A new study con­duct­ed at the Uni­ver­si­ty of Copen­hagen chal­lenges tra­di­tion­al knowl­edge of stem cell devel­op­ment. The study reveals that the des­tiny of intesti­nal cells is not pre­de­ter­mined, but instead deter­mined by the cells’ sur­round­ings. The find­ings may make it eas­i­er to manip­u­late stem cells for stem cell ther­a­py. Results have just been pub­lished in Nature.

All cells in the fetal gut have the poten­tial to devel­op into stem cells, a new study con­duct­ed at the Fac­ul­ty of Health and Med­ical Sci­ences at the Uni­ver­si­ty of Copen­hagen con­cludes. The researchers behind the study have dis­cov­ered that the devel­op­ment of imma­ture intesti­nal cells — con­trary to pre­vi­ous assump­tions — is not pre­de­ter­mined, but affect­ed by the cells’ imme­di­ate sur­round­ings in the intestines. This dis­cov­ery may ease the path to effec­tive stem cell ther­a­py, says Asso­ciate Pro­fes­sor Kim Jensen from the Biotech Research & Inno­va­tion Cen­tre (BRIC) and the Novo Nordisk Foun­da­tion Cen­ter for Stem Cell Biol­o­gy (DanStem).

“We used to believe that a cel­l’s poten­tial for becom­ing a stem cell was pre­de­ter­mined, but our new results show that all imma­ture cells have the same prob­a­bil­i­ty for becom­ing stem cells in the ful­ly devel­oped organ. In prin­ci­ple, it is sim­ply a mat­ter of being in the right place at the right time. Here sig­nals from the cells’ sur­round­ings deter­mine their fate. If we are able to iden­ti­fy the sig­nals that are nec­es­sary for the imma­ture cell to devel­op into a stem cell, it will be eas­i­er for us to manip­u­late cells in the want­ed direc­tion.”

Through­out life the organs in the body are main­tained by stem cells, which are also able to repair minor tis­sue dam­age. A bet­ter under­stand­ing of the fac­tors that deter­mine whether or not an imma­ture cell devel­ops into a stem cell may there­fore be use­ful in the devel­op­ment of stem cells for ther­a­py and trans­plan­ta­tion.

‘We have gained greater insight into the mech­a­nisms through which cells in the imma­ture intestines devel­op into stem cells. Hope­ful­ly we are able to use this knowl­edge to improve treat­ment of non-heal­ing wounds, e.g. in the intestines. So far, though, all we can say for sure is that cells in the gas­troin­testi­nal tract have these char­ac­ter­is­tics. How­ev­er, we do believe this is a gen­er­al phe­nom­e­non in fetal organ devel­op­ment’.

Lumi­nes­cent Cells and Math­e­mat­i­cal Col­lab­o­ra­tion

The sur­pris­ing find­ings are the result of a search for under­stand­ing of what con­trols the des­tiny of intesti­nal stem cells. Post­doc Jor­di Guiu devel­oped a method for mon­i­tor­ing the devel­op­ment of the indi­vid­ual intesti­nal cells. By intro­duc­ing lumi­nes­cent pro­teins into the cells he could, using advanced microscopy, mon­i­tor the devel­op­ment of the indi­vid­ual cells.

After the ini­tial tests, the cells that researchers pre­vi­ous­ly believed to be fetal stem cells were only able to explain a frac­tion of the growth of the intestines dur­ing fetal devel­op­ment. There­fore, they estab­lished a col­lab­o­ra­tion with math­e­mat­i­cal experts at the Uni­ver­si­ty of Cam­bridge. And when they stud­ied the data more close­ly togeth­er, they arrived at the sur­pris­ing hypoth­e­sis that all intesti­nal cells may have the same chance of becom­ing stem cells. Sub­se­quent tests were able to prove the hypoth­e­sis.

“The next step is to deter­mine pre­cise­ly which sig­nals are nec­es­sary for imma­ture cells to devel­op into the kind of stem cells we need. This is one of our research focus­es,” says Kim Jensen.

Stem cells and stem cell ther­a­py facts

Through­out life stem cells help main­tain the organs in the body and repair dam­aged tis­sue. How­ev­er, the stem cells found in the body can only renew and repair minor tis­sue dam­age.

Using stem cell trans­plan­ta­tion and ther­a­py it is pos­si­ble to sup­ple­ment the body’s own cells with new, healthy stem cells that can help repair or replace dam­aged tis­sue.

The project was fund­ed by the Euro­pean Research Coun­cil, the Hori­zon 2020 research pro­gramme, the Lund­beck Foun­da­tion, the Novo Nordisk Foun­da­tion, the Carls­berg Foun­da­tion and the Marie Curie fel­low­ship pro­gramme.

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