ISCT Mesenchymal Stromal Cell (MSC) Committee
Mesenchymal stromal cells (MSCs) are among the most widely used cellular products worldwide, yet the field still lacks shared, testable answers about what happens to these cells after administration. A new ISCT MSC Committee-led perspective (https://doi.org/10.1016/j.jcyt.2025.102007) outlines key knowledge gaps and experimental strategies needed to address them.
The Questions Every Living Cell Product Must Answer
For MSCs, these questions have remained especially persistent. MSCs are being investigated across a broad range of disease indications and delivery routes, yet their in vivo fate, clearance, persistence, host interactions, and the consequences of those events remain incompletely understood. This gap has important downstream implications: it complicates interpretation of clinical outcomes, limits cross-trial comparability and slows progress in next-generation MSC product development.
To address these challenges, the ISCT MSC Committee convened an international group of experts for an online workshop aimed at moving the conversation beyond long-standing debate toward a clearer and more actionable research agenda. The group reviewed current evidence, identified critical unanswered questions, and proposed practical experimental paths forward.
A New Cytotherapy Perspective: What We Know, What We Don't, and What to Do Next
The outcome of this workshop is a new open-access perspective published in Cytotherapy: “Fate and function of exogenously administered mesenchymal stromal cells: current insights and future directions.”
The paper focuses on three core domains relevant across CGT, examined here through the specific biological and translational context of MSCs.
- Systemic delivery: biodistribution and mechanism of action
After systemic administration, MSCs encounter a highly reactive biological environment. Multiple clearance-related processes have been documented, including instant blood-mediated inflammatory reaction (IBMIR), coagulation and complement activation, and downstream immune engagement. However, the relative contribution of these events to MSC “function” remains unclear.
An important theme emerging from the workshop was that “clearance” should not automatically be viewed as therapeutic failure. If apoptosis, efferocytosis (clearance by phagocytes), or interactions at vascular barriers contribute to immune modulation, then the more relevant question becomes which clearance pathways matter, under what conditions, and in which delivery context.
- Local or depot-based delivery: context changes everything
Local administration may alter the balance between persistence, containment, and interaction with tissue-resident immune and stromal cells. Workshop discussions highlighted how delivery context influences both what can be measured and what should be measured, particularly when the intended biological effects are local, regional, or mediated indirectly through host responses rather than long-term engraftment.
- Persistence and clearance: beyond “cell tracking”
One of the strongest recurring themes was the need to move beyond simply asking “Where are the cells?” as the end goal. Traditional tracking approaches remain informative, but they often fall short of answering questions most relevant to developers and clinicians, including functional persistence, temporal immune modulation, and the relationship between delivery route, clearance pathways, and downstream biology.
A major focus of both the workshop and the resulting perspective was MSC apoptosis and its immunological consequences, particularly interactions between apoptotic MSCs, phagocytes, and endothelial barriers.
What the MSC Committee is Trying to Accomplish
The ISCT MSC Committee aims to do more than simply “summarise the field.” Through this initiative, the committee sought to identify fundamental biological questions that have remained elusive, as well as key barriers limiting successful clinical translation of MSC products.
This workshop-and-publication model represents one approach to transforming complex and sometimes polarised discussions into a shared framework that can be tested, challenged, and refined collaboratively.
Why the Broader ISCT Community Should Pay Attention
Even for those outside the MSC field, many of the themes discussed are broadly relevant across CGT:
- Biology meets delivery reality. In vivo performance is shaped by route, host environment, and early interactions that can be easy to overlook in vitro.
- Mechanism needs measurable anchors. Without agreed experimental strategies, the field risks generating descriptive data that fail to translate into actionable guidance.
- Comparability matters. Shared definitions and reproducible approaches make it easier to compare results across groups, platforms, and disease indications.
This perspective is not intended to serve as a final word. Rather, it represents a deliberate attempt to define the most urgent knowledge gaps and propose practical strategies that can help move the field from inference toward evidence.
Next Stop: Continuing the Conversation in Dublin
To build on these discussions, the MSC Committee planned a follow-up, invitation-only workshop involving committee members and global MSC experts at the ISCT 2026 Annual Meeting in Dublin (May 6–9, 2026).
The goal is straightforward: bring the community into the next step, pressure-test the proposed research questions, identify tractable near-term experiments, and explore where shared resources or collaborations could accelerate progress.
Progress in this area is unlikely to come from a single “perfect” tracking method. Rather, it will depend on asking better-defined questions, applying stronger experimental logic, and fostering a community willing to openly compare approaches and findings.
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