English
French
Conditioned medium from horse amniotic membrane-derived multipotent progenitor cells: immunomodulatory activity in vitro and first clinical application in tendon and ligament injuries in vivo.
Abstract: We have recently demonstrated that heterologous transplantation of horse amniotic membrane-derived mesenchymal cells (AMCs) can be useful for cell therapy applications in tendon diseases, and hypothesized that these cells may promote tendon repair via paracrine-acting molecules targeting inflammatory processes. To test this hypothesis, here we examined the immunomodulatory characteristics of AMCs and of their conditioned medium (AMC-CM) in vitro, and studied the potential therapeutic effect of AMC-CM in thirteen different spontaneous horse tendon and ligament injuries in vivo. Our results demonstrate that AMCs are capable of inhibiting peripheral blood mononuclear cell (PBMC) proliferation after allogenic stimulation either when cocultured in cell-to-cell contact, or when the two cell types are physically separated by a transwell membrane, suggesting that soluble factors are implicated in this phenomenon. Our hypothesis is further supported by the demonstration that PBMC proliferation is inhibited by AMC-CM. In our in vivo studies, no significant adverse effects were observed in treated tendons, and clinical and ultrasonographical evaluation did not reveal evidence of inappropriate tissue or tumor formation. Clinical outcomes were favorable and the significantly lower rate (15.38%) of reinjuries observed compared to untreated animals, suggests that treatment with AMC-CM is very efficacious. In conclusion, this study identifies AMC-CM as a novel therapeutic biological cell-free product for treating horse tendon and ligament diseases.
Publication Date: 2013-07-30 PubMed ID: 23795963DOI: 10.1089/scd.2013.0214Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research investigates the potential use of horse amniotic membrane-derived mesenchymal cells (AMCs) for treating tendon and ligament damage. It highlights how these cells and their conditioned medium (AMC-CM) can target inflammatory processes, resulting in improved clinical outcomes and less reinjury rates.
Objective of the Research
- The purpose of the study was to examine the immunomodulatory characteristics of AMCs and their conditioned medium (AMC-CM) in vitro and to explore the therapeutic effect of AMC-CM on horse tendon and ligament injuries in a clinical setting.
Methodology
- Researchers first demonstrated that AMCs can inhibit blood cell proliferation after stimulation, suggesting that soluble factors can potentially contribute to this phenomenon. The evidence was further supported by the inhibitive effect of AMC-CM on blood cell proliferation.
- The study then focused on the therapeutic effect of AMC-CM on spontaneous horse tendon and ligament injuries. Thirteen case studies were observed to ascertain the clinical impact of this treatment.
Findings
- Results showed AMCs’ ability to disrupt the proliferation of certain blood cells, pointing towards the paracrine-function of AMCs.
- The in vivo application of AMC-CM showed no significant negative side-effects and there were no evidence of inappropriate tissue or tumor development on the treated areas, implying that this treatment may be safe to use.
- Favorable clinical outcomes were achieved with a substantially lower reinjury rate (15.38%) as compared to untreated cases, pointing to the efficacy of this treatment.
Conclusion
- The study concluded that AMC-CM represents a promising therapeutic biological cell-free product for treating horse tendon and ligament injuries. It emphasizes the potential of AMC-CM in cell therapy, particularly for tendon and ligament diseases.
Cite This Article
APA
Lange-Consiglio A, Rossi D, Tassan S, Perego R, Cremonesi F, Parolini O.
(2013).
Conditioned medium from horse amniotic membrane-derived multipotent progenitor cells: immunomodulatory activity in vitro and first clinical application in tendon and ligament injuries in vivo.
Stem Cells Dev, 22(22), 3015-3024.
https://doi.org/10.1089/scd.2013.0214 Publication
Researcher Affiliations
- 1 Reproduction Unit, Large Animal Hospital, Universitu00e0 degli Studi di Milano , Lodi, Italy .
MeSH Terms
- Amnion / cytology
- Amnion / immunology
- Amnion / metabolism
- Animals
- Cell Communication
- Cell Differentiation / drug effects
- Cell Proliferation / drug effects
- Cells, Cultured
- Coculture Techniques
- Culture Media, Conditioned / pharmacology
- Female
- Horses
- Immunomodulation
- Leukocytes, Mononuclear / cytology
- Leukocytes, Mononuclear / drug effects
- Leukocytes, Mononuclear / immunology
- Ligaments / drug effects
- Ligaments / immunology
- Ligaments / injuries
- Mesenchymal Stem Cells / cytology
- Mesenchymal Stem Cells / immunology
- Mesenchymal Stem Cells / metabolism
- Multipotent Stem Cells / cytology
- Multipotent Stem Cells / immunology
- Multipotent Stem Cells / metabolism
- Signal Transduction
- Tendon Injuries / drug therapy
- Tendon Injuries / immunology
- Tendons / drug effects
- Tendons / immunology
Citations
This article has been cited 40 times.- Soukup R, Gerner I, Mohr T, Gueltekin S, Grillari J, Jenner F. Mesenchymal Stem Cell Conditioned Medium Modulates Inflammation in Tenocytes: Complete Conditioned Medium Has Superior Therapeutic Efficacy than Its Extracellular Vesicle Fraction.. Int J Mol Sci 2023 Jun 29;24(13).
- Lange-Consiglio A, Gaspari G, Funghi F, Capra E, Cretich M, Frigerio R, Bosi G, Cremonesi F. Amniotic Mesenchymal-Derived Extracellular Vesicles and Their Role in the Prevention of Persistent Post-Breeding Induced Endometritis.. Int J Mol Sci 2023 Mar 8;24(6).
- Ning C, Li P, Gao C, Fu L, Liao Z, Tian G, Yin H, Li M, Sui X, Yuan Z, Liu S, Guo Q. Recent advances in tendon tissue engineering strategy.. Front Bioeng Biotechnol 2023;11:1115312.
- Quintero D, Perucca Orfei C, Kaplan LD, de Girolamo L, Best TM, Kouroupis D. The roles and therapeutic potentialof mesenchymal stem/stromal cells and their extracellular vesicles in tendinopathies.. Front Bioeng Biotechnol 2023;11:1040762.
- Kearney CM, Khatab S, van Buul GM, Plomp SGM, Korthagen NM, Labbertu00e9 MC, Goodrich LR, Kisiday JD, Van Weeren PR, van Osch GJVM, Brama PAJ. Treatment Effects of Intra-Articular Allogenic Mesenchymal Stem Cell Secretome in an Equine Model of Joint Inflammation.. Front Vet Sci 2022;9:907616.
- Russo V, El Khatib M, Prencipe G, Citeroni MR, Faydaver M, Mauro A, Berardinelli P, Cerveru00f3-Varona A, Haidar-Montes AA, Turriani M, Di Giacinto O, Raspa M, Scavizzi F, Bonaventura F, Stu00f6ckl J, Barboni B. Tendon Immune Regeneration: Insights on the Synergetic Role of Stem and Immune Cells during Tendon Regeneration.. Cells 2022 Jan 27;11(3).
- Lakhani A, Sharma E, Kapila A, Khatri K. Known data on applied regenerative medicine in tendon healing.. Bioinformation 2021;17(4):514-527.
- Mocchi M, Grolli S, Dotti S, Di Silvestre D, Villa R, Berni P, Conti V, Passignani G, Brambilla F, Bue MD, Catenacci L, Sorrenti M, Segale L, Bari E, Mauri P, Torre ML, Perteghella S. Equine Mesenchymal Stem/Stromal Cells Freeze-Dried Secretome (Lyosecretome) for the Treatment of Musculoskeletal Diseases: Production Process Validation and Batch Release Test for Clinical Use.. Pharmaceuticals (Basel) 2021 Jun 10;14(6).
- Somal A, Bhat IA, Pandey S, Ansari MM, Indu B, Panda BSK, Bharti MK, Chandra V, Saikumar G, Sharma GT. Comparative analysis of the immunomodulatory potential of caprine fetal adnexa derived mesenchymal stem cells.. Mol Biol Rep 2021 May;48(5):3913-3923.
- Citeroni MR, Mauro A, Ciardulli MC, Di Mattia M, El Khatib M, Russo V, Turriani M, Santer M, Della Porta G, Maffulli N, Forsyth NR, Barboni B. Amnion-Derived Teno-Inductive Secretomes: A Novel Approach to Foster Tendon Differentiation and Regeneration in an Ovine Model.. Front Bioeng Biotechnol 2021;9:649288.
- Villatoro AJ, Martu00edn-Astorga MDC, Alcoholado C, Su00e1nchez-Martu00edn MDM, Becerra J. Proteomic Analysis of the Secretome and Exosomes of Feline Adipose-Derived Mesenchymal Stem Cells.. Animals (Basel) 2021 Jan 24;11(2).
- Ribitsch I, Oreff GL, Jenner F. Regenerative Medicine for Equine Musculoskeletal Diseases.. Animals (Basel) 2021 Jan 19;11(1).
- Citeroni MR, Ciardulli MC, Russo V, Della Porta G, Mauro A, El Khatib M, Di Mattia M, Galesso D, Barbera C, Forsyth NR, Maffulli N, Barboni B. In Vitro Innovation of Tendon Tissue Engineering Strategies.. Int J Mol Sci 2020 Sep 14;21(18).
- Lui PPY. Mesenchymal Stem Cell-Derived Extracellular Vesicles for the Promotion of Tendon Repair - an Update of Literature.. Stem Cell Rev Rep 2021 Apr;17(2):379-389.
- El Khatib M, Mauro A, Wyrwa R, Di Mattia M, Turriani M, Di Giacinto O, Kretzschmar B, Seemann T, Valbonetti L, Berardinelli P, Schnabelrauch M, Barboni B, Russo V. Fabrication and Plasma Surface Activation of Aligned Electrospun PLGA Fiber Fleeces with Improved Adhesion and Infiltration of Amniotic Epithelial Stem Cells Maintaining their Teno-inductive Potential.. Molecules 2020 Jul 11;25(14).
- Lange-Consiglio A, Funghi F, Cantile C, Idda A, Cremonesi F, Riccaboni P. Case Report: Use of Amniotic Microvesicles for Regenerative Medicine Treatment of a Mare With Chronic Endometritis.. Front Vet Sci 2020;7:347.
- Mocchi M, Dotti S, Bue MD, Villa R, Bari E, Perteghella S, Torre ML, Grolli S. Veterinary Regenerative Medicine for Musculoskeletal Disorders: Can Mesenchymal Stem/Stromal Cells and Their Secretome Be the New Frontier?. Cells 2020 Jun 11;9(6).
- El Khatib M, Mauro A, Di Mattia M, Wyrwa R, Schweder M, Ancora M, Lazzaro F, Berardinelli P, Valbonetti L, Di Giacinto O, Polci A, Cammu00e0 C, Schnabelrauch M, Barboni B, Russo V. Electrospun PLGA Fiber Diameter and Alignment of Tendon Biomimetic Fleece Potentiate Tenogenic Differentiation and Immunomodulatory Function of Amniotic Epithelial Stem Cells.. Cells 2020 May 13;9(5).
- Greco L, Russo V, Rapino C, Germanio CD, Fezza F, Bernabu00f2 N, Berardinelli P, Peserico A, Fazio D, Maccarrone M, Mattioli M, Barboni B. Characterization of Endocannabinoid System and Interleukin Profiles in Ovine AEC: Cannabinoid Receptors Type-1 and Type-2 as Key Effectors of Pro-Inflammatory Response.. Cells 2020 Apr 18;9(4).
- Rhatomy S, Prasetyo TE, Setyawan R, Soekarno NR, Romaniyanto F, Sedjati AP, Sumarwoto T, Utomo DN, Suroto H, Mahyudin F, Prakoeswa CRS. Prospect of stem cells conditioned medium (secretome) in ligament and tendon healing: A systematic review.. Stem Cells Transl Med 2020 Aug;9(8):895-902.
- Lange-Consiglio A, Romele P, Magatti M, Silini A, Idda A, Martino NA, Cremonesi F, Parolini O. Priming with inflammatory cytokines is not a prerequisite to increase immune-suppressive effects and responsiveness of equine amniotic mesenchymal stromal cells.. Stem Cell Res Ther 2020 Mar 4;11(1):99.
- Huddleston HP, Cohn MR, Haunschild ED, Wong SE, Farr J, Yanke AB. Amniotic Product Treatments: Clinical and Basic Science Evidence.. Curr Rev Musculoskelet Med 2020 Apr;13(2):148-154.
- Lange-Consiglio A, Gusmara C, Manfredi E, Idda A, Soggiu A, Greco V, Bonizzi L, Cremonesi F, Zecconi A. Antimicrobial Effects of Conditioned Medium From Amniotic Progenitor Cells in vitro and in vivo: Toward Tissue Regenerative Therapies for Bovine Mastitis.. Front Vet Sci 2019;6:443.
- Al Naem M, Bourebaba L, Kucharczyk K, Ru00f6cken M, Marycz K. Therapeutic mesenchymal stromal stem cells: Isolation, characterization and role in equine regenerative medicine and metabolic disorders.. Stem Cell Rev Rep 2020 Apr;16(2):301-322.
- Shojaee A, Parham A. Strategies of tenogenic differentiation of equine stem cells for tendon repair: current status and challenges.. Stem Cell Res Ther 2019 Jun 18;10(1):181.
- Han SW, Kim YY, Kang WJ, Kim HC, Ku SY, Kang BC, Yun JW. The Use of Normal Stem Cells and Cancer Stem Cells for Potential Anti-Cancer Therapeutic Strategy.. Tissue Eng Regen Med 2018 Aug;15(4):365-380.
- Lange-Consiglio A, Lazzari B, Perrini C, Pizzi F, Stella A, Cremonesi F, Capra E. MicroRNAs of Equine Amniotic Mesenchymal Cell-derived Microvesicles and Their Involvement in Anti-inflammatory Processes.. Cell Transplant 2018 Jan;27(1):45-54.
- Cavallini C, Zannini C, Olivi E, Tassinari R, Taglioli V, Rossi M, Poggi P, Chatgilialoglu A, Simonazzi G, Alviano F, Bonsi L, Ventura C. Restoring In Vivo-Like Membrane Lipidomics Promotes Exosome Trophic Behavior from Human Placental Mesenchymal Stromal/Stem Cells.. Cell Transplant 2018 Jan;27(1):55-69.
- Barboni B, Russo V, Berardinelli P, Mauro A, Valbonetti L, Sanyal H, Canciello A, Greco L, Muttini A, Gatta V, Stuppia L, Mattioli M. Placental Stem Cells from Domestic Animals: Translational Potential and Clinical Relevance.. Cell Transplant 2018 Jan;27(1):93-116.
- Silini AR, Magatti M, Cargnoni A, Parolini O. Is Immune Modulation the Mechanism Underlying the Beneficial Effects of Amniotic Cells and Their Derivatives in Regenerative Medicine?. Cell Transplant 2017 Apr 13;26(4):531-539.
- Perrini C, Strillacci MG, Bagnato A, Esposti P, Marini MG, Corradetti B, Bizzaro D, Idda A, Ledda S, Capra E, Pizzi F, Lange-Consiglio A, Cremonesi F. Microvesicles secreted from equine amniotic-derived cells and their potential role in reducing inflammation in endometrial cells in an in-vitro model.. Stem Cell Res Ther 2016 Nov 18;7(1):169.
- Zucca E, Corsini E, Galbiati V, Lange-Consiglio A, Ferrucci F. Evaluation of amniotic mesenchymal cell derivatives on cytokine production in equine alveolar macrophages: an in vitro approach to lung inflammation.. Stem Cell Res Ther 2016 Sep 20;7(1):137.
- Lui PP. Stem cell technology for tendon regeneration: current status, challenges, and future research directions.. Stem Cells Cloning 2015;8:163-74.
- Zomer HD, Vidane AS, Gonu00e7alves NN, Ambru00f3sio CE. Mesenchymal and induced pluripotent stem cells: general insights and clinical perspectives.. Stem Cells Cloning 2015;8:125-34.
- Muttini A, Russo V, Rossi E, Mattioli M, Barboni B, Tosi U, Maffulli N, Valbonetti L, Abate M. Pilot experimental study on amniotic epithelial mesenchymal cell transplantation in natural occurring tendinopathy in horses. Ultrasonographic and histological comparison.. Muscles Ligaments Tendons J 2015 Jan-Mar;5(1):5-11.
- Corradetti B, Correani A, Romaldini A, Marini MG, Bizzaro D, Perrini C, Cremonesi F, Lange-Consiglio A. Amniotic membrane-derived mesenchymal cells and their conditioned media: potential candidates for uterine regenerative therapy in the horse.. PLoS One 2014;9(10):e111324.
- Vidane AS, Souza AF, Sampaio RV, Bressan FF, Pieri NC, Martins DS, Meirelles FV, Miglino MA, Ambru00f3sio CE. Cat amniotic membrane multipotent cells are nontumorigenic and are safe for use in cell transplantation.. Stem Cells Cloning 2014;7:71-8.
- Ku00f6nig J, Weiss G, Rossi D, Wankhammer K, Reinisch A, Kinzer M, Huppertz B, Pfeiffer D, Parolini O, Lang I. Placental mesenchymal stromal cells derived from blood vessels or avascular tissues: what is the better choice to support endothelial cell function?. Stem Cells Dev 2015 Jan 1;24(1):115-31.
- Paterson YZ, Rash N, Garvican ER, Paillot R, Guest DJ. Equine mesenchymal stromal cells and embryo-derived stem cells are immune privileged in vitro.. Stem Cell Res Ther 2014 Jul 30;5(4):90.
- Barboni B, Russo V, Curini V, Martelli A, Berardinelli P, Mauro A, Mattioli M, Marchisio M, Bonassi Signoroni P, Parolini O, Colosimo A. Gestational stage affects amniotic epithelial cells phenotype, methylation status, immunomodulatory and stemness properties.. Stem Cell Rev Rep 2014 Oct;10(5):725-41.
Secure Payments
Satisfaction Guarantee
We offer a 60-day guarantee to ensure you are completely satisfied.
Fast & Free Shipping
We provide fast and free shipping on all orders over $40.