The Contribution of Adipose Tissue-Derived Mesenchymal Stem Cells and Platelet-Rich Plasma to the Treatment of Chronic Equine Laminitis: A Proof of Concept.
Abstract: Laminitis, a highly debilitating disease of the foot in ungulates, is characterized by pathological changes of the complex lamellar structures that maintain the appendicular skeleton within the hoof. Laminitis is a multifactorial disease that involves perturbation of the vascular, hematological, and inflammatory homeostasis of the foot. Interestingly, the pathogenesis of the disease resembles what is observed in metabolic syndromes and sepsis-induced organ failure in humans and animals. We hypothesized that local administration of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) might contribute to establishing an anti-inflammatory and pro-angiogenic environment, and could stimulate the injured tissue in order to restore its functional integrity. According to this assumption, an experimental protocol based on the local intravenous administration of adipose tissue-derived MSCs (aMSCs) in combination with PRP was developed for the treatment of horses affected by chronic laminitis. Nine horses with severely compromised venograms (showing grade III and IV laminitis) that had been unsuccessfully treated with conventional therapies were enrolled. aMSCs and PRP (15 × 10⁶ cells resuspended in 15 mL of PRP) were injected into the lateral or medial digital vein three times, at one-month intervals. The first administration was performed with allogeneic aMSCs, while for the following administrations, autologous aMSCs were used. There was no adverse short-term reaction to the intravenous injection of aMSCs. In the long term, venograms outlined, in all subjects, a progressive amelioration of the vascularization of the foot. An improvement in the structure and function of the hoof was also observed. No adverse events were reported during the follow-up, and the horses returned to a comfortable quality of life. Although the number of animals enrolled in the study is limited, both clinical observations and venography demonstrated an enhancement in the condition of all horses, suggesting that the regenerative therapies in chronic laminitis could be useful, and are worthy of further investigation.
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This study explores how a treatment involving adipose tissue-derived mesenchymal stem cells (aMSCs) and platelet-rich plasma (PRP) can improve chronic laminitis, a serious foot disease in horses. Nine horses with advanced laminitis were treated over three months using this protocol, resulting in improved foot health and quality of life.
Deeper Understanding of the Research Paper
The paper presents an investigation into treating chronic laminitis, a debilitating disease affecting the feet of hoofed animals, in particular, horses. The disease is complex, involving the subversion of regular vascular, hematological, and inflammatory systems within the foot. This condition mirrors sepsis-induced organ failure and metabolic syndromes found in humans and other animals.
The research is based on the hypothesis that local delivery of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) could create an anti-inflammatory and pro-angiogenic environment, potentially stimulating tissue repair and recovery. The researchers propose a treatment protocol involving intravenous administration of adipose tissue-derived MSCs (aMSCs) in conjunction with PRP for horses suffering from chronic laminitis.
Methodology and Results
The study involved nine horses diagnosed with severe laminitis (grade III and IV) that hadn’t responded to traditional therapies. These horses underwent a treatment involving both aMSCs and PRP injections, segmented over three one-month intervals.
The first injection contained allogeneic (donor) aMSCs due to the time required to grow autologous (patient’s own) aMSCs, and the following injections were comprised of autologous aMSCs. All injections contained 15×10⁶ cells resuspended in 15ml of PRP.
The horses showed no short-term adverse reactions to the aMSCs injections. Long-term observation revealed a positive progression in foot vascularization and overall hoof structure/function. During the study and subsequent follow-up, the horses appeared to return to a high quality of life with no negative side effects reported.
Conclusion
Although there is a cautionary note that the sample size of the study was small, the alleviation of the condition in all the horses included strongly suggests that this treatment protocol shows promise. The researchers call for continued investigation into the benefits of such regenerative therapies in managing chronic laminitis in horses.
Cite This Article
APA
Angelone M, Conti V, Biacca C, Battaglia B, Pecorari L, Piana F, Gnudi G, Leonardi F, Ramoni R, Basini G, Dotti S, Renzi S, Ferrari M, Grolli S.
(2017).
The Contribution of Adipose Tissue-Derived Mesenchymal Stem Cells and Platelet-Rich Plasma to the Treatment of Chronic Equine Laminitis: A Proof of Concept.
Int J Mol Sci, 18(10).
https://doi.org/10.3390/ijms18102122
Dipartimento Scienze Mediche Veterinarie, Università di Parma, Via del taglio, 10, 43126 Parma, Italy. marioangelonevet@libero.it.
Conti, Virna
Dipartimento Scienze Mediche Veterinarie, Università di Parma, Via del taglio, 10, 43126 Parma, Italy. virna.conti@unipr.it.
Biacca, Cristiano
Veterinary Practitioner, Dipartimento Scienze Mediche Veterinarie, Università di Parma, Via del taglio, 10, 43126 Parma, Italy. cristiano.biacca@libero.it.
Battaglia, Beatrice
Veterinary Practitioner, Dipartimento Scienze Mediche Veterinarie, Università di Parma, Via del taglio, 10, 43126 Parma, Italy. beatricechiarabattaglia@gmail.com.it.
Pecorari, Laura
Veterinary Practitioner, Dipartimento Scienze Mediche Veterinarie, Università di Parma, Via del taglio, 10, 43126 Parma, Italy. laurapecorari.dvm@gmail.com.
Piana, Francesco
Veterinary Practitioner, Dipartimento Scienze Mediche Veterinarie, Università di Parma, Via del taglio, 10, 43126 Parma, Italy. f.piana.vet@gmail.com.
Gnudi, Giacomo
Dipartimento Scienze Mediche Veterinarie, Università di Parma, Via del taglio, 10, 43126 Parma, Italy. giacomo.gnudi@unipr.it.
Leonardi, Fabio
Dipartimento Scienze Mediche Veterinarie, Università di Parma, Via del taglio, 10, 43126 Parma, Italy. fabio.leonardi@unipr.it.
Ramoni, Roberto
Dipartimento Scienze Mediche Veterinarie, Università di Parma, Via del taglio, 10, 43126 Parma, Italy. roberto.ramoni@unipr.it.
Basini, Giuseppina
Dipartimento Scienze Mediche Veterinarie, Università di Parma, Via del taglio, 10, 43126 Parma, Italy. giuseppina.basini@unipr.it.
Dotti, Silvia
Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna, Via Bianchi 9, 25124 Brescia, Italy. silvia.dotti@izsler.it.
Renzi, Sabrina
Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna, Via Bianchi 9, 25124 Brescia, Italy. sabrina.renzi@izsler.it.
Ferrari, Maura
Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna, Via Bianchi 9, 25124 Brescia, Italy. maura1.ferrari@libero.it.
Grolli, Stefano
Dipartimento Scienze Mediche Veterinarie, Università di Parma, Via del taglio, 10, 43126 Parma, Italy. stefano.grolli@unipr.it.
Pollitt C., Collins S.N.. Chronic laminitis.. In: Ross M.W., Dyson S.J., editors. Diagnosis and Management of Lameness in the Horse. 2nd ed. Elsevier Saunders Health Sciences; St. Louis, MO, USA: 2010. pp. 374–377.
Pollitt C.. Pathophysiology of laminitis.. In: Ross M.W., Dyson S.J., editors. Diagnosis and Management of Lameness in the Horse. 2nd ed. Elsevier Saunders Health Sciences; St. Louis, MO, USA: 2010. pp. 366–371.
Belknap J.K., Faleiros R., Black S.J., Johnson P.J., Eades S.. The laminar leukocyte: From sepsis to endocrinopathic models of laminitis.. J. Vet. Sci. 2011;31:584–585.
Monsel A., Zhu Y.G., Gennai S., Hao Q., Liu J., Lee J.W.. Cell-based therapy for acute organ injury: Preclinical evidence and ongoing clinical trials using mesenchymal stem cells.. Anesthesiology 2014;121:1099–1121.
Matthay M.A., Pati S., Lee J.W.. Concise Review: Mesenchymal Stem (Stromal) Cells: Biology and Preclinical Evidence for Therapeutic Potential for Organ Dysfunction Following Trauma or Sepsis.. Stem Cells 2017;35:316–324.
Inan M., Bakar E., Cerkezkayabekir A., Sanal F., Ulucam E., Subaşı C., Karaöz E.. Mesenchymal stem cells increase antioxidant capacity in intestinal ischemia/reperfusion damage.. J. Pediatr. Surg. 2017;52:1196–1206.
Block G.J., Ohkouchi S., Fung F., Frenkel J., Gregory C., Pochampally R., DiMattia G., Sullivan D.E., Prockop D.J.. Multipotent stromal cells (MSCs) are activated to reduce apoptosis in part by upregulation and secretion of stanniocalcin-1 (STC-1). Stem Cells 2009;27:670–681.
Ono M., Ohkouchi S., Kanehira M., Tode N., Kobayashi M., Ebina M., Nukiwa T., Irokawa T., Ogawa H., Akaike T.. Mesenchymal stem cells correct inappropriate epithelial-mesenchyme relation in pulmonary fibrosis using stanniocalcin-1.. Mol. Ther. 2015;23:549–560.
Lee K.C., Lin H.C., Huang Y.H., Hung S.C.. Allo-transplantation of mesenchymal stem cells attenuates hepatic injury through IL1Ra dependent macrophage switch in a mouse model of liver disease.. J. Hepatol. 2015;63:1405–1412.
Lee R.H., Yu J.M., Foskett A.M., Peltier G., Reneau J.C., Bazhanov N., Oh J.Y., Prockop D.J.. TSG-6 as a biomarker to predict efficacy of human mesenchymal stem/progenitor cells (hMSCs) in modulating sterile inflammation in vivo.. Proc. Natl. Acad. Sci. USA. 2014;111:16766–16771.
Luo Q., Zhang B., Kuang D., Song G.. Role of Stromal-Derived Factor-1 in Mesenchymal Stem Cell Paracrine-Mediated Tissue Repair.. Curr. Stem Cell Res. Ther. 2016;11:585–592.
Zhou P., Liu Z., Li X., Zhang B., Wang X., Lan J., Shi Q., Li D., Ju X.. Migration ability and Toll-like receptor expression of human mesenchymal stem cells improves significantly after three-dimensional culture.. Biochem. Biophys. Res. Commun. 2017;491:323–328.
Gentile P., Scioli M.G., Bielli A., Orlandi A., Cervelli V.. Concise Review: The Use of Adipose-Derived Stromal Vascular Fraction Cells and Platelet Rich Plasma in Regenerative Plastic Surgery.. Stem Cells 2017;35:117–134.
Canapp S.O., Canapp D.A., Ibrahim V., Carr B.J., Cox C., Barrett J.G.. The Use of Adipose-Derived Progenitor Cells and Platelet-Rich Plasma Combination for the Treatment of Supraspinatus Tendinopathy in 55 Dogs: A Retrospective Study.. Front. Vet. Sci. 2016;3:61.
Andreoli V, Berni P, Conti V, Ramoni R, Basini G, Grolli S. Mesenchymal Stromal Cells Derived from Canine Adipose Tissue: Evaluation of the Effect of Different Shipping Vehicles Used for Clinical Administration. Int J Mol Sci 2024 Mar 18;25(6).
Lu T, Zheng C, Fan Z. Cardamonin suppressed the migration, invasion, epithelial mesenchymal transition (EMT) and lung metastasis of colorectal cancer cells by down-regulating ADRB2 expression. Pharm Biol 2022 Dec;60(1):1011-1021.
Miguel-Pastor L, Satué K, Chicharro D, Torres-Torrillas M, Del Romero A, Peláez P, Carrillo JM, Cuervo B, Sopena JJ, Cerón JJ, Rubio M. Evaluation of a Standardized Protocol for Plasma Rich in Growth Factors Obtention in Cats: A Prospective Study. Front Vet Sci 2022;9:866547.
Uberti B, Plaza A, Henríquez C. Pre-conditioning Strategies for Mesenchymal Stromal/Stem Cells in Inflammatory Conditions of Livestock Species. Front Vet Sci 2022;9:806069.
Berni P, Leonardi F, Conti V, Ramoni R, Grolli S, Mattioli G. Case Report: A Novel Ventilated Thermoplastic Mesh Bandage for Post-operative Management of Large Soft Tissue Defects: A Case Series of Three Dogs Treated With Autologous Platelet Concentrates. Front Vet Sci 2021;8:704567.
Chang Y, Yang M, Ke S, Zhang Y, Xu G, Li Z. Effect of Platelet-Rich Plasma on Intervertebral Disc Degeneration In Vivo and In Vitro: A Critical Review. Oxid Med Cell Longev 2020;2020:8893819.
Suelzu CM, Conti V, Khalidy Y, Montagna S, Strusi G, Di Lecce R, Berni P, Basini G, Ramoni R, Grolli S. Xenobiotic-Free Medium Guarantees Expansion of Adipose Tissue-Derived Canine Mesenchymal Stem Cells Both in 3D Fibrin-Based Matrices and in 2D Plastic Surface Cultures. Cells 2020 Dec 2;9(12).
Gugjoo MB, Hussain S, Amarpal, Shah RA, Dhama K. Mesenchymal Stem Cell-Mediated Immuno-Modulatory and Anti- Inflammatory Mechanisms in Immune and Allergic Disorders. Recent Pat Inflamm Allergy Drug Discov 2020;14(1):3-14.
Kardos D, Simon M, Vácz G, Hinsenkamp A, Holczer T, Cseh D, Sárközi A, Szenthe K, Bánáti F, Szathmary S, Nehrer S, Kuten O, Masteling M, Lacza Z, Hornyák I. The Composition of Hyperacute Serum and Platelet-Rich Plasma Is Markedly Different despite the Similar Production Method. Int J Mol Sci 2019 Feb 8;20(3).