A blood vessel is not a simple tube. At the smallest scale — the capillary level, where the vessels that tissue engineering most urgently needs to replicate are found — the wall of a microvessel is a precisely organized structure involving at least three distinct cell types, each with a defined functional role. Engineering a system that can guide those cell types to self-assemble into something resembling that structure, under controlled conditions, in a three-dimensional construct, is one of the central technical challenges in vascular tissue engineering.
It is also the biological system that Justin Jadali’s research at Yale University is designed to interrogate. His work uses a multi-cell co-culture model to assess how microparticle-delivered signals influence the formation of microvascular networks in vitro — a model that requires understanding not just one cell type but the relationships between three, and what each contributes to the assembly process.
The Three Cell Types and Their Roles
Endothelial cells are the defining cellular component of blood vessels. They line the interior surface of every vessel in the body — from the aorta to the smallest capillary — and are responsible for forming the selective barrier between circulating blood and surrounding tissue. In vitro, under the right conditions and in the presence of appropriate signals, endothelial cells will organize into tubular structures that recapitulate the geometry of capillary networks. This self-organization capacity is the biological mechanism at the center of therapeutic vascularization strategies.
Pericytes are mural cells — cells that wrap around the outside of capillaries and small venules. They are not simply structural supports. They regulate capillary diameter, modulate endothelial cell proliferation through direct contact and paracrine signaling, and contribute to the stability and maturation of newly formed vessels. In the absence of pericyte coverage, nascent capillary-like structures formed by endothelial cells in culture are unstable: they form but do not persist. Pericyte co-culture is what converts transient tube formation into something that resembles stable microvascular architecture.
Fibroblasts are the principal stromal cells of connective tissue, responsible for synthesizing and remodeling the extracellular matrix — the fibrous, gel-like environment in which vessels are embedded in native tissue. In co-culture systems, fibroblasts contribute matrix components that support endothelial organization, secrete growth factors that promote vessel stability, and provide the extracellular context that makes three-dimensional vascular self-assembly possible. Without them, the co-culture environment lacks the matrix scaffolding that endothelial and mural cells depend on.
Together, these three cell types — endothelial cells, pericytes, and fibroblasts — constitute the minimal cellular system in which meaningful microvascular self-assembly can be studied under controlled in vitro conditions. Each is necessary. None is sufficient alone.
Why Co-Culture Matters for Evaluating a Materials Platform
The purpose of a co-culture model in Jadali’s research is not to produce vessels — it is to assess whether a given materials condition supports the cellular behaviors that lead to vessel formation. The microparticle system he is developing delivers bioactive signals into the co-culture environment from within a hydrogel matrix, and the co-culture assay is the measurement instrument: it reveals whether those signals, at the concentrations and time scales produced by a given particle formulation, are sufficient to drive endothelial self-organization and whether the resulting structures are stabilized by pericyte interaction.
This makes the co-culture model both a read-out system and a constraint. It is a read-out in the sense that changes in microvessel network formation — measured through microscopy of the assembled cell structures — reflect the biological effect of different particle formulations. It is a constraint in the sense that the model is only informative if the three-cell system is functioning as expected: if pericytes are not providing stabilization or fibroblasts are not contributing appropriate matrix signals, the assay cannot distinguish between a material that failed to deliver signals and a co-culture that failed to respond to them.
Maintaining a reliable co-culture assay therefore requires the same protocol rigor that Jadali applies to the fabrication side of his research: consistent cell sourcing, defined passage numbers, controlled seeding densities, and careful monitoring of culture conditions across experiments.
What Microscopy Reveals — and What It Requires
The primary instrument for assessing microvascular self-assembly in co-culture is fluorescence microscopy. Cells are labeled — either through transgenic fluorescent protein expression or through immunostaining for endothelial-specific markers — and imaged at defined time points to visualize the degree of tube formation, network connectivity, and vessel stability across experimental conditions.
Quantifying those images in a way that is reproducible and comparable across conditions is a non-trivial task. It requires establishing consistent imaging parameters, applying defined image analysis workflows, and selecting quantitative metrics — network length, branch point density, vessel diameter distribution — that capture the relevant biological differences between conditions without introducing operator-dependent variability.
Jadali’s hands-on microscopy experience, developed alongside his cell culture and fabrication work at Yale, is directly relevant here. The ability to produce high-quality, quantifiable microscopy data from a co-culture assay is as important to the research as the ability to fabricate consistent microparticle batches. Both are skills that take time to develop and that cannot be substituted by theoretical knowledge of the underlying biology or materials science.
The Significance of In Vitro Vascularization Models
The three-cell co-culture model Jadali employs reflects a broader shift in tissue engineering research toward more physiologically representative in vitro systems. Early vascularization assays used endothelial cells alone, in two-dimensional culture on gel substrates. These systems demonstrated that endothelial cells could form tube-like structures but did not capture the stabilizing influence of mural cells or the matrix contributions of stromal fibroblasts — both of which are present in native tissue and both of which are necessary for vessel maturation.
Moving to three-cell, three-dimensional co-culture systems increased experimental complexity substantially. They require more cell types, more controlled culture conditions, and more sophisticated imaging and analysis pipelines. But they produce biological information that the simpler systems cannot: information about vessel stability, not just vessel initiation; information about matrix remodeling, not just cell organization; and information about the interplay between material-delivered signals and the multicellular environment that will ultimately determine whether a therapeutic strategy works in vivo.
The rigor of using a three-cell model to evaluate his microparticle system is a deliberate choice that reflects the kind of research Justin Jadali is doing at Yale — not the minimum required to publish a finding, but the system needed to produce findings that will hold up under the more demanding conditions of the next experimental stage.
A Platform Built for the Questions That Follow
The co-culture model is not just a measurement tool for the current set of experiments. It is a platform that can be used to evaluate future modifications to the microparticle system — changes in factor loading, crosslinker identity, particle size, or degradation rate — using the same biological read-out, under the same conditions, with results that are directly comparable to what has already been established.
That comparability is what makes a research platform durable. Individual experiments answer individual questions. A well-validated platform answers families of questions, each building on the last. Justin Jadali’s work at Yale — combining rigorous microparticle fabrication with a three-cell co-culture model and quantitative microscopy — is constructing that platform, one experimentally characterized condition at a time.
About Justin Jadali
Justin Jadali is a mechanical engineer and biomedical engineering researcher currently completing his M.S. in Mechanical Engineering and Materials Science at Yale University. He earned his B.S. in Mechanical Engineering from UCLA as part of the Class of 2025, following three Associate of Science degrees in Physics, Mathematics, and Natural Sciences from Irvine Valley College. At Yale, his research focuses on alginate microparticle fabrication, crosslinking systems, and the quantification of microvessel self-assembly in three-dimensional tissue constructs. He has hands-on experience in polymer processing, cell culture, and microscopy workflows, and has served as a teaching assistant for the Yale mechanical engineering capstone. He is also the founder of an e-commerce company that he grew to approximately 10 employees before selling at a six-figure valuation.
