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Published on: October 31, 2012
High plasticity of pediatric adipose tissue-derived stem cells: too much for selective skeletogenic differentiation?
Leonardo Guasti1, Weerapong Prasongchean, Georgios Kleftouris
1Developmental Biology Unit, UCL Institute of Child Health, London UK. p.ferretti@uc.ac.uk
Insights
Pediatric adipose-derived stem cells (ADSCs) exhibit consistent pluripotency and plasticity, differentiating into multiple lineages. Selective cartilage induction requires specific growth factors to avoid bone formation, crucial for therapeutic applications.
Area of Science:
- Regenerative Medicine
- Stem Cell Biology
- Tissue Engineering
Background:
- Adipose-derived stem cells (ADSCs) are a promising source for cell therapy and disease modeling due to tissue accessibility.
- Understanding the consistency and potential of pediatric ADSCs is crucial for developing standardized therapeutic protocols.
- Limited data exists on the phenotype and differentiation potential of stem cells derived from pediatric adipose tissue.
Purpose of the Study:
- To establish and characterize stem cells from pediatric adipose tissue (ADSCs and AEDSCs).
- To investigate the phenotype, pluripotency, and differentiation potential of these cells.
- To address selective cartilage differentiation induction and its implications for clinical applications.
Main Methods:
- Establishing adipose-derived stem cells (ADSCs) and adipose explant dedifferentiated stem cells (AEDSCs) from pediatric patients.
- Utilizing monolayer and micromass cultures to assess cell phenotype and differentiation.
- Employing chondrogenic, osteogenic, adipogenic, and neurogenic induction protocols.
- Investigating selective cartilage differentiation using standard and TGF-β1-containing media.
Main Results:
- Pediatric ADSCs/AEDSCs demonstrated consistent behavior across different patients.
- Cells expressed pluripotency markers and markers for skeletogenic, neural, and adipose lineages, indicating a "lineage-mixed" phenotype.
- Significant plasticity was observed, with cells differentiating and upregulating tissue-specific markers under various induction conditions.
- Selective osteogenic differentiation was achievable, but chondrogenic induction with standard media yielded both cartilage and bone.
Conclusions:
- Pediatric ADSCs possess high plasticity and potential for reprogramming into induced pluripotent stem cells.
- The "lineage-mixed" phenotype of ADSCs contributes to their versatile differentiation capabilities.
- Selective cartilage differentiation requires precise control of induction factors, as standard media can lead to mixed outcomes.
- Simultaneous assessment of bone and cartilage differentiation is essential for bioengineering cartilage for clinical use.
Abstract:
Stem cells derived from adipose tissue are a potentially important source for autologous cell therapy and disease modeling, given fat tissue accessibility and abundance. Critical to developing standard protocols for therapeutic use is a thorough understanding of their potential, and whether this is consistent among individuals, hence, could be generally inferred. Such information is still lacking, particularly in children. To address these issues, we have used different methods to establish stem cells from adipose tissue (adipose-derived stem cells [ADSCs], adipose explant dedifferentiated stem cells [AEDSCs]) from several pediatric patients and investigated their phenotype and differentiation potential using monolayer and micromass cultures. We have also addressed the overlooked issue of selective induction of cartilage differentiation. ADSCs/AEDSCs from different patients showed a remarkably similar behavior. Pluripotency markers were detected in these cells, consistent with ease of reprogramming to induced pluripotent stem cells. Significantly, most ADSCs expressed markers of tissue-specific commitment/differentiation, including skeletogenic and neural markers, while maintaining a proliferative, undifferentiated morphology. Exposure to chondrogenic, osteogenic, adipogenic, or neurogenic conditions resulted in morphological differentiation and tissue-specific marker upregulation. These findings suggest that the ADSC "lineage-mixed" phenotype underlies their significant plasticity, which is much higher than that of chondroblasts we studied in parallel. Finally, whereas selective ADSC osteogenic differentiation was observed, chondrogenic induction always resulted in both cartilage and bone formation when a commercial chondrogenic medium was used; however, chondrogenic induction with a transforming growth factor β1-containing medium selectively resulted in cartilage formation. This clearly indicates that careful simultaneous assessment of bone and cartilage differentiation is essential when bioengineering stem cell-derived cartilage for clinical intervention.
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