Transplantation of a multipotent cell population from human adipose tissue induces dystrophin expression in the immunocompetent mdx mouse.

Here, we report the isolation of a human multipotent adipose-derived stem (hMADS) cell population from adipose tissue of young donors. hMADS cells display normal karyotype; have active telomerase; proliferate >200 population doublings; and differentiate into adipocytes, osteoblasts, and myoblasts. Flow cytometry analysis indicates that hMADS cells are CD44+, CD49b+, CD105+, CD90+, CD13+, Stro-1(-), CD34-, CD15-, CD117-, Flk-1(-), gly-A(-), CD133-, HLA-DR(-), and HLA-I(low). Transplantation of hMADS cells into the mdx mouse, an animal model of Duchenne muscular dystrophy, results in substantial expression of human dystrophin in the injected tibialis anterior and the adjacent gastrocnemius muscle. Long-term engraftment of hMADS cells takes place in nonimmunocompromised animals. Based on the small amounts of an easily available tissue source, their strong capacity for expansion ex vivo, their multipotent differentiation, and their immune-privileged behavior, our results suggest that hMADS cells will be an important tool for muscle cell-mediated therapy.

Segmental duplications in euchromatic regions of human chromosome 5: a source of evolutionary instability and transcriptional innovation.

Recent analyses of the structure of pericentromeric and subtelomeric regions have revealed that these particular regions of human chromosomes are often composed of blocks of duplicated genomic segments that have been associated with rapid evolutionary turnover among the genomes of closely related primates. In the present study, we show that euchromatic regions of human chromosome 5-5p14, 5p13, 5q13, 5q15-5q21-also display such an accumulation of segmental duplications. The structure, organization and evolution of those primate-specific sequences were studied in detail by combining in silico and comparative FISH analyses on human, chimpanzee, gorilla, orangutang, macaca, and capuchin chromosomes. Our results lend support to a two-step model of transposition duplication in the euchromatic regions, with a founder insertional event at the time of divergence between Platyrrhini and Catarrhini (25-35 million years ago) and an apparent burst of inter- and intrachromosomal duplications in the Hominidae lineage. Furthermore, phylogenetic analysis suggests that the chronology and, likely, molecular mechanisms, differ regarding the region of primary insertion-euchromatic versus pericentromeric regions. Lastly, we show that as their counterparts located near the heterochromatic region, the euchromatic segmental duplications have consistently reshaped their region of insertion during primate evolution, creating putative mosaic genes, and they are obvious candidates for causing ectopic rearrangements that have contributed to evolutionary/genomic instability.

Fusion of COL1A1 exon 29 with PDGFB exon 2 in a der(22)t(17;22) in a pediatric giant cell fibroblastoma with a pigmented Bednar tumor component. Evidence for age-related chromosomal pattern in dermatofibrosarcoma protuberans and related tumors.

In contrast with classic dermatofibrosarcoma protuberans (DP), genetic information about the juvenile or pigmented variant forms of DP, so-called giant cell fibroblastoma (GCF) and Bednar tumor (BT), is limited. In the sole karyotyped case of BT a supernumerary ring containing chromosomes 17 and 22 sequences, similar to DP rings, was reported, whereas in three GCF cases, t(17;22) or der(22)t(17;22) with COL1A1-PDGFB fusion involving exons 11, 40, and 47, respectively, have been described. Here, we report the first cytogenetic and molecular analysis of a tumor from a 5-year-old child that contained both GCF and BT components. The karyotype and molecular analyses confirmed the common histogenetic origin between DP, GCF, and BT in showing the presence of a der(22)t(17;22) fusing the COL1A1 exon 29 to PDGFB exon 2. Because COL1A1 exon 29 has been involved previously in gene fusion with PDGFB exon 2 in several cases of adult or infantile DP presenting either t(17;22) or ring chromosomes, our results support the concept that DP, GCF, and BT are morphologic variants of a same entity, rather than distinct tumors. Of interest, our findings give prominence to the relation between patient age and the chromosomal rearrangement pattern in DP and related tumors. Whereas only a few adult DP cases presented with translocations, all the infantile cases, either DP, GCF, or mixed BT-GCF, as shown here, contained translocation derivatives but not ring chromosomes. All the ring chromosomes were observed in adult cases. With respect to cytogenetic studies, DP, GCF, and BT appear to be a unique model for age-related chromosomal rearrangement progression.