ISCT Mesenchymal Stroma 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 they are administered/delivered. A new ISCT MSC Committee-led perspective outlines the most urgent research/knowledge gaps and the experimental strategies needed to close them.
The Questions Every Living Cell Product Must Answer
For MSCs, these questions have been especially persistent. MSCs are being investigated across a wide range of disease indications and administration/delivery routes, but in vivo fate, clearance, persistence, host interactions, and the consequences of those events remain incompletely understood. That gap has real downstream effects: it complicates interpretation of clinical outcomes, makes cross-trial comparisons difficult, and slows progress on next-generation drug product design.
The ISCT MSC Committee convened an international group of experts for an online workshop to transform the conversation from a long-running debate toward a clearer, shared research agenda. The expert group reviewed the current evidence, identified the most pressing 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 online expert workshop is a new open-access perspective in Cytotherapy: “Fate and function of exogenously administered mesenchymal stromal cells: current insights and future directions.”
The paper is built around three core domains that will feel familiar to many working across CGT, but here, they are framed specifically through the MSC-specific context and tied to concrete experimental recommendations:
- Systemic delivery: biodistribution and mechanism of action
After systemic administration, MSCs encounter a highly reactive environment. The field has documented multiple clearance-related processes, instant blood-mediated inflammatory reaction (IBMIR), activation of coagulation and complement, and downstream immune engagement, but the relative contribution of these events to MSC “function” is still being worked out.
A key point is that “clearance” should not automatically be treated as failure. If apoptosis, efferocytosis (clearance by phagocytes), or interactions at vascular barriers shape immune modulation, then the relevant question becomes: which clearance pathways matter, when, and in what delivery context?
- Local or depot-based delivery: context changes everything
Local administration can shift the balance between persistence, containment, and interaction with tissue-resident immune and stromal cells. The workshop discussions highlighted how delivery context influences both what can be measured and what should be measured, particularly when the intended biological effect is local, regional, or mediated through secondary host responses rather than long-term engraftment.
- Persistence and clearance: beyond “cell tracking”
One of the most consistent themes was the need to move beyond “where are the cells?” tracking as the end goal. Traditional tracking approaches can be informative, but they often stop short of answering what drug developers and clinicians actually need to know: functional persistence, immune modulation over time, and the relationship between delivery route, clearance pathways, and downstream biology.
A major focus of the meeting and the perspective was MSC apoptosis and its immunological consequences, including interactions between apoptotic MSCs, phagocytes, and endothelial barriers.
What the MSC Committee is Trying to Accomplish
The ISCT MSC Committee exists to do more than “summarise the field.” In practical terms, with this paper, we wanted to identify fundamental biological questions that have remained elusive, as well as key barriers to successful translation of MSC products.
This workshop-and-paper model is one way the MSC scientific committee is trying to turn complex, and sometimes polarised, topics into a shared plan that can be tested, critiqued, and refined.
Why the Wider ISCT Community Should Pay Attention
Even if MSCs are not your day-to-day focus, the themes here map onto challenges shared 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, we risk repeating descriptive studies that don’t 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 as a final word. It is a deliberate attempt to define the most urgent knowledge gaps and propose strategies that can move the field from inference to evidence.
Next Stop: Continuing the Conversation in Dublin
To continue the advances, the MSC Committee has planned a follow-up, invitation-only workshop of committee members and MSC global 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 align on where shared resources or collaborations could accelerate progress.
Progress here won’t come from a single “perfect” tracking method. It will come from better-defined questions, stronger experimental logic, and a community willing to compare notes openly/honestly.
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