Intervertebral disc (IVD) degeneration is a major factor contributing to the development of back and neck pain, which represents a global burden for patients, clinicians, and the society. For patients with early signs and symptoms who are not responsive to conservative treatment but do not yet qualify for spine surgery, therapeutic options are scarce. Recently, intradiscal injection of mesenchymal stromal cells (MSCs) derived from bone marrow has shown promising outcome in patients suffering from discogenic low back pain. The therapeutic effect of locally delivered MSCs has been attributed to their secretion of immune-modulatory, anti-inflammatory, and regenerative mediators. Direct application of MSC secretome is therefore an attractive therapeutic approach, avoiding some of the hurdles and risks of cell injection.
GoalOne aim of this project is to evaluate the potential of MSC secretome for IVD regeneration using cell and organ culture models. First, the secretome of human MSCs stimulated with different human IVD conditioned media will be characterized to assess the MSCs response to the IVD environment. Secondly, the therapeutic effect of stimulated MSCs' secretome on IVD cells and tissues will be investigated. Composition of the secretome will be correlated to its regenerative effect to identify potent secretomes for further pre-clinical study.
Li Z, Gehlen Y, Heizmann F, Grad S, Alini M, Richards RG, Kubosch D, Südkamp N, Izadpanah K, Kubosch EJ and Lang G. Preclinical ex-vivo testing of anti-inflammatory drugs in a bovine intervertebral degenerative disc model. Front. Bioeng. Biotechnol. 8:583, 2020. doi: 10.3389/fbioe.2020.00583
Du J, Pfannkuche JJ, Lang G, Creemers LB, Alini M, Grad S, Li Z. Proinflammatory intervertebral disc cell and organ culture models induced by tumor necrosis factor alpha. JOR Spine. 2020 Jun 19;3(3):e1104. doi: 10.1002/jsp2.1104. eCollection 2020 Sep.
Zhou Z, Cui S, Du J, Richards RG, Alini M, Grad S, Li Z. One strike loading organ culture model to investigate the post-traumatic disc degenerative condition. J Orthop Transl 2020.
Cui S, Zhou Z, Liu X, Richards RG, Alini M, Peng S, Liu S, Zou X, Li Z, Grad S. Identification and characterization of serum microRNAs as biomarkers for human disc degeneration: An RNA sequencing analysis. Diagnostics (Basel). 2020 Dec 8;10(12):1063. doi: 10.3390/diagnostics10121063
Karppinen J, Koivisto K, Ketola J, Haapea M, Paananen M, Herzig KH, Alini M, Lotz J, Dudli S, Samartzis D, Risteli J, Majuri ML, Alenius H, Kyllönen E, Järvinen J, Niinimäki J, Grad S. Serum biomarkers for Modic changes in patients with chronic low back pain. Eur Spine J 2021
Karppinen J, Koivisto K, Ketola J, Haapea M, Paananen M, Herzig K-H, Alini M, Lotz J, Dudli S,Samartzis D, Risteli J, Majuri M-L, Alenius H, Kyllönen E, Järvinen J, Niinimäki J, Grad S.Serum biomarkers for Modic changes in patients with chronic low back pain. Eur Spine J. 2021;epub Jan 9. https://doi.org/10.1007/s00586-020-06713-z
Wangler S, Kamali A, Wapp C, Wuertz-Kozak K, Häckel S, Fortes C, Benneker LM, Haglund L, Richards RG, Alini M, Peroglio M, Grad S. Uncovering the secretome of mesenchymal stromal cells exposed to healthy, traumatic, and degenerative intervertebral discs: a proteomic analysis. Stem Cell Res Ther. 2021;12(1):11. https://doi.org/10.1186/s13287-020-02062-2
Kamali A, Ziadlou R, Lang G, Pfannkuche J, Cui S, Li Z, Richards RG, Alini M, Grad S. Small molecule-based treatment approaches for intervertebral disc degeneration: Current options and future directions. Theranostics. 2021;11(1):27-47. https://dx.doi.org/10.7150/thno.48987
Cui S, Zhou Z, Chen X, Wei F, Richards RG, Alini M, Grad S, Li Z. Transcriptional profiling of intervertebral disc in a post-traumatic early degeneration organ culture model. JOR Spine. 2021;epub April 8:e1146. https://doi.org/10.1002/jsp2.1146Croft AS, Illien-Jünger S, Grad S, Guerrero J, Wangler S, Gantenbein B. The application of mesenchymal stromal cells and their homing capabilities toregenerate the intervertebral disc. Int J Mol Sci. 2021;22(7):3519. https://doi.org/10.3390/ijms22073519Nüesch A. The influence of mesenchymal stromal cells secretome on nucleus pulposus cells exposed to a proinflammatory environment. 2021 ETH Zürich (Z. Li, S. Grad, S. Ferguson) - MSc ETH HST (thesis)
Russo F, Ambrosio L, Peroglio M, Guo W, Wangler S, Gewiess J, Grad S, Alini M, Papalia R, Vadalà G, Denaro V. A hyaluronan and platelet-rich plasma hydrogel for mesenchymal stem cell delivery in the intervertebral disc: An organ culture study. Int J Mol Sci. 2021;22(6):2963
Ren W, Cui S, Alini M, Grad S, Zhou Q, Li Z, Razansky D. Noninvasive multimodal fluorescence and magnetic resonance imaging of whole-organ intervertebral discs. Biomed Opt Express. 2021;12(6):3214-27. https://doi.org/10.1364/BOE.421205
Russo F, Ambrosio L, Peroglio M, Wangler S, Guo W, Grad S, Alini M, Vadalà G, Papalia R, Denaro V. Human mesenchymal stem cells encapsulated in hyaluronic acid and platelet-rich plasma modulate matrix synthesis ex vivo. 2020 EORS virtual (poster)
Cui S, Zhou Z, Alini M, Grad S, Li Z. High impact loading organ culture model to investigate the post-traumatic disc degenerative condition. 2020 GR forscht virtual (oral)
Wangler S, Kamali A, Wapp C, Wuertz-Kozak K, Häckel S, Fortes C, Benneker LM, Haglund L, Richards RG, Alini M, Peroglio M, Grad S.Mesenchymal stem cell secretome: A potential anabolic and immunomodulatory therapy for modulation of early intervertebral disc degeneration. 2021 ORS virtual (oral)