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Stem cell therapy shows promise for reversing aging-related frailty in new clinical trial
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. Ruiz1,2,17 ∙ Anthony A. Oliva, Jr.3,17 ∙ Kevin N. Ramdas3 ∙ … ∙ Zarin Zainul3 ∙ Brian G. Rash3 ∙ Joshua M. Hare3,16,19 [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
•
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
- mesenchymal stem cell
- laromestrocel
- aging frailty
- cell therapy
- TIE2
- healthspan
- longevity
- inflammaging
- aging
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A rotator cuff tear is an age-related common cause of pain and disability. Studies including our previously published ones have demonstrated that mesenchymal stem cells cultured under hypoxic conditions [hypoxic multipotent stromal cells (MSCs)] facilitate the retention of transplanted cells and promote wound healing. However, there are very few, if any, reports targeting the punctured supraspinatus tendons to create more or equally serous wounds as age-related tears of rotator cuff. It remains to be determined whether transplantation of bone-marrow-derived hypoxic MSCs into the punctured supraspinatus tendon improves tendon repair and, when combined with ultrasound-guided delivery, could be used for future clinical applications. In this study, we used a total of 33 Sprague-Dawley rats in different groups for normal no-punched control, hypoxic MSC treatment, nontreated vehicle control, and MSC preparation, and then evaluated treatment outcomes by biomechanical testing and histological analysis. We found that the ultimate failure load of the hypoxic MSC-treated group was close to that of the normal tendon and significantly greater than that of the nontreated vehicle control group. In vivo tracking of cells labeled with superparamagnetic iron oxide (SPIO) nanoparticles revealed an enhanced retention of transplanted cells at the tear site. Our study demonstrates that hypoxic MSCs improve rotator cuff tear repair in a rat model.
Phase I trial of hES cell-derived dopaminergic neurons for Parkinson’s disease
Parkinson’s disease is a progressive neurodegenerative condition with a considerable health and economic burden1. It is characterized by the loss of midbrain dopaminergic neurons and a diminished response to symptomatic medical or surgical therapy as the disease progresses. Cell therapy aims to replenish lost dopaminergic neurons and their striatal projections by intrastriatal grafting. Here, we report the results of an open-label phase I clinical trial (NCT04802733) of an investigational cryopreserved, off-the-shelf dopaminergic neuron progenitor cell product (bemdaneprocel) derived from human embryonic stem (hES) cells and grafted bilaterally into the putamen of patients with Parkinson’s disease. Twelve patients were enrolled sequentially in two cohorts—a low-dose (0.9 million cells, n = 5) and a high-dose (2.7 million cells, n = 7) cohort—and all of the participants received one year of immunosuppression. The trial achieved its primary objectives of safety and tolerability one year after transplantation, with no adverse events related to the cell product. At 18 months after grafting, putaminal 18Fluoro-DOPA positron emission tomography uptake increased, indicating graft survival. Secondary and exploratory clinical outcomes showed improvement or stability, including improvement in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III OFF scores by an average of 23 points in the high-dose cohort. There were no graft-induced dyskinesias. These data demonstrate safety and support future definitive clinical studies.
Repeated Intravenous Administration of Mesenchymal Stromal Cells Produces Cumulative Beneficial Effects in Chronic Ischemic Cardiomyopathy
Cell therapy is a potentially useful approach to treating heart failure (HF) secondary to chronic ischemic cardiomyopathy (ischemic HF). Despite controversy, the preclinical data in the field of cell therapy are clear: Although transplanted cells do not regenerate cardiomyocytes, preclinical studies have consistently shown that they improve cardiac performance. Bone marrow–derived mesenchymal stromal cells (MSCs) are among the most promising cell types in the preclinical arena1 and for patients with ischemic HF.
The field of cell therapy is evolving rapidly. The fundamental shift has been the recognition that all cell types fail to engraft in the heart and instead work via paracrine mechanisms. This concept has 2 corollaries: (1) because transplanted cells do not persist in the heart for more than a few weeks, giving repeated doses seems logical; and (2) because cells work by releasing factors in the environment, intravenous (IV) therapy may also be effective by enabling systemic release of these factors.