title: Human umbilical cord blood-borne fibroblasts contain marrow niche precursors that form a bone/marrow organoidin vivo.
abstract: Human umbilical cord blood (CB) has attracted much attention as a reservoir for functional hematopoietic stem and progenitor cells, and, recently, as a source of blood-borne fibroblasts (CB-BFs). Previously, we demonstrated that bone marrow stromal cell (BMSC) and CB-BF pellet cultures make cartilagein vitroFurthermore, uponin vivotransplantation, BMSC pellets remodelled into miniature bone/marrow organoids. Using thisin vivomodel, we asked whether CB-BF populations that express characteristics of the hematopoietic stem cell (HSC) niche contain precursors that reform the niche. CB ossicles were regularly observed upon transplantation. Compared with BM ossicles, CB ossicles showed a predominance of red marrow over yellow marrow, as demonstrated by histomorphological analyses and the number of hematopoietic cells isolated within ossicles. Marrow cavities from CB and BM ossicles included donor-derived CD146-expressing osteoprogenitors and host-derived mature hematopoietic cells, clonogenic lineage-committed progenitors and HSCs. Furthermore, human CD34+cells transplanted into ossicle-bearing mice engrafted and maintained human HSCs in the niche. Our data indicate that CB-BFs are able to recapitulate the conditions by which the bone marrow microenvironment is formed and establish complete HSC niches, which are functionally supportive of hematopoietic tissue.
authors.affiliation: Dulbecco Telethon Institute, Tettamanti Research Center, Pediatric Department, University of Milano-Bicocca, Monza 20900, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Pievani
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, Rome 00161, Italy.
authors.forename: Benedetto
authors.initials: B
authors.lastname: Sacchetti
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, Rome 00161, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Corsi
authors.affiliation: Pediatric Department, University of Milano-Bicocca, San Gerardo Hospital/Fondazione MBBM, Monza 20900, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Rambaldi
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, Rome 00161, Italy.
authors.forename: Samantha
authors.initials: S
authors.lastname: Donsante
authors.affiliation: Dulbecco Telethon Institute, Tettamanti Research Center, Pediatric Department, University of Milano-Bicocca, Monza 20900, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Scagliotti
authors.affiliation: Department of Obstetrics and Gynecology, University of Milano-Bicocca, Monza 20900, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Vergani
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, Rome 00161, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Remoli
authors.affiliation: Pediatric Department, University of Milano-Bicocca, San Gerardo Hospital/Fondazione MBBM, Monza 20900, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Biondi
authors.affiliation: Skeletal Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
authors.forename: Pamela G
authors.initials: PG
authors.lastname: Robey
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, Rome 00161, Italy serafinim72@gmail.com mara.riminucci@uniroma1.it.
authors.forename: Mara
authors.identifier: 0000-0002-8643-9211
authors.initials: M
authors.lastname: Riminucci
authors.affiliation: Dulbecco Telethon Institute, Tettamanti Research Center, Pediatric Department, University of Milano-Bicocca, Monza 20900, Italy serafinim72@gmail.com mara.riminucci@uniroma1.it.
authors.forename: Marta
authors.identifier: 0000-0001-8105-6476
authors.initials: M
authors.lastname: Serafini
mesh_terms: D000328:Adult; D001854:Bone Marrow Cells / Q000166:cytology*; D002451:Cell Compartmentation; D002648:Child; D005312:Fetal Blood / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology* / Q000637:transplantation; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006706:Homeostasis; D006801:Humans; D009940:Organoids / Q000166:cytology*; D055153:Stem Cell Niche / Q000235:genetics; D017154:Stromal Cells / Q000166:cytology
keywords: Bone marrow organoid; Cord blood-borne fibroblasts; Hematopoietic stem cell niche; Umbilical cord blood