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Trials
Published in: Trials 1/2024

Open Access 01-12-2024 | Cytokines | Research

Safety and efficacy of autologous adipose tissue-derived stem cell transplantation in aging-related low-grade inflammation patients: a single-group, open-label, phase I clinical trial

Authors: Ngoc-Huynh Ton Nguyen, Hao Thanh Phan, Phong Minh Le, Lan-Huong Thi Nguyen, Thuy Thi Do, Thien-Phuc Thanh Phan, Trinh Van Le, Thanh Minh Dang, Chinh-Nhan Lu Phan, Tung-Loan Thi Dang, Nhung Hai Truong

Published in: Trials | Issue 1/2024

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Abstract

Background

Inflamm-aging is associated with the rate of aging and is significantly related to diseases such as Alzheimer’s disease, Parkinson’s disease, atherosclerosis, heart disease, and age-related degenerative diseases such as type II diabetes and osteoporosis. This study aims to evaluate the safety and efficiency of autologous adipose tissue-derived mesenchymal stem cell (AD-MSC) transplantation in aging-related low-grade inflammation patients.

Methods

This study is a single-group, open-label, phase I clinical trial in which patients treated with 2 infusions (100 million cells i.v) of autologous AD-MSCs were initially evaluated in 12 inflamm-aging patients who concurrently had highly proinflammatory cytokines and 2 of the following 3 diseases: diabetes, dyslipidemia, and obesity. The treatment effects were evaluated based on plasma cytokines.

Results

During the study’s follow-up period, no adverse effects were observed in AD-MSC injection patients. Compared to baseline (D-44), the inflammatory cytokines IL-1α, IL-1β, IL-8, IL-6, and TNF-α were significantly reduced after 180 days (D180) of MSC infusion. IL-4/IL-10 at 90 days (D90) and IL-2/IL-10 at D180 increased, reversing the imbalance between proinflammatory and inflammatory ratios in the patients.

Conclusion

AD-MSCs represent a potential intervention to prevent age-related inflammation in patients.

Trial registration

ClinicalTrials.gov number is NCT05827757, first registered on 13th Oct 2020
Appendix
Available only for authorised users
Literature
1.
Franceschi C, Bonafè M, Valensin S, et al. Inflamm-aging: an evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908(1):244–54.PubMedCrossRef
2.
Castellani GC, Menichetti G, Garagnani P, et al. Systems medicine of inflammaging. Brief Bioinform. 2016;17(3):527–40.PubMedCrossRef
3.
Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014;69(Suppl_1):S4–9.PubMedCrossRef
4.
5.
Chen Y, Liu S, Leng SX. Chronic low-grade inflammatory phenotype (CLIP) and senescent immune dysregulation. Clin Ther. 2019;41(3):400–9.PubMedCrossRef
6.
Singh T, Newman AB. Inflammatory markers in population studies of aging. Ageing Res Rev. 2011;10(3):319–29.PubMedCrossRef
7.
Franceschi C, Garagnani P, Vitale G, Capri M, Salvioli S. Inflammaging and ‘Garb-aging.’ Trends Endocrinol Metab. 2017;28(3):199–212.PubMedCrossRef
8.
9.
Prattichizzo F, De Nigris V, Spiga R, et al. Inflammageing and metaflammation: the yin and yang of type 2 diabetes. Ageing Res Rev. 2018;41:1–17.PubMedCrossRef
10.
Lencel P, Magne D. Inflammaging: the driving force in osteoporosis? Med Hypotheses. 2011;76(3):317–21.PubMedCrossRef
11.
Coppé JP, Desprez PY, Krtolica A, Campisi J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol. 2010;5:99–118.PubMedPubMedCentralCrossRef
12.
Panés J, García-Olmo D, Van Assche G, et al. Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn’s disease: a phase 3 randomised, double-blind controlled trial. Lancet (London, England). 2016;388(10051):1281–90.PubMedCrossRef
13.
Mao F, Tu Q, Wang L, et al. Mesenchymal stem cells and their therapeutic applications in inflammatory bowel disease. Oncotarget. 2017;8(23):38008–21.PubMedPubMedCentralCrossRef
14.
Sarsenova M, Issabekova A, Abisheva S, Rutskaya-Moroshan K, Ogay V, Saparov A. Mesenchymal stem cell-based therapy for rheumatoid arthritis. Int J Mol Sci. 2021;22(21):11592.PubMedPubMedCentralCrossRef
15.
Yang Y, He X, Zhao R, et al. Serum IFN-γ levels predict the therapeutic effect of mesenchymal stem cell transplantation in active rheumatoid arthritis. J Transl Med. 2018;16(1):165.PubMedPubMedCentralCrossRef
16.
Wang L, Huang S, Li S, et al. Efficacy and safety of umbilical cord mesenchymal stem cell therapy for rheumatoid arthritis patients: a prospective phase I/II study. Drug Des Dev Ther. 2019;13:4331–40.CrossRef
17.
Wang L, Wang L, Cong X, et al. Human umbilical cord mesenchymal stem cell therapy for patients with active rheumatoid arthritis: safety and efficacy. Stem Cells Dev. 2013;22(24):3192–202.PubMedCrossRef
18.
Alanazi A, Alassiri M, Jawdat D, Almalik Y. Mesenchymal stem cell therapy: a review of clinical trials for multiple sclerosis. Regen Ther. 2022;21:201–9.PubMedPubMedCentralCrossRef
19.
20.
Planat-Benard V, Varin A, Casteilla L. MSCs and inflammatory cells crosstalk in regenerative medicine: concerted actions for optimized resolution driven by energy metabolism. Front Immunol. 2021;12:626755.PubMedPubMedCentralCrossRef
21.
Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315–7.PubMedCrossRef
22.
23.
Neves J, Sousa-Victor P. Regulation of inflammation as an anti-aging intervention. FEBS J. 2020;287(1):43–52.PubMedCrossRef
24.
25.
Arnson Y, Shoenfeld Y, Amital H. Effects of tobacco smoke on immunity, inflammation and autoimmunity. J Autoimmun. 2010;34(3):J258–265.PubMedCrossRef
26.
Wyczalkowska-Tomasik A, Czarkowska-Paczek B, Zielenkiewicz M, Paczek L. Inflammatory markers change with age, but do not fall beyond reported normal ranges. Arch Immunol Ther Exp. 2016;64(3):249–54.CrossRef
27.
Wolf J, Weinberger B, Arnold CR, Maier AB, Westendorp RG, Grubeck-Loebenstein B. The effect of chronological age on the inflammatory response of human fibroblasts. Exp Gerontol. 2012;47(9):749–53.PubMedPubMedCentralCrossRef
28.
29.
Barajas-Gómez BA, Rosas-Carrasco O, Morales-Rosales SL, et al. Relationship of inflammatory profile of elderly patients serum and senescence-associated secretory phenotype with human breast cancer cells proliferation: role of IL6/IL8 ratio. Cytokine. 2017;91:13–29.PubMedCrossRef
30.
Harris TB, Ferrucci L, Tracy RP, et al. Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am J Med. 1999;106(5):506–12.PubMedCrossRef
31.
Krabbe KS, Pedersen M, Bruunsgaard H. Inflammatory mediators in the elderly. Exp Gerontol. 2004;39(5):687–99.PubMedCrossRef
32.
MousaeiGhasroldasht M, Seok J, Park HS, Liakath Ali FB, Al-Hendy A. Stem cell therapy: from idea to clinical practice. Int J Mol Sci. 2022;23(5):2850.CrossRef
33.
Petrus-Reurer S, Romano M, Howlett S, Jones JL, Lombardi G, Saeb-Parsy K. Immunological considerations and challenges for regenerative cellular therapies. Commun Biol. 2021;4(1):798.PubMedPubMedCentralCrossRef
34.
Weiss ARR, Dahlke MH. Immunomodulation by mesenchymal stem cells (MSCs): mechanisms of action of living, apoptotic, and dead MSCs. Front Immunol. 2019;10:1191.PubMedPubMedCentralCrossRef
35.
Liu B, Qu J, Zhang W, Izpisua Belmonte JC, Liu G-H. A stem cell aging framework, from mechanisms to interventions. Cell Rep. 2022;41(3):111451.PubMedCrossRef
36.
37.
Peffers MJ, Collins J, Fang Y, et al. Age-related changes in mesenchymal stem cells identified using a multi-omics approach. Eur Cell Mater. 2016;31:136–59.PubMedCrossRef
38.
Feng G, Zheng K, Cao T, et al. Repeated stimulation by LPS promotes the senescence of DPSCs via TLR4/MyD88-NF-κB-p53/p21 signaling. Cytotechnology. 2018;70(3):1023–35.PubMedPubMedCentralCrossRef
39.
Ringdén O, Uzunel M, Rasmusson I, et al. Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation. 2006;81(10):1390–7.PubMedCrossRef
40.
Németh K, Leelahavanichkul A, Yuen PS, et al. Bone marrow stromal cells attenuate sepsis via prostaglandin E2-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med. 2009;15(1):42–9.PubMedCrossRef
41.
Shi X, Chen Q, Wang F. Mesenchymal stem cells for the treatment of ulcerative colitis: a systematic review and meta-analysis of experimental and clinical studies. Stem Cell Res Ther. 2019;10(1):266.PubMedPubMedCentralCrossRef
Metadata
Title
Safety and efficacy of autologous adipose tissue-derived stem cell transplantation in aging-related low-grade inflammation patients: a single-group, open-label, phase I clinical trial
Authors
Ngoc-Huynh Ton Nguyen
Hao Thanh Phan
Phong Minh Le
Lan-Huong Thi Nguyen
Thuy Thi Do
Thien-Phuc Thanh Phan
Trinh Van Le
Thanh Minh Dang
Chinh-Nhan Lu Phan
Tung-Loan Thi Dang
Nhung Hai Truong
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Trials / Issue 1/2024
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-024-08128-3

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