Professor Stan Gronthos

• Biography/ Background

  Prof. Stan Gronthos, PhD, is a National Health and Medical Research Principal Reserach Fellow. His research specialty is in stem cell biology and regenerative medicine. He is Founder and Head of the Mesenchymal Stem Cell Laboratory in the School of Medicine, Faculty of Health Sciences, University of Adelaide. He is also Co-Director of the Centre for Stem Cell Research, University of Adelaide. In 2014, the Mesenchymal Stem Cell Laboratory moved to the South Australian Health and Medical Reserach Institute (SAHMRI) on North Terrace, adjacent to the new Royal Adelaide Hospital site. 

• Research Interests

   

  The focus of the Mesenchymal Stem Cell Laboratory is to investigate the origin and biological properties of different postnatal mesenchymal stem cell (MSC) populations, that give rise to supportive connective tissues such as myelosupportive stroma, adipose tissue, smooth muscle, cardiac muscle, bone, cartilage, ligament, cementum and dentin. Our work seeks to identify critical genes and epigenetic factors that regulate MSC self-renewal, proliferation and differentiation. In addition, research efforts have focused on identifying the factors central to MSC mediated regulation of haematopiesis, angiogenesis and immune cell modulation. Importantly, many of these molecular processes are considered underlying causes of chronic diseases and tumour cell development. Together with Prof. Andrew Zannettino and our commercial partner (Mesoblast Ltd), our basic research activities have progressed into Phase II/III human clinical trails for orthopaedic, cardiovascular, cancer and immune based indications. Our continuing research into the basic properties of MSC will help develop more effective and safer stem cell based therapeutic options in the future for a wide variety of clinical diseases and conditions.

   

• Publications

  SELECTED PUBLICATIONS 

  Gronthos S, Ohta S, Graves SE, Simmons PJ (1994). The STRO-1+ fraction of adult human bone marrow contains the osteogenic precursors. BLOOD, 84 (12): 4164-4173. 

  Gronthos S, and Simmons PJ (1995). The growth factor requirements of STRO-1+ human bone marrow stromal precursors under serum-deprived conditions. BLOOD, 85 (4): 929-940. 

  Gronthos S, Zannettino ACW, Graves SE, Ohta S, Hay SJ, Simmons PJ (1999). Differential cell surface expression of the STRO-1 and alkaline phosphatase antigens on discrete developmental stages in primary cultures of human bone cells. Journal of Bone and Mineral Research, 14(1): 48-57.

  Gronthos S, Mankani M, Brahim J, Gehron Robey P, Shi S (2000). Post-Natal Human Dental Pulp Stem Cells In vitro and In vivo. Proceedings of the National Academy of Sciences (USA), 97 (25): 13625-13630. 

  Bianco P, Riminucci M, Gronthos S, Gehron Robey P (2001). Bone Marrow Stromal Stem Cells: Nature, Biology, and Potential Applications. Stem Cells, 19(3):180-192. 

  Gronthos S, Simmons PJ, Graves SE and Gehron Robey PG (2001). Integrin mediated interactions between human bone marrow stromal precursor cells and the extracellular matrix. Bone, 28 (2): 174-181.

  Kuznetsov SA, Mankani MH, Gronthos S, Satomura K, Bianco P, Gehron Robey P (2001). Circulating skeletal stem cells. Journal of Cell Biology, 153 (5): 1133-1139.

  Gronthos S, Dawn M, Franklin DM, Holly A, Leddy HA, Gehron Robey P, Storms RW, and Gimble JM (2001). Surface Protein Characterization of Human Adipose Tissue-Derived Stromal Cells. Journal of Cellular Physiology 189: 54-63. 

  Shi S, Gehron Robey P and Gronthos S (2001). Comparison of gene expression profile between human dental pulp stem cells and human bone marrow stromal stem cells by microarray analysis. Bone, 29(6): 532-539. 

  Shi S*, Gronthos S*, Chen S, Reddi A, Counter CM, Robey PG, Wang CY (2002). Bone formation by human postnatal bone marrow stromal stem cells is enhanced by telomerase expression. Nature Biotechnology, 20(6): 587-591.  

  Gronthos S, Brahim J, Li W, Fisher LW, Cherman N, Boyde A, DenBesten P, Gehron Robey PG and Shi S (2002). Stem Cell Properties of Human Dental Pulp Stem Cells. Journal of Dental Research, 81(8): 531-535.

  Gronthos S., Zannettino ACW, Kortesidis A, Shi S, Graves SE, Hay SJ, Simmons PJ (2003). Molecular and cellular characterisation of highly purified human bone marrow stromal stem cells. Journal of Cell Science 116: 1827-1835. 

  Gronthos S., Chen S., Wang C-Y., Robey P.G., and Shi S. (2003). Telomerase Accelerates Osteogenesis of Bone Marrow Stromal Stem Cells by Increasing Proliferation and by Up-regulation of CBFA1, Osterix, and Osteocalcin. Journal of Bone and Mineral Research, 18(4): 716-722.  

  Shi S. and Gronthos S. (2003). Perivascular Niche of Postnatal Mesenchymal Stem Cells in Human Bone Marrow and Dental Pulp. Journal of Bone and Mineral Research, 18(4): 696-704.

  Masako Miura, Stan Gronthos, Mingrui Zhao, Bai Lu, Larry W. Fisher, Pamela Gehron Robey, and Songtao (2003). Shi. SHED: Stem Cells from Human Exfoliated Deciduous Teeth. Proceedings of the National Academy of Sciences (USA), 100 (10): 5807-5812.

  Seo BM, Miura M, Gronthos S, Bartold PM, Batouli S, Brahim J, Young M, Robey PG, Wang PC and Shi S (2004). Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 364 (9429): 194-155.

  Zannettino ACW, Farrugia AN, Kortesidis A, Manavis J, To LB, Martin SK, Diamond P, Tamamura H5, Lapidot T6, Fujii N, Gronthos S (2005). Elevated Serum Levels of SDF-1α are Associated with Increased Osteoclast Activity and Osteolytic Bone Disease in Multiple Myeloma Patients. Cancer Research 65(5):1700-1709.  

  Kortesidis A, Zannettino ACW, Isenmann S, Shi S, Lapidot Tsvee L, and Gronthos S (2005). Stromal derived factor-1 promotes the growth, survival and development of human bone marrow stromal stem cells. BLOOD. 105(10):3793-3801.

  Miura Y, Miura M, Gronthos S, Allen MR, Cao C, Uveges TE, Bi Y, Ehirchiou D, Kortesidis A, Shi S, Zhang L. (2005). Defective osteogenesis of the stromal stem cells predisposes CD18-null mice to osteoporosis. Proc Natl Acad Sci U S A. 102(39):14022-7. 

  Martens TP, See F, Schuster MD, Sondermeijer HP, Hefti MM, Zannettino A, Gronthos S, Seki T, Itescu S (2006). Mesenchymal lineage precursor cells induce vascular network formation in ischemic myocardium. Nature Clinical Practice. Cardiovascular Medicine. Mar;3 Suppl 1(S1):S18-S22.   

  Gronthos S and Zannettino ACW (2006). Potential of bone marrow stromal stem cells to repair bone defects and fractures. Journal of Stem Cells, 1(1): 35-46. 

  Gronthos S, Mrozik K, Shi S, Bartold PM (2006). Ovine Periodontal Ligament Stem Cells: Isolation, Characterization and Differentiation Potential. Calcified Tissue International. 79(5):310-7. 

  Martin SK, Dewar AL, Farrugia AN, Horvath N, Gronthos S, To LB, Zannettino AC. (2006). Tumor angiogenesis is associated with plasma levels of stromal-derived factor-1alpha in patients with multiple myeloma. Clinical Cancer Research. 12(23):6973-6977. 

  Stokowski A, Shi S, Sun T, Bartold PM, Koblar SA, S Gronthos S (2007). EphB/ephrin-B interaction mediates adult stem cell attachment, spreading and migration: implications for dental tissue repair. Stem Cells. 25:156-164. 

  Isenmann S, Cakouros D, Zannettino A, Shi S, Gronthos S. (2007). hTERT Transcription Is Repressed By Cbfa1 in Human Mesenchymal Stem Cell Populations. Journal of Bone and Miner Research. 22(6):897-906. 

  Gronthos S, Fitter S, Diamond P, Paul J. Simmons PJ, Silviu Itescu I, Zannettino ACW (2007) A Novel Monoclonal Antibody (STRO-3) Identifies an Isoform of Tissue Non-Specific Alkaline Phosphatase Expressed by Multipotential Bone Marrow Stromal Stem Cells. Stem Cells and Development 16(6):953-963. 

  Zannettino ACW, Paton S, Kortesidis A, Khor F, Itescu S, Gronthos S (2007). Human Mulipotential Stromal Stem Cells are Derived from a Discrete Subpopulation of STRO-1bright/CD34-/CD45-/Glycophorin-A- Bone Marrow Cells. Haematologica. 92 1707-1708. 

  Zannettino AC, Paton S, Arthur A, Khor F, Itescu S, Gimble JM, Gronthos S (2008).  Multipotential human adipose-derived stromal stem cells exhibit a perivascular phenotype in vitro and in vivo. Journal of Cellular Physiology. 214(2):413-421. 

  Liu Y, Zheng Y, Ding G, Fang D, Zhang C, Bartold PM, Gronthos S, Shi S, Wang S. (2008). Periodontal Ligament Stem Cell-mediated Treatment for Periodontitis in Miniature Swine. Stem Cells. 26(4):1065-1073. 

  Arthur A, Rychkov G, Shi S, Koblar SA, Gronthos S. (2008). Adult Human Dental Pulp Stem Cells Differentiate Towards Functionally Active Neurons Under Appropriate Environmental Cues. Stem Cells, 26(7):1787-1795.

  Arthur A, Zannettino ACW, Gronthos S. (2009). The Therapeutic Applications of Multipotential Mesenchymal / Stromal Stem Cells in Skeletal Tissue Repair. Journal of Cellular Physiology. 218(2):237-45. 

  Wada N, Menicanin D, Shi S, Bartold PM, Gronthos S (2009). Immunomodulatory properties of human periodontal ligament stem cells. Journal of Cellular Physiology. 219(3):667-76. 

  Gronthos S, McCarty R, Mrozik, Krzysztof, Fitter, S, Paton S, Menicanin D, Itescu S, Bartold PM, Cory X, Zannettino A (2009).  Heat shock protein-90 (Hsp90) is expressed at the surface of multipotential mesenchymal precursor cells (MPC): Generation of a novel monoclonal antibody STRO-4, with specificity for MPC from human and ovine tissues. Stem Cells and Development. 18(9):1253-62.

  Arthur A, Shi S, Zannettino AC, Fujii N, Gronthos S*, Koblar SA*. (2009). Implanted Adult Human Dental Pulp Stem Cells Induce Endogenous Axon Guidance. Stem Cells. 27(9):2229-37. 

  Isenmann S, Arthur A, Zannettino AC, Turner JL, Shi S, Glackin CA, Gronthos S (2009). TWIST family of basic Helix-Loop-Helix Transcription Factors Mediate Human Mesenchymal Stromal/Stem Cell Growth and Commitment. Stem Cells. 27(10):2457-68.

  Menicanin D, Bartold PM, Zannettino AC, Gronthos S (2010). Identification of a Common Gene Expression Signature Associated with Immature Clonal Mesenchymal Cell Populations derived from Bone Marrow and Dental Tissues. Stem Cells and Development. 19(10):1501-10.

  Psaltis PJ, Paton S, See F, Arthur A, Martin S, Itescu S, Worthley SG, *Gronthos S, *Zannettino AC (2010). Enrichment for STRO-1 expression enhances the cardiovascular paracrine activity of human bone marrow-derived mesenchymal cell populations. Journal of Cellular Physiology. 223(2):530-40. 

  Ghosh P, Wu J, Shimmon S, Zannettino AC, Gronthos S, Itescu S (2010). Pentosan polysulfate promotes proliferation and chondrogenic differentiation of adult human bone marrow-derived mesenchymal precursor cells. Arthritis Research and Therapy. Feb 18;12(1):R28. [Epub ahead of print].

  Martin SK, Fitter S, Bong LF, Drew JJ, Gronthos S, Shepherd PR, Zannettino AC (2010). NVP-BEZ235, a dual pan class I PI3 kinase and mTOR inhibitor, promotes osteogenic differentiation in human mesenchymal stromal cells. Journal of Bone and Mineral Research. 25(10):2126-37.

  Peter J Psaltis, Angelo Carbone, Adam J Nelson, Dennis H Lau, Troy Jantzen, Jim Manavis, Kerry Williams, Silviu Itescu, Prashanthan Sanders, Stan Gronthos, Andrew CW Zannettino, Stephen G Worthley (2010). Reparative Effects of Allogeneic Mesenchymal Precursor Cells Delivered Transendocardially in Experimental Nonischemic Cardiomyopathy. Journal of the American College of Cardiology: Cardiovascular Interventions. 3(9): 974-983.

  Goldschlager T, Ghosh P, Zannettino A, Gronthos S, Rosenfeld JV, Itescu S, Jenkin G. Cervical motion preservation using mesenchymal progenitor cells and pentosan polysulfate, a novel chondrogenic agent: preliminary study in an ovine model. Neurosurgical Focus. 2010 Jun; 28(6):E4.

  Zannettino AC, Paton S, Itescu S, Gronthos S (2010). Comparative Assessment of the Osteoconductive Properties of Different Biomaterials In Vivo Seeded With Human or Ovine Mesenchymal Stem/Stromal Cells. Tissue Engineering Part A. 16(12):3579-87.

  Wada N, Bartold PM, Gronthos S (2011). Human Foreskin Fibroblasts Exert Immunomodulatory Properties by a Different Mechanism to Bone Marrow Mesenchymal Stem Cells. Stem Cells and Development. 20(4):647-59.

  Arthur A, Zannettino A, Panagopoulos R, Koblar SA, Sims NA, Stylianou C, Matsuo K, Gronthos S (2011). EphB/ephrin-B interactions mediate human MSC attachment, migration and osteochondral differentiation. Bone. 48(3):533-42.

  See F, Seki T, Psaltis PJ, Sondermeijer HP, Gronthos S, Zannettino AC, Govaert KM, Schuster MD, Kurlansky PA, Kelly DJ, Krum H, Itescu S (2011). Therapeutic Effects of Human STRO-3-Selected Mesenchymal Precursor Cells and their Soluble Factors in Experimental Myocardial Ischemia. Journal of Cellular and Molecular Medicine. 15(10):2117-29.

  Field JR, McGee M, Stanley R, Ruthenbeck G, Papadimitrakis T, Zannettino A, Gronthos S, Itescu S (2011). The efficacy of allogeneic mesenchymal precursor cells for the repair of an ovine tibial segmental defect. Vet Comp Orthop Traumatol. 24(2):113-121.

  Wada N, Wang B, Lin NH, Laslett AL, Gronthos S, Bartold PM (2011). Induced pluripotent stem cell lines derived from human gingival fibroblasts and periodontal ligament fibroblasts. Journal of Periodontal Research. 46(4):438-47.

  Xiong J, Mrozik KM, Gronthos S*, Bartold PM* (2012). Epithelial Cell Rests of Malassez contain unique stem cell populations capable of undergoing epithelial-mesenchymal transition. Stem Cells and Development. 21(11):2012-25. 

  Cakouros D, Isenmann S, Cooper L, Zannettino A, Anderson P, Glackin C, Gronthos S (2012). Twist-1 induces Ezh2 recruitment regulating histone methylation along the Ink4A/Arf locus in mesenchymal stem cells. Mol Cell Biol. 32(8):1433-1441.

  Ghosh P, Moore R, Vernon-Roberts B, Goldschlager T, Pascoe D, Zannettino A, Gronthos S, Itescu S (2012). Immunoselected STRO-3(+) mesenchymal precursor cells and restoration of the extracellular matrix of degenerate intervertebral discs. J Neurosurg Spine. 16(5):479-88.

  Leong WK, Henshall TL, Arthur A, Kremer KL, Lewis MD, Helps SC, Field J, Hamilton-Bruce MA, Warming S, Manavis J, Vink R, Gronthos S+, Koblar SA+ (2012). Human adult dental pulp stem cells enhance post stroke functional recovery through non-neural replacement mechanisms. Stem Cells Transplantational Medicine. 1(3):177-187.

  Arthur A, Panagopoulos RA, Cooper L, Menicanin D, Parkinson IH, Codrington JD, Vandyke K, Zannettino AC, Koblar SA, Sims NA, Matsuo K, Gronthos S (2013). EphB4 enhances the process of endochondral ossification and inhibits remodelling during bone fracture repair. J Bone Miner Res. 28(4):926-35.

  Hynes K, Menicanin D, Han J, Marino V, Mrozik K, Gronthos S, Bartold PM. (2013). Mesenchymal stem cells from iPS cells facilitate periodontal regeneration. J Dental Research. 92(9):833-839. 

  Richardson JD, Bertaso AG, Psaltis PJ, Frost L, Carbone A, Paton S, Nelson AJ, Wong DT, Worthley MI, Gronthos S*, Zannettino AC*, Worthley SG* (2013). Impact of timing and dose of mesenchymal stromal cell therapy in a preclinical model of acute myocardial infarction. J Card Fail. May;19(5):342-353.

  Richardson JD, Psaltis PJ, Frost L, Paton S, Carbone A, Bertaso AG, Nelson AJ, Wong DT, Worthley MI, Gronthos S*, Zannettino AC*, Worthley SG*. Incremental benefits of repeated mesenchymal stromal cell administration compared with solitary intervention after myocardial infarction. Cytotherapy. 2014 Apr;16(4):460-70. 

  Nguyen T, Arthur A, Hayball J, Gronthos S (2013). EphB and ephrin-B interactions mediate human mesenchymal stem cell suppression of activated T-cells. Stem Cells Dev. 22(20): 2751-2764.

  Mrozik KM, Wada N, Marino V, Richter W, Shi S, Wheeler DL, Gronthos S, Bartold PM. Regeneration of periodontal tissues using allogeneic periodontal ligament stem cells in an ovine model. Regen Med. 2013 Nov;8(6):711-723.

  Hemming S, Cakouros D, Isenmann S, Cooper L, Menicanin D, Zannettino A, Gronthos S. EZH2 and KDM6A act as an epigenetic switch to regulate mesenchymal stem cell lineage specification. Stem Cells. 2014 Mar;32(3):802-15.

  Hynes K, Menicanin D, Mrozik KM, Gronthos S, Bartold PM. Generation of functional mesenchymal stem cells from different induced pluripotent stem cell lines. Stem Cells Dev. 2014 May 15;23(10):1084-96.

  Menicanin D, Mrozik KM, Wada N, Marino V, Shi S, Bartold PM, Gronthos S. Periodontal Ligament Derived Stem Cells Exhibit the Capacity for Long-Term Survival, Self-Renewal and Regeneration of Multiple Tissue Types in Vivo. Stem Cells Dev.  2014 May 1;23(9):1001-11.

  Cakouros D, Isenmann S, Hemming SE, Menicanin D, Camp E, Zannettino AC, Gronthos S (2015). Novel basic Helix Loop Helix Transcription Factor Hes4 Antagonizes the Function of Twist-1 to Regulate Lineage Commitment of Bone Marrow Stromal/ Stem Cells. Stem Cells Dev. 24(11):1297-1308.

  Nguyen TN, Arthur A, Romana P, Paton S, Hayball JD, Zannettino ACW, Purton LE, Matsuo K and Gronthos S (2015). EphB4 expressing stromal cells exhibit an enhanced capacity for hematopoietic stem cell maintenance. Stem Cells. 33:2838-2849.

  Sivanathan KN, Rojas-Canales D, Hope CM, Krishnan R, Carroll RP, Gronthos S, Grey ST, Coates PT. Interleukin-17A induced human Mesenchymal Stem Cells are superior modulators of immunological function. Stem Cells. 2015 Jun 2. doi: 10.1002/ stem.2075. [Epub ahead of print].

   

Entry last updated: Tuesday, 29 Mar 2022

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