Stem Cell Therapy Laromestrocel Boosts Walking Ability in Frail Older Adults

Aging frailty is a clinical syndrome characterized by declining physical function, hypomobility, and increased vulnerability to adverse health outcomes. Despite affecting millions of older adults worldwide, no approved pharmacological or biological therapy exists for frailty. This trial addressed that gap by testing laromestrocel — allogeneic human bone marrow-derived mesenchymal stem cells (MSCs) — in a randomized, dose-escalation design. The rationale rests on MSCs' known immunomodulatory and paracrine signaling properties, which may counteract the chronic low-grade inflammation (inflammaging) and vascular dysfunction underlying frailty progression.

The LARA trial (ClinicalTrials.gov NCT03169231) enrolled 148 ambulatory adults meeting clinical frailty criteria across multiple Florida sites. Participants were randomized to placebo or escalating doses of laromestrocel administered as intravenous infusions. The primary endpoint was change in 6-minute walk test (6MWT) distance — a validated, clinically meaningful measure of physical functioning in older adults. Secondary endpoints included the PROMIS physical function patient-reported outcome measure and circulating biomarkers including soluble TIE-2 (sTIE-2), a shed ectodomain of the angiopoietin receptor involved in vascular integrity and angiogenesis.

At 9 months, laromestrocel-treated participants demonstrated a 63.4-meter improvement in 6MWT distance versus placebo (95% CI: 17.1–109.6 m; p=0.0077), exceeding the commonly accepted minimal clinically important difference for this measure in frail older adults. At 6 months, the improvement was 41.3 meters (95% CI: −2.4–84.9 m; p=0.0635), trending toward significance. The dose-dependent and time-dependent nature of the benefit suggests the therapeutic effect builds progressively, consistent with MSC mechanisms involving sustained paracrine activity rather than direct tissue engraftment.

Importantly, improvements in 6MWT distance correlated significantly with PROMIS physical function scores, indicating that the objective walking gains translated into meaningful patient-perceived functional improvement. On the biomarker side, increasing doses of laromestrocel were associated with decreases in soluble (degraded) TIE-2 in circulation. Since elevated sTIE-2 reflects disrupted angiopoietin signaling and vascular inflammation, its reduction provides a mechanistic link between MSC infusion, restored vascular homeostasis, and improved physical performance — and positions sTIE-2 as a candidate pharmacodynamic biomarker for future trials.

The safety profile across dose groups was acceptable, with no treatment-related serious adverse events attributed to laromestrocel, consistent with the allogeneic MSC safety record established in prior cardiovascular and inflammatory disease trials. From a clinical standpoint, these findings are significant: they demonstrate that a single-course intravenous stem cell infusion can produce durable functional gains in frail older adults lasting at least 9 months. For clinicians managing geriatric patients with hypomobility and declining physical reserve, laromestrocel represents a potentially transformative approach pending phase 3 confirmation. Caveats include the relatively small sample size, the single-geographic recruitment pool, and the need for larger trials to confirm optimal dosing regimens and longer-term durability.