Stem cells are gaining attention for their potential to treat leukemia, certain solid tumor cancers, and inherited metabolic disorders. Now, a clinical trial reports that a single dose can significantly improve physical strength and key signs of aging in older adults with frailty.
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Clinical and Translational ReportVolume 33, Issue 3p393-404.e4March 05, 2026

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Randomized phase 2b dose-escalation trial of stem cell therapy with laromestrocel for aging frailty

Jorge G. Ruiz^1,2,17 ∙ Anthony A. Oliva, Jr.^3,17 ∙ Kevin N. Ramdas³ ∙ … ∙ Zarin Zainul³ ∙ Brian G. Rash³ ∙ Joshua M. Hare^3,16,19 [email protected] … Show more

Affiliations & Notes

1Memorial Healthcare System, Hollywood, FL, USA

2Florida Atlantic University Schmidt College of Medicine, Boca Raton, FL, USA

3Longeveron Inc., Miami, FL, USA

4Advanced Research for Health Improvement, LLC, Naples, FL, USA

5Clinical Research of South Florida, Coral Gables, FL, USA

6Panax Clinical Research, Miami Lakes, FL, USA

7Vista Health Research, LLC, Miami, FL, USA

8Clinical Physiology Associates, Ft. Myers, FL, USA

9Johns Hopkins University, Baltimore, MD, USA

10National Center for Geriatrics and Gerontology, Obu, Japan

11Sealy Center on Aging, University of Texas Medical Branch, Galveston, TX, USA

12Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

13Pharma Data Associates LLC, Piscataway, NJ, USA

14Miami VA Healthcare System Geriatric Research, Education and Clinical Center (GRECC), Miami, FL 33125, USA

15Provonix, Sewell, NJ 08080, USA

16Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA

17

These authors contributed equally

18

Deceased

19

Lead contact

Article Info

Publication History:

Received September 7, 2025; Revised December 12, 2025; Accepted January 28, 2026; Published online February 25, 2026

DOI: 10.1016/j.stem.2026.01.017 External LinkAlso available on ScienceDirect External Link

Copyright: © 2026 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Published: February 25, 2026

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Highlights

•

Performance on the 6-minute walk test improved in a dose-response fashion

•

Improved 6-minute walk test distance correlated with patient-reported outcomes

•

The percentage of study subjects classified as frail decreased by month 9

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Decreased soluble TIE2 in blood may reflect improved vascular function and inflammaging

Summary

Frailty, a syndrome that decreases healthspan in older individuals, lacks effective therapies. We conducted a randomized, dose-finding clinical trial to test whether human bone marrow-derived allogeneic mesenchymal stem cells (MSCs; laromestrocel) improve physical functioning and patient self-reported outcomes in ambulatory individuals with frailty (ClinicalTrials.gov #NCT03169231; N = 148). Laromestrocel infusion results in clinically meaningful, dose- and time-dependent increases in the 6-min walk test (6MWT; primary endpoint) compared with placebo: 63.4 m (95% confidence interval [CI]: 17.1–109.6 m; p = 0.0077) at month 9 and 41.3 m (95% CI: −2.4–84.9 m; p = 0.0635) at month 6. Increased 6MWT distance correlates with PROMIS Physical Function score, and increasing doses of laromestrocel are associated with decreases in soluble (degraded) tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (TIE2), the cognate receptor for the angiopoietins, identifying a potential biomarker of laromestrocel responsiveness. These findings identify a stem cell therapy approach for the management of patients with hypomobility and other features of aging frailty.

Graphical abstract

Keywords

1. mesenchymal stem cell
2. laromestrocel
3. aging frailty
4. cell therapy
5. TIE2
6. healthspan
7. longevity
8. inflammaging
9. aging

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