title: EphB2 isolates a human marrow stromal cell subpopulation with enhanced ability to contribute to the resident intestinal cellular pool.
abstract: To identify human bone marrow stromal cell (BMSC) subsets with enhanced ability to engraft/contribute to the resident intestinal cellular pool, we transplanted clonally derived BMSCs into fetal sheep. Analysis at 75 d post-transplantation showed 2 of the 6 clones engrafting the intestine at 4- to 5-fold higher levels (5.03±0.089 and 5.04±0.15%, respectively) than the other clones (P<0.01), correlating with the percentage of donor-derived Musashi-1(+) (12.01-14.17 vs. 1.2-3.8%; P<0.01) or leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5)(+) cells within the intestinal stem cell (ISC) region. Phenotypic and transcriptome analysis determined that the clones with enhanced intestinal contribution expressed high levels of Ephrin type B receptor 2 (EphB2). Intestinal explants demonstrated proliferation of the engrafted cells and ability to generate crypt-like structures in vitro still expressing EphB2. Additional transplants based on BMSC EphB2 expression demonstrated that, at 7 d post-transplant, the EphB2(high) BMSCs engrafted in the ISC region at levels of 2.1 ± 0.2%, while control EphB2(low) BMSCs engrafted at 0.3 ± 0.1% (P<0.01). Therefore we identified a marker for isolating and culturing an expandable subpopulation of BMSCs with enhanced intestinal homing and contribution to the ISC region.
authors: Department of Animal Biotechnology, University of Nevada, Reno, Nevada, USA.
authors: Evan
authors: E
authors: Colletti
authors: Deena
authors: D
authors: El Shabrawy
authors: Melisa
authors: M
authors: Soland
authors: Takashi
authors: T
authors: Yamagami
authors: Saloomeh
authors: S
authors: Mokhtari
authors: Craig
authors: C
authors: Osborne
authors: Karen
authors: K
authors: Schlauch
authors: Esmail D
authors: ED
authors: Zanjani
authors: Christopher D
authors: CD
authors: Porada
authors: Graça
authors: G
authors: Almeida-Porada
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019070:Cell Lineage; D005260:Female; D005333:Fetus; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D007421:Intestine, Small / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000145:classification* / Q000166:cytology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D036183:Receptor, EphB2 / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D012756:Sheep; D055153:Stem Cell Niche; D059467:Transcriptome; D014183:Transplantation, Heterologous
chemical_list: D015415:Biomarkers; C116884:LGR5 protein, human; C491297:MSI1 protein, human; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D043562:Receptors, G-Protein-Coupled; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D036183:Receptor, EphB2
keywords: Lgr5; Musashi-1; crypts of Lieberkühn; epithelial; niche; transcriptome; transplant