In a collaborative research endeavor, UT Austin Department of Biomedical Engineering professors Janet Zoldan and Nicholas Peppas received a grant from the National Institutes of Health to spearhead the development of an in vitro hydrogel culturing system for the ex-vivo expansion of hematopoietic stem cells (HSCs) derived from human induced pluripotent stem cell lines.

Why The Research Matters

In 2018, a staggering 23,000 Hematopoietic Stem Cell (HSC) transplants, crucial for treating myeloma and leukemia, were performed in the United States. Yet, the efficacy of these transplants hinges on the quantity of HSCs delivered to the patient. Developing innovative in vitro expansion techniques is critical, especially considering HSCs' rarity and their intricate relationship with the HSC niche. Creating a hydrogel system mirroring the bone marrow niche is paramount.

This system can boost HSC survival, proliferation, and differentiation. The end result revolutionizes the success rate of bone marrow and stem cell transplants.

About the Research

While in vitro studies employing synthetic hydrogels as artificial matrices shed light on the environmental regulation of HSC behavior, the unescapable correlation between stiffness and solute diffusivity in synthetic hydrogels obscured the precise governing mechanisms dictating HSC responses. Notably, this limited control over the physical properties of hydrogels poses obstacles to the establishment of robust methodologies for in vitro HSC expansion.

In response to these challenges, Zoldan and Peppas proposed an innovative structural approach to hydrogel design. This approach aims to effectively decouple the mechanical stiffness and solute transport properties within a biocompatible hydrogel that mimics the HSC niche. This culturing system will unveil the intricate biophysical factors influencing HSC survival and differentiation and ultimately create a conducive environment for successful in vitro HSC culture and expansion.

Research Goals

These groundbreaking efforts will lead to the development of a comprehensive culture system for in vitro expansion of self-renewing HSCs that will reduce donor morbidity and expand access to HSC transplants as a curative therapy for HSC associated cancers and genetic disorders.