig­i­nate. 

The find­ings al­so pro­vided a first de­tailed ac­count of elec­tri­cal, mo­lec­u­lar-genetic, and cell-biological events be­hind re­gen­er­a­tion of the tail, they added. The struc­ture in­cludes skin, mus­cle, blood ves­sels and spi­nal cord. 

Al­though the tad­pole can some­times re-grow its tail, there are times dur­ing de­vel­op­ment that it can­not, much as hu­man chil­dren lose an abil­i­ty to re­gen­er­ate finger­tips af­ter about sev­en years of age. 

The re­search­ers, with the For­syth In­sti­tute in Bos­ton, in­tro­duced in­to tad­pole cells the yeast ver­sion of a gene for a cel­lu­lar struc­ture called a pro­ton pump. 

This is a com­plex of mo­le­cules that moves atom­ic com­po­nents called pro­tons across a cell mem­brane, an ac­tiv­i­ty that in turn drives var­i­ous key cel­lu­lar pro­cesses. The pump changes a cell’s elec­t­ri­cal prop­er­ties be­cause the pro­ton it­self car­ries elec­t­ric charge. 

Stim­u­lat­ing the pump’s ac­tiv­i­ty through ap­plied elec­tric fields trig­gered the re­gen­er­a­tion of the tail, the re­search­ers said. The find­ings are to ap­pear in the April is­sue of the re­search jour­nal De­vel­op­ment. 

The in­sti­tute’s Dany Ad­ams, first au­thor of the pa­per, said ap­plied elec­tric fields have long been known to en­hance re­gen­er­a­tion in am­phib­ians, and in fact have led to clin­i­cal tri­als in hu­mans. “How­ever, the mo­lec­u­lar sources of rel­e­vant cur­rents and the mech­a­nisms un­der­ly­ing their con­trol have re­mained poor­ly un­der­stood,” he said. 

“To tru­ly make strides in re­gen­er­a­tive med­i­cine, we need to un­der­stand the in­nate com­po­nents that un­der­lie bioe­lec­tri­cal events dur­ing nor­mal de­vel­op­ment and re­gen­er­a­tion,” he added. “We have found at least one crit­i­cal com­po­nent.”

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Scientists have induced a frog tadpole to re-grow its tail at a stage in development when it’s normally impossible. The findings could represent a step toward regenerating damaged human spinal cord tissue, they say. Using several methods including a kind of gene therapy, the scientists altered the electrical properties of cells to induce regeneration. This discovery may provide clues about how bioelectricity can be used to help humans regenerate. This study gave scientists a glimpse of the source of natural electric fields crucial for regeneration, they said, and revealed how these originate. The findings also provided a first detailed account of electrical, molecular-genetic, and cell-biological events underlying the regeneration of the tail, which includes skin, muscle, blood vessels and spinal cord. Although the tadpole can sometimes re-grow its tail, there are specific times during its development that regeneration does not take place, much as human children lose an ability to regenerate finger-tips at about seven years of age. The researchers, with the Forsyth Institute in Boston, introduced into tadpole cells with the yeast version of a gene for a cellular structure called a proton pump. This is a complex of molecules that moves atomic components called protons across a cell membrane, an activity that in turn drives various key cellular processes. Stimulating the pump’s activity through applied electric fields triggered the regeneration of the frog’s tail during the normally quiescent time, they said. The findings are to appear in the April issue of the research journal Development and will appear online on February 28, 2007. The institute’s Dany Adams, first author of the paper, said applied electric fields have long been known to enhance regeneration in amphibia, and in fact have led to clinical trials in human patients. “However, the molecular sources of relevant currents and the mechanisms underlying their control have remained poorly understood,” he said. “To truly make strides in regenerative medicine, we need to understand the innate components that underlie bioelectrical events during normal development and regeneration. Our ability to stop regeneration by blocking a particular H+ pump and to induce regeneration when it is normally absent, means we have found at least one critical component.”