Clinical and Translational ReportVolume 33, Issue 3p393-404.e4March 05, 2026

Download Full Issue

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 jhare@longeveron.com … 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

• Get Access
• Cite
• Share
• Set Alert
• Get Rights
• Reprints

Download Full Issue

Previous articleNext article

Show Outline

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

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

Get full text access

Log in, subscribe or purchase for full access.

Get Access

References

1.

Hoogendijk, E.O. ∙ Afilalo, J. ∙ Ensrud, K.E. …

Frailty: implications for clinical practice and public health

Lancet. 2019; 394:1365-1375

Google Scholar

2.

Kim, D.H. ∙ Rockwood, K.

Frailty in Older Adults

N. Engl. J. Med. 2024; 391:538-548

Google Scholar

3.

Suo, X. ∙ Li, L. ∙ Guo, J. …

Association of Frailty With Dementia and the Mediating Role of Brain Structure and Immunometabolic Signatures

Neurology. 2025; 105, e214199

Google Scholar

4.

O’Caoimh, R. ∙ Sezgin, D. ∙ O’Donovan, M.R. …

Prevalence of frailty in 62 countries across the world: a systematic review and meta-analysis of population-level studies

Age Ageing. 2021; 50:96-104

Google Scholar

5.

Howlett, S.E. ∙ Rutenberg, A.D. ∙ Rockwood, K.

The degree of frailty as a translational measure of health in aging

Nat. Aging. 2021; 1:651-665

Google Scholar

6.

Boyle, P.A. ∙ Buchman, A.S. ∙ Barnes, L.L. …

Association between life space and risk of mortality in advanced age

J. Am. Geriatr. Soc. 2010; 58:1925-1930

Google Scholar

7.

Xue, Q.L. ∙ Fried, L.P. ∙ Glass, T.A. …

Life-space constriction, development of frailty, and the competing risk of mortality: the Women’s Health And Aging Study I

Am. J. Epidemiol. 2008; 167:240-248

Google Scholar

8.

May, D. ∙ Nayak, U.S. ∙ Isaacs, B.

The life-space diary: a measure of mobility in old people at home

Int. Rehabil. Med. 1985; 7:182-186

Google Scholar

9.

Cohen, H.J. ∙ Smith, D. ∙ Sun, C.L. …

Frailty as determined by a comprehensive geriatric assessment-derived deficit-accumulation index in older patients with cancer who receive chemotherapy

Cancer. 2016; 122:3865-3872

Google Scholar

10.

Mümken, S.A. ∙ Alonso-Perez, E. ∙ Haeger, C. …

Prevention of frailty in relation with social out-of-home activities in older adults: results from the Survey of Health, Ageing, and Retirement in Europe

Eur. J. Ageing. 2024; 21, 35

Google Scholar

11.

Ankuda, C.K. ∙ Freedman, V.A. ∙ Covinsky, K.E. …

Population-Based Screening for Functional Disability in Older Adults

Innov. Aging. 2021; 5, igaa065

Google Scholar

12.

Boxer, R. ∙ Kleppinger, A. ∙ Ahmad, A. …

The 6-minute walk is associated with frailty and predicts mortality in older adults with heart failure

Congest. Heart Fail. 2010; 16:208-213

Google Scholar

13.

Harada, N.D. ∙ Chiu, V. ∙ Stewart, A.L.

Mobility-related function in older adults: assessment with a 6-minute walk test

Arch. Phys. Med. Rehabil. 1999; 80:837-841

Google Scholar

14.

Walston, J. ∙ Bandeen-Roche, K. ∙ Buta, B. …

Moving Frailty Toward Clinical Practice: NIA Intramural Frailty Science Symposium Summary

J. Am. Geriatr. Soc. 2019; 67:1559-1564

Google Scholar

15.

Bisset, E.S. ∙ Howlett, S.E.

The biology of frailty in humans and animals: Understanding frailty and promoting translation

Aging Med. (Milton). 2019; 2:27-34

Google Scholar

16.

Franceschi, C. ∙ Campisi, J.

Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases

J. Gerontol. A Biol. Sci. Med. Sci. 2014; 69:S4-S9

Google Scholar

17.

Ferrucci, L. ∙ Fabbri, E.

Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty

Nat. Rev. Cardiol. 2018; 15:505-522

Google Scholar

18.

Li, X. ∙ Li, C. ∙ Zhang, W. …

Inflammation and aging: signaling pathways and intervention therapies

Signal Transduct. Target. Ther. 2023; 8:239

Google Scholar

19.

Franceschi, C. ∙ Garagnani, P. ∙ Parini, P. …

Inflammaging: a new immune-metabolic viewpoint for age-related diseases

Nat. Rev. Endocrinol. 2018; 14:576-590

Google Scholar

20.

Damluji, A.A. ∙ Chung, S.E. ∙ Xue, Q.L. …

Frailty and cardiovascular outcomes in the National Health and Aging Trends Study

Eur. Heart J. 2021; 42:3856-3865

Google Scholar

21.

Buch, A. ∙ Carmeli, E. ∙ Boker, L.K. …

Muscle function and fat content in relation to sarcopenia, obesity and frailty of old age–An overview

Exp. Gerontol. 2016; 76:25-32

Google Scholar

22.

Liu, L. ∙ Rando, T.A.

Manifestations and mechanisms of stem cell aging

J. Cell Biol. 2011; 193:257-266

Google Scholar

23.

Matteini, F. ∙ Montserrat-Vazquez, S. ∙ Florian, M.C.

Rejuvenating aged stem cells: therapeutic strategies to extend health and lifespan

FEBS Lett. 2024; 598:2776-2787

Google Scholar

24.

Ferrón, S. ∙ Mira, H. ∙ Franco, S. …

Telomere shortening and chromosomal instability abrogates proliferation of adult but not embryonic neural stem cells

Development. 2004; 131:4059-4070

Google Scholar

25.

Cai, Y. ∙ Xiong, M. ∙ Xin, Z. …

Decoding aging-dependent regenerative decline across tissues at single-cell resolution

Cell Stem Cell. 2023; 30:1674-1691.e8

Google Scholar

26.

Chambers, S.M. ∙ Shaw, C.A. ∙ Gatza, C. …

Aging hematopoietic stem cells decline in function and exhibit epigenetic dysregulation

PLOS Biol. 2007; 5, e201

Google Scholar

27.

Pittenger, M.F. ∙ Discher, D.E. ∙ Péault, B.M. …

Mesenchymal stem cell perspective: cell biology to clinical progress

NPJ Regen. Med. 2019; 4, 22

Google Scholar

28.

Oliva, A.A. ∙ McClain-Moss, L. ∙ Pena, A. …

Allogeneic mesenchymal stem cell therapy: A regenerative medicine approach to geroscience

Aging Med. (Milton). 2019; 2:142-146

Google Scholar

29.

Thompson, M. ∙ Mei, S.H.J. ∙ Wolfe, D. …

Cell therapy with intravascular administration of mesenchymal stromal cells continues to appear safe: An updated systematic review and meta-analysis

EClinicalmedicine. 2020; 19, 100249

Google Scholar

30.

Hare, J.M. ∙ Traverse, J.H. ∙ Henry, T.D. …

A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction

J. Am. Coll. Cardiol. 2009; 54:2277-2286

Google Scholar

31.

Golpanian, S. ∙ El-Khorazaty, J. ∙ Mendizabal, A. …

Effect of aging on human mesenchymal stem cell therapy in ischemic cardiomyopathy patients

J. Am. Coll. Cardiol. 2015; 65:125-132

Google Scholar

32.

Golpanian, S. ∙ DiFede, D.L. ∙ Khan, A. …

Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty

J. Gerontol. A Biol. Sci. Med. Sci. 2017; 72:1505-1512

Google Scholar

33.

Tompkins, B.A. ∙ DiFede, D.L. ∙ Khan, A. …

Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial

J. Gerontol. A Biol. Sci. Med. Sci. 2017; 72:1513-1522

Google Scholar

34.

Golpanian, S. ∙ DiFede, D.L. ∙ Pujol, M.V. …

Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: A phase I/II, randomized, blinded and placebo controlled trial to evaluate the safety and potential efficacy of allogeneic human mesenchymal stem cell infusion in patients with aging frailty

Oncotarget. 2016; 7:11899-11912

Google Scholar

35.

Rash, B.G. ∙ Ramdas, K.N. ∙ Agafonova, N. …

Allogeneic mesenchymal stem cell therapy with laromestrocel in mild Alzheimer’s disease: a randomized controlled phase 2a trial

Nat. Med. 2025; 31:1257-1266

Google Scholar

36.

Brody, M. ∙ Agronin, M. ∙ Herskowitz, B.J. …

Results and insights from a phase I clinical trial of Lomecel-B for Alzheimer’s disease

Alzheimers Dement. 2023; 19:261-273

Google Scholar

37.

Yousefi, K. ∙ Ramdas, K.N. ∙ Ruiz, J.G. …

The Design and Rationale of a Phase 2b, Randomized, Double-Blinded, and Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Lomecel-B in Older Adults with Frailty

J. Frailty Aging. 2022; 11:214-223

Google Scholar

38.

Yuan, H.T. ∙ Khankin, E.V. ∙ Karumanchi, S.A. …

Angiopoietin 2 is a partial agonist/antagonist of Tie2 signaling in the endothelium

Mol. Cell. Biol. 2009; 29:2011-2022

Google Scholar

39.

Fiedler, U. ∙ Reiss, Y. ∙ Scharpfenecker, M. …

Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation

Nat. Med. 2006; 12:235-239

Google Scholar

40.

Fiedler, U. ∙ Krissl, T. ∙ Koidl, S. …

Angiopoietin-1 and angiopoietin-2 share the same binding domains in the Tie-2 receptor involving the first Ig-like loop and the epidermal growth factor-like repeats

J. Biol. Chem. 2003; 278:1721-1727

Google Scholar

41.

Idowu, T.O. ∙ Etzrodt, V. ∙ Seeliger, B. …

Identification of specific Tie2 cleavage sites and therapeutic modulation in experimental sepsis

eLife. 2020; 9, e59520

Google Scholar

42.

Findley, C.M. ∙ Mitchell, R.G. ∙ Duscha, B.D. …

Plasma levels of soluble Tie2 and vascular endothelial growth factor distinguish critical limb ischemia from intermittent claudication in patients with peripheral arterial disease

J. Am. Coll. Cardiol. 2008; 52:387-393

Google Scholar

43.

Lee, K.W. ∙ Lip, G.Y.H. ∙ Blann, A.D.

Plasma angiopoietin-1, angiopoietin-2, angiopoietin receptor tie-2, and vascular endothelial growth factor levels in acute coronary syndromes

Circulation. 2004; 110:2355-2360

Google Scholar

44.

Parikh, S.M.

Targeting Tie2 and the host vascular response in sepsis

Sci. Transl. Med. 2016; 8, 8

Google Scholar

45.

Han, S. ∙ Lee, S.J. ∙ Kim, K.E. …

Amelioration of sepsis by TIE2 activation-induced vascular protection

Sci. Transl. Med. 2016; 8, 335ra55

Google Scholar

46.

Jiang, L. ∙ Hu, X. ∙ Feng, Y. …

Reduction of renal interstitial fibrosis by targeting Tie2 in vascular endothelial cells

Pediatr. Res. 2024; 95:959-965

Google Scholar

47.

Yan, F. ∙ Meng, X. ∙ Cheng, X. …

Potential role between inflammatory cytokines and Tie-2 receptor levels and clinical symptoms in patients with first-episode schizophrenia

BMC Psychiatry. 2023; 23, 538

Google Scholar

48.

Scheufler, K.M. ∙ Drevs, J. ∙ van Velthoven, V. …

Implications of vascular endothelial growth factor, sFlt-1, and sTie-2 in plasma, serum and cerebrospinal fluid during cerebral ischemia in man

J. Cereb. Blood Flow Metab. 2003; 23:99-110

Google Scholar

49.

Shoemaker, M.J. ∙ Curtis, A.B. ∙ Vangsnes, E. …

Clinically meaningful change estimates for the six-minute walk test and daily activity in individuals with chronic heart failure

Cardiopulm. Phys. Ther. J. 2013; 24:21-29

Google Scholar

50.

Kwok, B.C. ∙ Pua, Y.H. ∙ Mamun, K. …

The minimal clinically important difference of six-minute walk in Asian older adults

BMC Geriatr. 2013; 13, 23

Google Scholar

51.

Perera, S. ∙ Mody, S.H. ∙ Woodman, R.C. …

Meaningful change and responsiveness in common physical performance measures in older adults

J. Am. Geriatr. Soc. 2006; 54:743-749

Google Scholar

52.

Yazdanyar, A. ∙ Aziz, M.M. ∙ Enright, P.L. …

Association Between 6-Minute Walk Test and All-Cause Mortality, Coronary Heart Disease-Specific Mortality, and Incident Coronary Heart Disease

J. Aging Health. 2014; 26:583-599

Google Scholar

53.

Bohannon, R.W. ∙ Crouch, R.

Minimal clinically important difference for change in 6-minute walk test distance of adults with pathology: a systematic review

J. Eval. Clin. Pract. 2017; 23:377-381

Google Scholar

54.

Rockwood, K. ∙ Song, X. ∙ MacKnight, C. …

A global clinical measure of fitness and frailty in elderly people

CMAJ. 2005; 173:489-495

Google Scholar

55.

Sack, K.D. ∙ Kellum, J.A. ∙ Parikh, S.M.

The Angiopoietin-Tie2 Pathway in Critical Illness

Crit. Care Clin. 2020; 36:201-216

Google Scholar

56.

Lozito, T.P. ∙ Jackson, W.M. ∙ Nesti, L.J. …

Human mesenchymal stem cells generate a distinct pericellular zone of MMP activities via binding of MMPs and secretion of high levels of TIMPs

Matrix Biol. 2014; 34:132-143

Google Scholar

57.

Elliott, M.R. ∙ Koster, K.M. ∙ Murphy, P.S.

Efferocytosis Signaling in the Regulation of Macrophage Inflammatory Responses

J. Immunol. 2017; 198:1387-1394

Google Scholar

58.

Cheung, T.S. ∙ Giacomini, C. ∙ Cereda, M. …

Apoptosis in mesenchymal stromal cells activates an immunosuppressive secretome predicting clinical response in Crohn’s disease

Mol. Ther. 2023; 31:3531-3544

Google Scholar

59.

Galleu, A. ∙ Riffo-Vasquez, Y. ∙ Trento, C. …

Apoptosis in mesenchymal stromal cells induces in vivo recipient-mediated immunomodulation

Sci. Transl. Med. 2017; 9, eaam7828

Google Scholar

60.

Rockwood, K. ∙ Mitnitski, A.

Frailty defined by deficit accumulation and geriatric medicine defined by frailty

Clin. Geriatr. Med. 2011; 27:17-26

Google Scholar

61.

Juma, S. ∙ Taabazuing, M.M. ∙ Montero-Odasso, M.

Clinical Frailty Scale in an Acute Medicine Unit: a Simple Tool That Predicts Length of Stay

Can. Geriatr. J. 2016; 19:34-39

Google Scholar

62.

Ritt, M. ∙ Ritt, J.I. ∙ Sieber, C.C. …

Comparing the predictive accuracy of frailty, comorbidity, and disability for mortality: a 1-year follow-up in patients hospitalized in geriatric wards

Clin. Interv. Aging. 2017; 12:293-304

Google Scholar

63.

Cesari, M. ∙ Bernabei, R. ∙ Vellas, B. …

Challenges in the Development of Drugs for Sarcopenia and Frailty – Report from the International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force

J. Frailty Aging. 2022; 11:135-142

Google Scholar

64.

Egorin, M.J. ∙ Rosen, D.M. ∙ Sridhara, R. …

Plasma concentrations and pharmacokinetics of dimethylsulfoxide and its metabolites in patients undergoing peripheral-blood stem-cell transplants

J. Clin. Oncol. 1998; 16:610-615

Google Scholar

65.

Cella, D. ∙ Yount, S. ∙ Rothrock, N. …

The Patient-Reported Outcomes Measurement Information System (PROMIS): progress of an NIH Roadmap cooperative group during its first two years

Med. Care. 2007; 45:S3-S11

Google Scholar

66.

Born, J. ∙ Lange, T. ∙ Hansen, K. …

Effects of sleep and circadian rhythm on human circulating immune cells

J. Immunol. 1997; 158:4454-4464

Google Scholar

67.

Bretz, F. ∙ Pinheiro, J.C. ∙ Branson, M.

Combining multiple comparisons and modeling techniques in dose-response studies

Biometrics. 2005; 61:738-748

Google Scholar

68.

Menon, S.M. ∙ Zink, R.C.

Modern Approaches to Clinical Trials Using SAS: Classical, Adaptive, and Bayesian Methods.SAS Institute, 2015

Google Scholar

Figures (5)Figure Viewer

Show all figures

Article metrics

• 1

Citations

• 5

Mentions

View detailsopens in a new tab

Supplemental information (2)

Download all

PDF (820.26 KB)

Document S1. Figures S1 and S2 and Tables S1–S8

PDF (10.91 MB)

Document S2. Article plus supplemental information

Related articles (40)

• Phase 1 dose-escalation trial of sub-endometrial injection of human embryonic stem cells-derived immunity-and-matrix-regulatory cells to promote endometrial angiogenesis in refractory intrauterine adhesion
  • Li et al.

Molecular TherapySeptember 22, 2025

• The safety and tolerability of a one strength dose-escalation scheme for subcutaneous immunotherapy with a native house dust mite extract in Chinese children: A multicenter, randomized, open label clinical trial
  • Zhi et al.

HeliyonApril 10, 2024

• Phase I Escalating-Dose Trial of CAR-T Therapy Targeting CEA+ Metastatic Colorectal Cancers
  • Zhang et al.

Molecular TherapyMarch 18, 2017

Show more

View full text

The post Stem cell therapy shows promise for reversing aging-related frailty in new clinical trial appeared first on Relief Medical Group.

Stem cell therapy has emerged as a groundbreaking treatment approach, particularly for type 1 diabetes, where the autoimmune destruction of beta cells necessitates regenerative strategies to restore insulin production. This article focuses on the recent medical milestone in which autologous stem cell therapy led to insulin independence in a type 1 diabetes patient. This article explores the role of stem cell therapy in reversing diabetes, focusing on the recent medical milestone in which stem cell therapy successfully reversed diabetes in a patient. Stem cells, particularly induced pluripotent stem cells, are used to regenerate pancreatic cells that produce insulin, thereby potentially eliminating the need for insulin injections. The study highlights both the promises and challenges of using stem cell therapy for diabetes including concerns about durability of the response, safety and long-term functionality of generated beta cells. Clinical trials and the ethical considerations of using stem cells are also discussed, along with future directions for stem cell-based diabetes therapies.

Link to Full article

The post First-ever stem cell therapy restores insulin independence in type 1 diabetes: A medical milestone appeared first on Relief Medical Group.

Chinese medical experts have created an ultra-efficient stem cell approach to Parkinson’s disease, raising prospects for treatment for a condition for which there is no known cure.

Parkinson’s disease is often referred to as a “movement disorder”. Its symptoms are caused by the brain failing to generate enough dopamine, due to the death or impairment of the neurons responsible for producing the chemical.

While researchers around the world are exploring stem cell therapies to replenish lost dopaminergic neurons, the team of neurology specialist Shi Jiong at the First Affiliated Hospital of the University of Science and Technology of China (USTC) in Hefei is leading the way.

The post Chinese scientists develop promising stem cell therapy for Parkinson’s disease appeared first on Relief Medical Group.

Objectives: To evaluate the efficacy of repeated intravenous doses of 10   106/kg allo-hMSCs in improving motor symptoms in patients with PD (PwP). Methods: In this phase 2, randomized, placebo-controlled trial (November 2020–July 2023), mild-to-moderate PwP received either three allo-hMSC infusions, one placebo followed by two allo-hMSC infusions, or three placebo infusions at 18-week intervals. Follow-up lasted 88 weeks. The primary outcome was a >70%posterior probability (PP) of a difference in the proportion of participants with ≥5-point improvement in OFF-medication Movement Disorder Society Sponsored Revision of the Unified Parkinson’s Disease Rating Scale-Part III (MDS-UPDRS-III) at week 62. Bayesian analysis was conducted using R v4.2.0.

Results: Forty-five PwP were enrolled. A larger proportion of subjects achieved a ≥5-point improvement in MDS-UPDRS-III in the three-infusion arm compared with placebo at week 62 (mean difference [MD]: 5.0%, PP = 93.7%), translating to a 16.9-point improvement in MDS-UPDRS-III in the three-infusion arm compared with a 14.6-point improvement in the placebo arm. Conversely, fewer subjects in the two-infusion arm compared with placebo showed ≥5-point improvement at week 62 (MD: –62.4%, PP ≥ 99.9%), translating to only a 3.9-point improvement in MDS-UPDRS-III in the two-infusion arm. However, improvement in MDS-UPDRS-III was seen across all treatment arms. Adverse events were mild and transient.

Conclusions: Three infusions of 10   106 allo-hMSCs/kg improved motor function in mild-to-moderate PwP, while two infusions showed less improvement than placebo. To address this discrepancy, future studies should conduct functional potency assays to understand batch-to-batch variability affecting clinical efficacy.

Download the full study here

The post Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells for Parkinson’s Disease: A Randomized Trial appeared first on Relief Medical Group.

The post Advances in Stem Cell Therapies for Rotator Cuff Injuries appeared first on Relief Medical Group.

Tendon-bone insertion injuries such as rotator cuff and anterior cruciate ligament injuries are currently highly common and severe. The key method of treating this kind of injury is the reconstruction operation. The success of this reconstructive process depends on the ability of the graft to incorporate into the bone. Recently, there has been substantial discussion about how to enhance the integration of tendon and bone through biological methods. Stem cells like bone marrow mesenchymal stem cells (MSCs), tendon stem/progenitor cells, synovium-derived MSCs, adipose-derived stem cells, or periosteum-derived periosteal stem cells can self-regenerate and potentially differentiate into different cell types, which have been widely used in tissue repair and regeneration. Thus, we concentrate in this review on the current circumstances of tendon-bone healing using stem cell therapy.

The post Stem cell therapies in tendon-bone healing appeared first on Relief Medical Group.

Despite relatively good results of current symptomatictreatments for rotator cuff disease, there has been an unmetneed for fundamental treatments to halt or reverse the progressof disease. The purpose of this study was to assess the safety andefficacy of intratendinous injection of autologous adiposetissue-derived mesenchymal stem cells (AD MSCs) in patientswith rotator cuff disease. The first part of the study consists ofthree dose-escalation cohorts; the low- (1.0 × 10 cells), mid- (5.0× 10), and high-dose (1.0 × 10) groups with three patients eachfor the evaluation of the safety and tolerability. The second partincluded nine patients receiving the high-dose for theevaluation of the exploratory efficacy. The primary outcomeswere the safety and the shoulder pain and disability index(SPADI). Secondary outcomes included clinical, radiological, andarthroscopic evaluations. Twenty patients were enrolled in thestudy, and two patients were excluded. Intratendinous injectionof AD MSCs was not associated with adverse events. Itsignificantly decreased the SPADI scores by 80% and 77% in themid- and high-dose groups, respectively. Shoulder pain wassignificantly alleviated by 71% in the high-dose group. Magneticresonance imaging examination showed that volume of thebursal-side defect significantly decreased by 90% in the high-dose group. Arthroscopic examination demonstrated thatvolume of the articular- and bursal-side defects decreased by83% and 90% in the mid- and high-dose groups, respectively.Intratendinous injection of autologous AD MSCs in patient witha partial-thickness rotator cuff tear did not cause adverse events,but improved shoulder function, and relieved pain throughregeneration of rotator cuff tendon.

The post Intratendinous Injection of AutologousAdipose Tissue-Derived MesenchymalStem Cells for the Treatment of RotatorCuff Disease: A First-In-Human Trial  appeared first on Relief Medical Group.

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.

The post Mesenchymal Stem Cells From a Hypoxic Culture Can Improve Rotator Cuff Tear Repair appeared first on Relief Medical Group.