Journal article
Human Very Small Embryonic-Like Cells Generate Skeletal Structures, In Vivo
Stem cells and development, Vol.22(4), pp.622-630
09/28/2012
DOI: 10.1089/scd.2012.0327
PMCID: PMC3564465
PMID: 23020187
Abstract
Human very small embryonic-like (hVSEL) cells are a resident population of multipotent stem cells in the bone marrow involved in the turnover and regeneration of tissues. The levels of VSEL cells in blood are greatly increased in response to injury, and they have been shown to repair injured tissues. Adult hVSEL cells, SSEA-4
+
/CD133
+
/CXCR4
+
/Lin
−
/CD45
−
, express the pluripotency markers (Oct-4 and Nanog) and may be able to differentiate into cells from all 3 germ lineages. hVSEL cells isolated from blood by apheresis following granulocyte–colony-stimulating factor mobilization were fractionated and enriched by elutriation and fluorescence activated cell sorting. Collagen sponge scaffolds containing 2,000–30,000 hVSEL cells were implanted into cranial defects generated in SCID mice. Analysis by microcomputed tomography showed that a cell population containing VSEL cells produced mineralized tissue within the cranial defects compared with controls at 3 months. Histologic studies showed significant bone formation and cellular organization within the defects compared with cellular or scaffold controls alone. Antibodies to human leukocyte antigens demonstrated that the newly generated tissues were of human origin. Moreover, human osteocalcin was identified circulating in the peripheral blood. There was evidence that some level of hVSEL cells migrated away from the defect site, using quantitative real-time polymerase chain reaction to detect for human-specific
Alu
sequences. This study demonstrates that hVSEL cells are able to generate human bone tissue in a mouse model of skeletal repair. These studies lay the foundation for future cell-based regenerative therapies for osseous and connective tissue disorders, including trauma and degenerative conditions, such as osteoporosis, fracture repair, and neoplastic repair.
Details
- Title: Subtitle
- Human Very Small Embryonic-Like Cells Generate Skeletal Structures, In Vivo
- Creators
- Aaron M. Havens - University of MichiganYusuke Shiozawa - University of MichiganYounghun Jung - Periodontics and Oral MedicineHongli Sun - University of MichiganJincheng Wang - University of MichiganSamantha McGee - University of MichiganAnjali Mishra - University of MichiganL. Susan Taichman - Periodontics and Oral MedicineTheodora Danciu - Periodontics and Oral MedicineYajuan Jiang - NeostemGregory Yavanian - NeostemElizabeth Leary - NeostemPaul H. Krebsbach - Biomedical Engineering - Medical SchoolDenis Rodgerson - NeostemRussell S. Taichman - Periodontics and Oral Medicine
- Resource Type
- Journal article
- Publication Details
- Stem cells and development, Vol.22(4), pp.622-630
- DOI
- 10.1089/scd.2012.0327
- PMID
- 23020187
- PMCID
- PMC3564465
- NLM abbreviation
- Stem Cells Dev
- ISSN
- 1547-3287
- eISSN
- 1557-8534
- Publisher
- Mary Ann Liebert, Inc
- Language
- English
- Date published
- 09/28/2012
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Craniofacial Anomalies Research Center; Oral and Maxillofacial Surgery
- Record Identifier
- 9984367717102771
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