Improving mesenchymal stem/stromal cell potency and survival

Proceedings from the International Society of Cell Therapy (ISCT) MSC preconference held in May 2018, Palais des Congrès de Montréal, Organized by the ISCT MSC Scientific Committee
Published:February 14, 2020DOI:


      As part of the International Society of Cell Therapy (ISCT) 2018 Annual Meeting, the Mesenchymal Stem/Stromal Cell (MSC) committee organized a pre-conference, which covered methods of improving MSC engraftment and potency in vivo and clinical efficacy using MSC potency assays. The speakers examined methods to improve clinical efficacy using MSC potency assays and methods to improve MSC engraftment/homing/potency in vivo. Discussion of patient “responders” versus “non-responders” in clinical trials and working toward ways to identify them were also included.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Cytotherapy
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Viswanathan S.
        • Shi Y.
        • Galipeau J.
        • Krampera M.
        • Leblanc K.
        • Martin I.
        • et al.
        Mesenchymal stem versus stromal cells: International Society for Cell & Gene Therapy (ISCT(R)) Mesenchymal Stromal Cell committee position statement on nomenclature.
        Cytotherapy. 2019; 21: 1019-1024
        • Andrzejewska A.
        • Lukomska B.
        • Janowski M.
        Concise Review: Mesenchymal Stem Cells: From Roots to Boost.
        Stem Cells. 2019; 37: 855-864
        • Martin I.
        • Galipeau J.
        • Kessler C.
        • Le Blanc K.
        • Dazzi F.
        Challenges for mesenchymal stromal cell therapies.
        Science translational medicine. 2019; 11: 1-3
        • Galipeau J.
        • Sensebe L.
        Mesenchymal Stromal Cells: Clinical Challenges and Therapeutic Opportunities.
        Cell Stem Cell. 2018; 22: 824-833
        • Boregowda S.V.
        • Krishnappa V.
        • Haga C.L.
        • Ortiz L.A.
        • Phinney D.G.
        A Clinical Indications Prediction Scale Based on TWIST1 for Human Mesenchymal Stem Cells.
        EBioMedicine. 2016; 4: 62-73
        • Haga C.L.
        • Phinney D.G.
        MicroRNAs in the imprinted DLK1-DIO3 region repress the epithelial-to-mesenchymal transition by targeting the TWIST1 protein signaling network.
        The Journal of biological chemistry. 2012; 287: 42695-42707
        • Lai W.T.
        • Krishnappa V.
        • Phinney D.G.
        Fibroblast growth factor 2 (Fgf2) inhibits differentiation of mesenchymal stem cells by inducing Twist2 and Spry4, blocking extracellular regulated kinase activation, and altering Fgf receptor expression levels.
        Stem Cells. 2011; 29: 1102-1111
        • Phinney D.G.
        Twist, epithelial-to-mesenchymal transition, and stem cells.
        Stem Cells. 2011; 29: 3-4
        • Klinker M.W.
        • Marklein R.A.
        • Lo Surdo J.L.
        • Wei C.H.
        • Bauer S.R.
        Morphological features of IFN-gamma-stimulated mesenchymal stromal cells predict overall immunosuppressive capacity.
        Proceedings of the National Academy of Sciences of the United States of America. 2017; 114: E2598-E2607
        • Foppiani E.M.
        • Candini O.
        • Mastrolia I.
        • Murgia A.
        • Grisendi G.
        • Samarelli A.V.
        • et al.
        Impact of HOXB7 overexpression on human adipose-derived mesenchymal progenitors.
        Stem Cell Res Ther. 2019; 10: 101
        • Francois M.
        • Copland I.B.
        • Yuan S.
        • Romieu-Mourez R.
        • Waller E.K.
        • Galipeau J.
        Cryopreserved mesenchymal stromal cells display impaired immunosuppressive properties as a result of heat-shock response and impaired interferon-gamma licensing.
        Cytotherapy. 2012; 14: 147-152
        • Moll G.
        • Alm J.J.
        • Davies L.C.
        • von Bahr L.
        • Heldring N.
        • Stenbeck-Funke L.
        • et al.
        Do cryopreserved mesenchymal stromal cells display impaired immunomodulatory and therapeutic properties?.
        Stem Cells. 2014; 32: 2430-2442
        • Chinnadurai R.
        • Garcia M.A.
        • Sakurai Y.
        • Lam W.A.
        • Kirk A.D.
        • Galipeau J.
        • et al.
        Actin cytoskeletal disruption following cryopreservation alters the biodistribution of human mesenchymal stromal cells in vivo.
        Stem Cell Reports. 2014; 3: 60-72
        • Beegle J.
        • Lakatos K.
        • Kalomoiris S.
        • Stewart H.
        • Isseroff R.R.
        • Nolta J.A.
        • et al.
        Hypoxic preconditioning of mesenchymal stromal cells induces metabolic changes, enhances survival, and promotes cell retention in vivo.
        Stem Cells. 2015; 33: 1818-1828
        • Binder B.Y.
        • Sondergaard C.S.
        • Nolta J.A.
        • Leach J.K.
        Lysophosphatidic acid enhances stromal cell-directed angiogenesis.
        PloS one. 2013; 8: e82134
        • Lakatos K.
        • Kalomoiris S.
        • Merkely B.
        • Nolta J.A.
        • Fierro F.A.
        Mesenchymal Stem Cells Respond to Hypoxia by Increasing Diacylglycerols.
        Journal of cellular biochemistry. 2016; 117: 300-307
        • Rosova I.
        • Dao M.
        • Capoccia B.
        • Link D.
        • Nolta J.A.
        Hypoxic preconditioning results in increased motility and improved therapeutic potential of human mesenchymal stem cells.
        Stem Cells. 2008; 26: 2173-2182
        • Moya A.
        • Paquet J.
        • Deschepper M.
        • Larochette N.
        • Oudina K.
        • Denoeud C.
        • et al.
        Human Mesenchymal Stem Cell Failure to Adapt to Glucose Shortage and Rapidly Use Intracellular Energy Reserves Through Glycolysis Explains Poor Cell Survival After Implantation.
        Stem Cells. 2018; 36: 363-376
        • Cortez-Toledo E.
        • Rose M.
        • Agu E.
        • Dahlenburg H.
        • Yao W.
        • Nolta J.A.
        • et al.
        Enhancing Retention of Human Bone Marrow Mesenchymal Stem Cells with Prosurvival Factors Promotes Angiogenesis in a Mouse Model of Limb Ischemia.
        Stem Cells Dev. 2019; 28: 114-119
        • Rashedi I.
        • Talele N.
        • Wang X.H.
        • Hinz B.
        • Radisic M.
        • Keating A.
        Collagen scaffold enhances the regenerative properties of mesenchymal stromal cells.
        PloS one. 2017; 12e0187348
        • McIntyre L.A.
        • Stewart D.J.
        • Mei S.H.J.
        • Courtman D.
        • Watpool I.
        • Granton J.
        • et al.
        Cellular Immunotherapy for Septic Shock. A Phase I Clinical Trial.
        Am J Respir Crit Care Med. 2018; 197: 337-347
        • Le Blanc K.
        • Frassoni F.
        • Ball L.
        • Locatelli F.
        • Roelofs H.
        • Lewis I.
        • et al.
        Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study.
        Lancet. 2008; 371: 1579-1586
        • Ball L.M.
        • Bernardo M.E.
        • Roelofs H.
        • van Tol M.J.
        • Contoli B.
        • Zwaginga J.J.
        • et al.
        Multiple infusions of mesenchymal stromal cells induce sustained remission in children with steroid-refractory, grade III-IV acute graft-versus-host disease.
        British journal of haematology. 2013; 163: 501-509
        • Gavin C.
        • Boberg E.
        • Von Bahr L.
        • Bottai M.
        • Andren A.T.
        • Wernerson A.
        • et al.
        Tissue immune profiles supporting response to mesenchymal stromal cell therapy in acute graft-versus-host disease-a gut feeling.
        Stem Cell Res Ther. 2019; 10: 334
        • Arzi B.
        • Clark K.C.
        • Sundaram A.
        • Spriet M.
        • Verstraete F.J.M.
        • Walker N.J.
        • et al.
        Therapeutic Efficacy of Fresh, Allogeneic Mesenchymal Stem Cells for Severe Refractory Feline Chronic Gingivostomatitis.
        Stem cells translational medicine. 2017; 6: 1710-1722
        • Panes J.
        • Garcia-Olmo D.
        • Van Assche G.
        • Colombel J.F.
        • Reinisch W.
        • Baumgart D.C.
        • 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. 2016; 388: 1281-1290
        • Matthay M.A.
        • Calfee C.S.
        • Zhuo H.
        • Thompson B.T.
        • Wilson J.G.
        • Levitt J.E.
        • et al.
        Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): a randomised phase 2a safety trial.
        Lancet Respir Med. 2019; 7: 154-162
        • Jackson M.V.
        • Morrison T.J.
        • Doherty D.F.
        • McAuley D.F.
        • Matthay M.A.
        • Kissenpfennig A.
        • et al.
        Mitochondrial Transfer via Tunneling Nanotubes is an Important Mechanism by Which Mesenchymal Stem Cells Enhance Macrophage Phagocytosis in the In Vitro and In Vivo Models of ARDS.
        Stem Cells. 2016; 34: 2210-2223
        • Phinney D.G.
        • Galipeau J.
        MSC Committee of the ISCT. Manufacturing mesenchymal stromal cells for clinical applications: A survey of Good Manufacturing Practices at U.S. academic centers.
        Cytotherapy. 2019; 21: 782-792