Chromosome transplantation as a novel approach for correcting complex genomic disorders.
Genomic disorders resulting from large rearrangements of the genome remain an important unsolved issue in gene therapy. Chromosome transplantation, defined as the perfect replacement of an endogenous chromosome with a homologous one, has the potential of curing this kind of disorders. Here we report the first successful case of chromosome transplantation by replacement of an endogenous X chromosome carrying a mutation in the Hprt genewith a normal one in mouse embryonic stem cells (ESCs), correcting the genetic defect. The defect was also corrected by replacing the Y chromosome with an X chromosome. Chromosome transplanted clones maintained in vitro and in vivo features of stemness and contributed to chimera formation. Genome integrity was confirmed by cytogenetic and molecular genome analysis. The approach here proposed, with some modifications, might be used to cure various disorders due to other X chromosome aberrations in induced pluripotent stem (iPS) cells derived from affected patients.
Milan Unit, Istituto di Ricerca Genetica e Biomedica, CNR, Milan, Italy.|Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
Marianna
M
Paulis
Milan Unit, Istituto di Ricerca Genetica e Biomedica, CNR, Milan, Italy.|Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
Alessandra
A
Castelli
Milan Unit, Istituto di Ricerca Genetica e Biomedica, CNR, Milan, Italy.|Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
Lucia
L
Susani
Humanitas Clinical and Research Center, Rozzano, Milan, Italy.|Centro Ricerche Biotecnologiche, Università Cattolica del Sacro Cuore, Cremona, Italy.
Michela
M
Lizier
Avantea, Cremona, Italy.
Irina
I
Lagutina
Milan Unit, Istituto di Ricerca Genetica e Biomedica, CNR, Milan, Italy.|Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
Maria Luisa
ML
Focarelli
Mouse and Animal Pathology Laboratory, Fondazione Filarete, Milan, Italy.
Camilla
C
Recordati
CRS4 Bioinformatics Laboratory, Parco Scientifico e Tecnologico POLARIS, Pula, Cagliari, Italy.
Paolo
P
Uva
Milan Unit, Istituto di Ricerca Genetica e Biomedica, CNR, Milan, Italy.|Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
Francesca
F
Faggioli
Milan Unit, Istituto di Ricerca Genetica e Biomedica, CNR, Milan, Italy.|Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
Tui
T
Neri
Mouse and Animal Pathology Laboratory, Fondazione Filarete, Milan, Italy.|Department of Veterinary Sciences and Public Health, University of Milan, Milan, Italy.
Eugenio
E
Scanziani
Avantea, Cremona, Italy.|Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.
Cesare
C
Galli
Centro Ricerche Biotecnologiche, Università Cattolica del Sacro Cuore, Cremona, Italy.
Franco
F
Lucchini
Milan Unit, Istituto di Ricerca Genetica e Biomedica, CNR, Milan, Italy.|Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
Anna
A
Villa
Milan Unit, Istituto di Ricerca Genetica e Biomedica, CNR, Milan, Italy.|Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
Paolo
P
Vezzoni
D000818:Animals; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology; D030342:Genetic Diseases, Inborn / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D009154:Mutation; D014960:X Chromosome
D007041:Hypoxanthine Phosphoribosyltransferase
cell therapy; chromosome transplantation; embryonic stem cells; genomic disorders; microcell fusion