Elucidating and empowering stem cell-chondrocyte interactions for cartilage tissue regeneration
Abstract/Contents
- Abstract
- Cells are social, and dynamic interactions among cells play an important role in tissue development. While stem cells are widely known for their potential to differentiate directly into a variety of cell types, stem cells can also support tissue regeneration by secreting trophic factors to stimulate other cells. Using a 3D hydrogel co-culture model, our lab has previously reported that adipose-derived stem cells (ADSCs) can substantially enhance cartilage tissue regeneration by juvenile chondrocytes, making them become "super chondrocytes", through cell-cell communications. This finding is significant, as it aids in overcoming donor scarcity associated with chondrocytes by mixing them with ADSCs, an abundantly available autologous cell source. However, the molecular mechanisms through which chondrocytes become "super chondrocytes" remain unknown. Furthermore, while using a mixed cell population overcomes the cell source problem, the resulting cartilage remains mechanically weak, with a compressive modulus an order of magnitude lower than that of native cartilage. My thesis seeks to overcome the above two key challenges by: (1) Identifying the key molecular signal changes that drive the "super chondrocyte" phenotype during co-culture, and (2) Improving the mechanical properties of engineered cartilage during co-culture by developing novel 3D scaffolds. Using RNA microarray technology, I compared the gene expression changes during co-culture vs. mono-culture and identified top candidate genes (up-regulation and down-regulation) associated with the "super chondrocyte" phenotype. These targets offer potential new ways to produce "super chondrocytes" via genetic modification, thereby removing the need for co-culture. To further enhance the mechanical properties of tissue engineered cartilage, I developed a new composite scaffold made of macroporous gelatin-based microribbon (µRB)s as well as a rapidly degradable hydrogel. The scaffold was optimized to support initial retention of paracrine signals required for synergistic ADSC-chondrocyte co-culture, but also provide macroporosity to facilitate new tissue formation. When implanted in vivo using a mouse model, the composite scaffold led to a rapid increase in mechanical properties of cartilage produced by mixed ADSCs and chondrocytes, yet minimal increase was observed using conventional hydrogels. Together, the findings from this thesis fill the gap of knowledge of how stem cells catalyze cartilage formation by chondrocytes during co-culture, and will accelerate the translation of using mixed cell populations for cartilage regeneration with enhanced mechanical functions.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2019; ©2019 |
| Publication date | 2019; 2019 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Rogan, Heather Ann Waters |
|---|---|
| Degree supervisor | Yang, Fan, (Bioengineering researcher and teacher) |
| Thesis advisor | Yang, Fan, (Bioengineering researcher and teacher) |
| Thesis advisor | Bhutani, Nidhi |
| Thesis advisor | Smith, R. Lane (Robert Lane) |
| Degree committee member | Bhutani, Nidhi |
| Degree committee member | Smith, R. Lane (Robert Lane) |
| Associated with | Stanford University, Department of Bioengineering. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Heather Ann Waters Rogan. |
|---|---|
| Note | Submitted to the Department of Bioengineering. |
| Thesis | Thesis Ph.D. Stanford University 2019. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2019 by Heather Ann Waters Rogan
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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