A novel stem cell therapy is emerging as a potential treatment for frailty, addressing the condition at a biological level. Historically, frailty, a state that increases the risk of falls and infections, has primarily been managed through lifestyle interventions such as strength training and balance exercises.
However, recent findings indicate that administering stem cells from young, healthy individuals to older recipients can significantly enhance their mobility. This innovative approach targets the fundamental biological underpinnings of aging.
“Frailty is a major source of disability and diminished quality of life in older individuals,” stated Joshua Hare, associated with Longeveron, a biotechnology firm based in Miami, Florida. He added, “There is a significant unmet need for biological treatments to address this condition.”
Hare and his Longeveron colleagues are developing a therapy designed to combat some of the aging process’s intrinsic mechanisms. These include inflammation and the decline in metabolic functions responsible for muscle contraction. The treatment, named laromestrocel, consists of mesenchymal stem cells derived from healthy bone marrow donors aged 18 to 45. These cells possess the capacity to differentiate into various cell types, including muscle and cartilage cells.
Clinical Trials and Results
Following positive outcomes in initial frailty trials—a condition affecting approximately one in four individuals aged 65 and older—a larger study involving 148 participants was conducted. This trial evaluated different dosages of laromestrocel against a placebo.
The researchers assessed improvements in the participants’ ability to walk a specific distance over a six-minute period. These participants, aged between 74 and 76, experienced mild to moderate frailty. A single infusion of laromestrocel demonstrated a dose-dependent improvement in their walking performance, with no significant safety concerns noted.
For instance, recipients of the highest laromestrocel dose walked an additional 41 meters compared to the placebo group six months post-infusion. This improvement further increased to 63 meters by the nine-month mark.
Laromestrocel functions by inhibiting enzymes known as matrix metalloproteinases. According to the research team, these enzymes contribute to the degradation of structural proteins within blood vessels and other tissues. Hare explained that this inhibitory action could facilitate the regeneration of the vascular system, which in turn supports muscle fibers involved in endurance activities.
The therapy did not, however, yield improvements in walking speed or grip strength. Hare emphasized the clinical significance of the six-minute walk distance, noting its established correlation with overall health status and longevity.
Daisy Wilson, from the University of Birmingham in the UK, commented on the findings, calling them “very promising.” She expressed particular admiration for the “overall change demonstrated in the 6-minute walk time.”
Potential Biomarker Identification
The trial also may have identified a biomarker for frailty. This potential biomarker could aid in identifying individuals most likely to benefit from the treatment, potentially even before symptoms manifest.
Researchers examined a panel of eight potential biomarkers associated with inflammation and blood vessel formation. Analysis of participant blood samples revealed a progressive decrease in a specific fragment called sTIE2, a marker of impaired vascular function, as laromestrocel dosage increased.
This observation suggests that individuals with elevated sTIE2 levels might gain the most from the therapy, according to Wilson. She elaborated, “Frailty is very heterogeneous. I think the most important part of geroprotector medicine [interventions that slow the aging process] going forward is matching the right patient to the right treatment.”
Challenges and Future Outlook
Wilson also raised practical considerations regarding the cost and feasibility of stem cell therapies. She questioned the cost-effectiveness of such treatments when compared to existing interventions like walking programs, which have shown significant improvements in the six-minute walk test performance. Furthermore, she noted the logistical challenges in obtaining sufficient stem cells from volunteers to treat the broad population affected by frailty.
Hare responded to these concerns by highlighting ongoing technological advancements aimed at scaling up stem cell therapy production. He expressed confidence that efforts to produce these stem cells in large quantities are progressing, assuring that the demand will be met.
Potential Publication: Cell Stem Cell DOI: 10.1016/j.stem.2026.01.017