Hypoxia impedes hypertrophic chondrogenesis of human multipotent stromal cells.
Summary of "Hypoxia impedes hypertrophic chondrogenesis of human multipotent stromal cells."
Within the field of bone tissue engineering, the endochondral approach to forming bone substitutes represents a novel concept, where cartilage will undergo hypertrophic differentiation prior to conversion into bone. For this purpose, clinically relevant multipotent stromal cells, MSCs, can be differentiated into the chondrogenic lineage before stimulating hypertrophy. Controversy remains in literature on the oxygen tensions naturally present during this transition in for example the growth plate. Therefore, the present study focused on the effects of different oxygen tensions on the progression of hypertrophic differentiation of MSCs. Bone marrow-derived MSCs of four human donors were expanded and differentiation was induced in aggregate cultures. Normoxic (20% oxygen) and hypoxic (5%) conditions were imposed on the cultures in chondrogenic or hypertrophic differentiation media. After 4 weeks, cultures were examined histologically and by real-time PCR. Morphological assessment showed chondrogenic differentiation of cultures from all donors under normoxic chondrogenic conditions. Additionally, hypertrophic differentiation was observed in cultures derived from all but one donor. Deposition of collagen type X was evidenced in both chondrogenically and hypertrophically stimulated cultures. However, mineralization was exclusively observed in hypertrophically stimulated, normoxic cultures. Overall, the progression of hypertrophy was delayed in hypoxic compared to normoxic groups. The observed delay was supported by the gene expression patterns, especially showing upregulation of late hypertrophic markers osteopontin and osteocalcin under normoxic hypertrophic conditions. Concluding, normoxic conditions are more beneficial for hypertrophic differentiation of MSCs than hypoxic conditions, as long as the MSCs possess hypertrophic potential. This finding has implications for cartilage tissue engineering as well as endochondral bone tissue engineering, as these approaches deal with, respectively, inhibition or enhancement of hypertrophic chondrogenesis.
University Medical Center Utrecht, Orthopaedics, Heidelberglaan 100, G05.228, PO Box 85500, Utrecht, Netherlands, 3508GA, =31 88 755 8078; D.Gawlitta@umcutrecht.nl.
This article was published in the following journal.
Name: Tissue engineering. Part A
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22563686
- DOI: http://dx.doi.org/10.1089/ten.TEA.2011.0657
Medical and Biotech [MESH] Definitions
Endometrial Stromal Tumors
Neoplasms of the endometrial stroma that sometimes involve the MYOMETRIUM. These tumors contain cells that may closely or remotely resemble the normal stromal cells. Endometrial stromal neoplasms are divided into three categories: (1) benign stromal nodules; (2) low-grade stromal sarcoma, or endolymphatic stromal myosis; and (3) malignant endometrial stromal sarcoma (SARCOMA, ENDOMETRIAL STROMAL).
A malignant kidney tumor, caused by the uncontrolled multiplication of renal stem (blastemal), stromal (STROMAL CELLS), and epithelial (EPITHELIAL CELLS) elements. However, not all three are present in every case. Several genes or chromosomal areas have been associated with Wilms tumor which is usually found in childhood as a firm lump in a child's side or ABDOMEN.
Connective Tissue Growth Factor
A CCN protein family member that regulates a variety of extracellular functions including CELL ADHESION; CELL MIGRATION; and EXTRACELLULAR MATRIX synthesis. It is found in hypertrophic CHONDROCYTES where it may play a role in CHONDROGENESIS and endochondral ossification.
Multipotent Stem Cells
Specialized stem cells that are committed to give rise to cells that have a particular function; examples are MYOBLASTS; MYELOID PROGENITOR CELLS; and skin stem cells. (Stem Cells: A Primer [Internet]. Bethesda (MD): National Institutes of Health (US); 2000 May [cited 2002 Apr 5]. Available from: http://www.nih.gov/news/stemcell/primer.htm)
Bone Marrow Cells
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
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