University of Toronto’s Armand Keating Lab and CytoSolve Validate a Predictive Systems Architecture for the Mesenchymal Stromal Cell Microenvironment

Institute of Medical Science, University of Toronto – Armand Keating Lab The Armand Keating Lab at the University of Toronto’s Institute of Medical Science is a world-leading group in mesenchymal stromal cell (MSC) biology, regenerative medicine, and clinical translation. The lab is recognized for deep experimental expertise in MSC function, immunomodulation, and therapeutic development across preclinical and clinical contexts.

Challenge

Mesenchymal stromal cells (MSCs) offer substantial therapeutic potential for immune modulation, tissue repair, and regenerative applications, yet clinical trial outcomes have been inconsistent. A central driver of this variability is the MSC microenvironment—an interconnected niche shaped by secreted factors, cell–cell interactions, extracellular matrix cues, and dynamic feedback loops that collectively govern MSC behavior and therapeutic potency.

Traditional experimental approaches produced valuable but fragmented insights, often isolating individual pathways or markers without capturing the full network effects that shape emergent outcomes. The field needed a comprehensive, testable systems architecture of the MSC secretome and niche—one capable of explaining variability across conditions (e.g., inflammation, hypoxia) and guiding optimization strategies for more reliable clinical efficacy.

How CytoSolve Helped

The Keating Lab collaborated with CytoSolve to validate CytoSolve’s computational systems architecture of the MSC microenvironment, using the lab’s extensive MSC datasets and domain expertise as an independent benchmark. CytoSolve’s platform contributed by:

  • Integrating large-scale mechanistic knowledge from thousands of peer-reviewed molecular pathways governing MSC paracrine signaling, immunomodulation, migration, and niche interactions.
  • Generating quantitative, condition-dependent predictions of MSC behavior across key microenvironmental states, including inflammatory and hypoxic contexts relevant to tissue injury and immune disease.
  • Enabling scalable experimental validation, providing a framework to map predicted dynamics to real-world observations from the Keating Lab’s in vitro findings and clinically grounded MSC behavior patterns.

This systems architecture approach moved beyond pathway-by-pathway interpretation to a network-based model designed for falsifiability, iterative refinement, and translational relevance.

Key Benefits Realized

  • Rigorous Peer-Reviewed Validation: Independent confirmation of the full-scale MSC microenvironment architecture through alignment with in vitro and clinical observations.
  • Revealed Hidden Regulatory Mechanisms: Identification of previously unrecognized feedback loops and crosstalk within the MSC secretome influencing potency and persistence.
  • High-Impact Publication: Validation results enabled publication in a prestigious Oxford University Press journal, establishing the architecture as a benchmark for MSC research.
  • Advanced Clinical Translation: Isolation of actionable “control levers” to enhance MSC therapeutic efficacy, informing trial design strategies and biomarker development directions.

Outcome

The Armand Keating Lab, in collaboration with CytoSolve, delivered the first peer-reviewed validation of a comprehensive systems architecture of the MSC microenvironment. Published in an Oxford University Press journal, this milestone clarified molecular drivers underlying MSC function and variability, raised the bar for systems-level rigor in regenerative medicine, and accelerated pathways toward more consistent, effective cell therapies.

Overall, the collaboration demonstrates how CytoSolve’s infrastructure can produce peer-validated, predictive systems models that connect mechanistic biology to experimentally testable insights—supporting high-impact publication outcomes and meaningful progress in translational stem cell medicine.