Drs. Bhatia and Chen review the advances in tissue engineering up to that point, highlighting the potential opportunities for the development of mainstream medical therapies using tissue replacement.
Impact: Marks the beginning of the long-term collaborative effort between the Satellite Bio co-founders to realize the potential of Tissue Therapeutics.
Drs. Bhatia et al. demonstrated, for the first time, in vitro stabilization of parenchymal cells by means of stromal cell co-culture, as demonstrated by long-term albumin secretion by hepatocytes.
Impact: This work from Satellite Bio co-founder, Dr. Bhatia, established that engineering a combination of functional and support cells allows for superior stabilization of cell phenotype compared to previous methods that used a random mixture of cells. The discovery that the interaction between cell types is what is critical provided the foundation for future work to hone heterocellular aggregation, a concept that underlies Satellite Bio’s approach to Tissue Therapeutics.
Advancing on the foundational work published in 1999, Dr. Bhatia’s lab began developing methods for 3D encapsulation of micropatterned primary human cells in hydrogels.
Impact: This proof-of-concept for cell encapsulation, together with the foundational 1999 paper, marks the beginning of the development of Tissue Therapeutics as we know it today.
With a screening technology that enables rapid and reproducible 3D cell structures within a hydrogel, this study demonstrated the parallel formation of >20,000 cell clusters of precise size and shape and the maintenance of high cell viability and differentiated cell markers over two weeks.
Impact: Advancing from 2D analogs, this 3D model demonstrates the importance of precisely controlling the size and shape of cell clusters (now known as Tissue Seeds) to modulate cell-cell interactions within a matrix.
Presents a miniaturized, multiwell culture system for human hepatocytes with optimized microscale architecture that helps maintain phenotype for several weeks. Utility was demonstrated through assessment of gene expression profiles, phase I/II metabolism, canalicular transport, secretion of liver-specific products and susceptibility to hepatotoxins.
Impact: Building on the 1999 work and prior to proof-of-concept, this paper made important progress with heterocellular aggregation, using validated human benchmarks to lay the groundwork for use of a microscale culture of stable, functional human hepatocytes as a therapeutic technology.
Drs. Chen et al. developed the first in vivo mouse model based on the implantation of tissue-engineered human liver, which demonstrated persistence, vascularization, and functional performance for more than three months.
Impact: Through a collaborative effort between the labs of co-founders Drs. Bhatia and Chen, this in vivo model in healthy mice achieved the first proof-of-concept for Tissue Therapeutics, demonstrating that remotely placed engineered liver tissues and the host liver can cooperate, promoting persistence and function. This foundational work enabled future research to advance our understanding of this technology and its applications.
This new approach demonstrated a viable method for rapid casting of patterned vascular networks, overcoming a major challenge for 3D tissue culture.
Impact: This new methodology demonstrated the importance of vascularization in ensuring adequate oxygenation of densely populated 3D tissues to avoid the development of a necrotic core.
Drs. Baranski et al. used an improved pro-vascular methodology in vivo to demonstrate substantially greater hepatic survival and function, as well as host vascular ingrowth.
Impact: This research built on the 2011 findings and demonstrated the critical importance of vascularization to optimize the functional impact of Tissue Therapeutics.
Using enhanced methodologies in mouse models with acute and chronic liver diseases, engineered tissues demonstrated improved vascularization and liver-specific functions. Specifically, tissues containing patterned human primary hepatocytes, endothelial cells, and stromal cells in a degradable hydrogel expanded more than 50-fold over the course of 11 weeks in mice with injured livers. There was a concomitant increase in graft function as indicated by the production of multiple human liver proteins.
Impact: Building on the 2011 work in healthy mice, these preclinical findings demonstrated for the first time that remotely placed engineered tissue – or a Satellite – was a viable approach to treat acute and chronic diseases of the liver. These results, coupled with the significant morbidity and mortality of liver conditions, led Satellite Bio to identify elusive diseases of the liver as an initial opportunity for Tissue Therapeutics.
Drs. Chen et al. developed a new method that enabled assessment of the contribution of stromal cells to the phenotypic stability of primary human hepatocytes and demonstrated the ability to reduce stromal cells while maintaining function.
Impact: More than 20 years later, these findings refined the process of heterocellular aggregation, which closely reflects what we follow today.
Based on their more than two decades of collaborative research across tissue biology and bioengineering, Drs. Bhatia and Chen, along with Arnav Chhabra, PhD, founded Satellite Bio to pioneer Tissue Therapeutics that repair, restore or replace critical organ or tissue function.
Satellite Bio emerged from stealth on April 20, 2022, revealing its first-in-kind Tissue Therapeutics platform, its experienced leadership, and with $110 million in financing from a leading venture syndicate.
