Osteogenic differentiation of two distinct subpopulations of human adipose-derived stem cells: an in vitro and in vivo study

Rada, Tommaso; Santos, T. C.; Marques, A. P.; Correlo, V. M.; Frias, A. M.; Neves, Nuno M.; Gomes, Manuela E.; Reis, Rui L.

doi:10.1002/term.388

Cited by 45 publications

(34 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As has been reported previously, adipose tissue contains ASC subpopulations with distinct differentiation potentials (12,15,(33)(34)(35). Surface antigen expression has been used to detect subpopulations capable of lineage-specific differentiation.…”

Section: Discussionmentioning

confidence: 88%

Cellular mechanical properties reflect the differentiation potential of adipose-derived mesenchymal stem cells

González-Cruz

Fonseca²,

Darling³

2012

Proc. Natl. Acad. Sci. U.S.A.

193

153

View full text Add to dashboard Cite

The mechanical properties of adipose-derived stem cell (ASC) clones correlate with their ability to produce tissue-specific metabolites, a finding that has dramatic implications for cell-based regenerative therapies. Autologous ASCs are an attractive cell source due to their immunogenicity and multipotent characteristics. However, for practical applications ASCs must first be purified from other cell types, a critical step which has proven difficult using surface-marker approaches. Alternative enrichment strategies identifying broad categories of tissue-specific cells are necessary for translational applications. One possibility developed in our lab uses single-cell mechanical properties as predictive biomarkers of ASC clonal differentiation capability. Elastic and viscoelastic properties of undifferentiated ASCs were tested via atomic force microscopy and correlated with lineage-specific metabolite production. Cell sorting simulations based on these "mechanical biomarkers" indicated they were predictive of differentiation capability and could be used to enrich for tissue-specific cells, which if implemented could dramatically improve the quality of regenerated tissues.cell mechanics | mesenchymal stem cell enrichment | viscoelasticity | single-cell characterization | AFM A dipose tissue contains a heterogeneous population of mesenchymal stem cells (MSCs) known as adipose-derived stem cells (ASCs) (1). ASCs are capable of differentiating into a variety of lineage-specific cell types, including adipocytes, osteoblasts, and chondrocytes (1-3). In comparison to MSCs derived from other tissues, ASCs are simple to isolate and available in large quantities (4, 5). Because of the cells' mesodermal origin, ASCs have been used for many soft tissue and orthopaedic applications (6-10). Unfortunately, ASC isolation is confounded by the lack of distinct and universally effective MSC biomarkers. Adipose tissue contains multiple cell types, including mature adipocytes, fibroblasts, smooth muscle cells, and endothelial cells (11), which can contaminate the stromal fraction collected during ASC isolation. While conventional methods such as flow cytometry can isolate stem cells using surface antigen expression (1, 2, 12), resulting cell yields are often less than 1% (13,14). Furthermore, the surface antigens present on ASCs can also be found on other cell types in adipose tissue, complicating the isolation of pure mesenchymal stem cell populations (15-17). Collectively, these limitations suggest a need for alternative biomarkers that allow for ASC enrichment based on lineage potential.Recently, single-cell mechanical properties were found to be akin to gene and protein expressions, capable of distinguishing differences in cellular subpopulations, disease state, and tissue source (18)(19)(20)(21)(22). Cells display varying levels of resistance to deformation (elasticity) and flow (viscosity) in response to an applied force. This behavior depends on the composition and organization of subcellular structures, particularly the cytosk...

show abstract

Section: Discussionmentioning

confidence: 88%

Cellular mechanical properties reflect the differentiation potential of adipose-derived mesenchymal stem cells

González-Cruz

Fonseca²,

Darling³

2012

Proc. Natl. Acad. Sci. U.S.A.

193

153

View full text Add to dashboard Cite

show abstract

“…It remains to be determined whether the SSEA4 + /CD73 + and SSEA4 − /CD73 + subpopulations exhibit different functional differentiation. Phenotypic differences in surface markers and gene profiling are recognized to influence the regenerative properties of different BMSC subpopulations (22)(23)(24), and could explain the differences observed with the hiPSC-derived progenitors used in this study.…”

Section: Resultsmentioning

confidence: 99%

Engineering bone tissue substitutes from human induced pluripotent stem cells

Peppo

Marcos-Campos

Kahler

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

189

199

View full text Add to dashboard Cite

Congenital defects, trauma, and disease can compromise the integrity and functionality of the skeletal system to the extent requiring implantation of bone grafts. Engineering of viable bone substitutes that can be personalized to meet specific clinical needs represents a promising therapeutic alternative. The aim of our study was to evaluate the utility of human-induced pluripotent stem cells (hiPSCs) for bone tissue engineering. We first induced three hiPSC lines with different tissue and reprogramming backgrounds into the mesenchymal lineages and used a combination of differentiation assays, surface antigen profiling, and global gene expression analysis to identify the lines exhibiting strong osteogenic differentiation potential. We then engineered functional bone substitutes by culturing hiPSCderived mesenchymal progenitors on osteoconductive scaffolds in perfusion bioreactors and confirmed their phenotype stability in a subcutaneous implantation model for 12 wk. Molecular analysis confirmed that the maturation of bone substitutes in perfusion bioreactors results in global repression of cell proliferation and an increased expression of lineage-specific genes. These results pave the way for growing patient-specific bone substitutes for reconstructive treatments of the skeletal system and for constructing qualified experimental models of development and disease.

show abstract

“…10 Positive STRO-1 staining may indicate secretion of bone matrix and of cementoid and dentinoid material. 19 STRO-1 has been associated with increased osteogenic capacity 20 and is a marker of stem cells. 21 Studies have demonstrated STRO-1 expression around vessels as well in the pulp 22 and also in pyogenic granuloma and POF.…”

Section: Discussionmentioning

confidence: 99%

The role of Osterix protein in the pathogenesis of peripheral ossifying fibroma

et al. 2017

View full text Add to dashboard Cite

Peripheral ossifying fibroma (POF) is a reactive lesion of oral tissues, associated with local factors such as trauma or presence of dental biofilm. POF treatment consists of curettage of the lesion combined with root scaling of adjacent teeth and/or removal of other sources of irritants. This study aimed to analyze the clinical and pathological features of POF and to investigate the immunoexpression of Osterix and STRO-1 proteins. Data such as age, gender, and size were obtained from 30 cases of POF. Microscopic features were assessed by conventional light microscopy using hematoxylin-eosin staining and immunohistochemical markers, and by polarized light microscopy using Picrosirius red staining. The age range was 11-70 years and 70% of the patients were female. Moreover, the size of POF varied from 0.2 to 5.0 cm; in 43.33% of the cases, the mineralized content consisted exclusively of bony trabeculae. The immunohistochemical analysis showed nuclear staining for Osterix in 63% and for STRO-1 in 20% of the cases. Mature collagen fibers were observed in mineralized tissue in 76.67% of the cases. The clinical and microscopic features observed were in agreement with those described in the literature. Osterix was overexpressed, while STRO-1 was poorly expressed. Osterix was expressed particularly in cells entrapped in and around mineralized tissue, indicating the presence of a stimulus that triggers the differentiation of these cells into osteoblasts or cementoblasts, i.e., cells that produce mineralized tissue. Based on our results, Osterix may play a role in the pathogenesis of POF.

show abstract

Osteogenic differentiation of two distinct subpopulations of human adipose-derived stem cells: an in vitro and in vivo study

Cited by 45 publications

References 54 publications

Cellular mechanical properties reflect the differentiation potential of adipose-derived mesenchymal stem cells

Cellular mechanical properties reflect the differentiation potential of adipose-derived mesenchymal stem cells

Engineering bone tissue substitutes from human induced pluripotent stem cells

The role of Osterix protein in the pathogenesis of peripheral ossifying fibroma

Contact Info

Product

Resources

About