UCLA

Although stem cell therapy holds promises for intractable diseases, its efficacy has been limited by low retention and function of transplanted cells. Two of the key challenges for cell-based therapies are localization and cell function control once injected in a patient. Co-delivery of cells with hydrogels can mitigate these issues by localizing cells at a disease site and enhancing retention. However, the gold standard method, in situ gelation after injection with cells, confines transplanted cells and secreted therapeutic molecules within scaffolds due to the nanoporous nature of the hydrogel mesh. Confined cells are confounded from participating in regeneration, leading to poor outcomes. Moreover, it has been challenging to modulate the biophysical properties of such hydrogels independently from porosity for effective stem cell functional control.

Here we show that microparticle scaffolds that can be co-injected locally with therapeutic cells and assembled in situ to generate a stem cell niche with interconnected microscale pore networks automatically formed in the void space between packed spherical particles. This approach enables enhanced migration and cell-cell connections between cells and transport of therapeutic molecules as well as higher cell proliferation in vitro and retention in vivo. Another key point is the modulation of biophysical properties independently from microporosity. Our scaffold provides a tunable porous environment by changing the physical properties of hydrogel building blocks. Using this platform technology, we demonstrated increased cell activity, such as proliferation and secretion, while the microporosity of the scaffolds induced tissue infiltration and vascularization. This approach achieves localized delivery of stem cells in a non-invasive manner creating a highly-tunable stem cell niche in situ which we envision can advance stem cell therapies as well as other cell-based therapies.