Institute Affiliations

Stanford Advisors

Contact

  • Academic
    carlahl@stanford.edu
    University - Scholar Department: Materials Science and Engineering Position: Postdoctoral Scholar

Additional Info

  • Mail Code: 4045

All Publications

  • Viscoelastic N‑cadherin-like interactions maintain neural progenitor cell stemness within 3D matrices. Nature communications Huang, M. S., LeSavage, B. L., Ghorbani, S., Gilchrist, A. E., Roth, J. G., Huerta-López, C., Mozipo, E. A., Navarro, R. S., Heilshorn, S. C. 2025; 16 (1): 5213

    Abstract

    Neural progenitor cells (NPCs) hold immense potential as therapeutic candidates for neural regeneration, and materials-based strategies have emerged as attractive options for NPC expansion. However, maintaining NPC stemness has proven challenging in vitro, due to their propensity to form cell-dense neurospheres. While neurospheres promote cell-cell interactions required for NPC stem maintenance, they also restrict oxygen transport, leading to hypoxia and limited cell expansion. To overcome these limitations, we investigate two materials-based approaches to maintain NPC stemness: 1) physical matrix remodeling within a viscoelastic, stress-relaxing hydrogel and 2) matrix-induced N-cadherin-like signaling through a cell-instructive peptide. While viscoelasticity alone is sufficient to maintain NPC stemness compared to an elastic environment, NPCs still preferentially form neurospheres. The addition of N-cadherin-like peptides promotes a distributed culture of NPCs while maintaining their stemness through cadherin-mediated signaling, ultimately exhibiting improved long-term expansion and neural differentiation. Thus, our findings reveal matrix viscoelasticity and engineered N-cadherin-like interactions as having a synergistic effect on NPC expansion and differentiation within 3D matrices.

    View details for DOI 10.1038/s41467-025-60540-8

    View details for PubMedID 40473615

    View details for PubMedCentralID 5682670

  • Engineered matrices reveal stiffness-mediated chemoresistance in patient-derived pancreatic cancer organoids. Nature materials LeSavage, B. L., Zhang, D., Huerta-López, C., Gilchrist, A. E., Krajina, B. A., Karlsson, K., Smith, A. R., Karagyozova, K., Klett, K. C., Huang, M. S., Long, C., Kaber, G., Madl, C. M., Bollyky, P. L., Curtis, C., Kuo, C. J., Heilshorn, S. C. 2024

    Abstract

    Pancreatic ductal adenocarcinoma (PDAC) is characterized by its fibrotic and stiff extracellular matrix. However, how the altered cell/extracellular-matrix signalling contributes to the PDAC tumour phenotype has been difficult to dissect. Here we design and engineer matrices that recapitulate the key hallmarks of the PDAC tumour extracellular matrix to address this knowledge gap. We show that patient-derived PDAC organoids from three patients develop resistance to several clinically relevant chemotherapies when cultured within high-stiffness matrices mechanically matched to in vivo tumours. Using genetic barcoding, we find that while matrix-specific clonal selection occurs, cellular heterogeneity is not the main driver of chemoresistance. Instead, matrix-induced chemoresistance occurs within a stiff environment due to the increased expression of drug efflux transporters mediated by CD44 receptor interactions with hyaluronan. Moreover, PDAC chemoresistance is reversible following transfer from high- to low-stiffness matrices, suggesting that targeting the fibrotic extracellular matrix may sensitize chemoresistant tumours. Overall, our findings support the potential of engineered matrices and patient-derived organoids for elucidating extracellular matrix contributions to human disease pathophysiology.

    View details for DOI 10.1038/s41563-024-01908-x

    View details for PubMedID 38965405

    View details for PubMedCentralID 5704175