Pittenger MF, Discher DE, Peault BM, Phinney DG, Hare JM, Caplan AI. Mesenchymal stem cell perspective: cell biology to clinical progress. NPJ Regen Med. 2019;4:22.

Article  PubMed  PubMed Central  Google Scholar 

Trounson A, McDonald C. Stem cell therapies in clinical trials: progress and challenges. Cell Stem Cell. 2015;17(1):11–22.

Article  PubMed  CAS  Google Scholar 

Moll G, Ankrum JA, Kamhieh-Milz J, Bieback K, Ringdén O, Volk HD, Geissler S, Reinke P. Intravascular mesenchymal stromal/stem cell therapy product diversification: time for new clinical guidelines. Trends Mol Med. 2019;25(2):149–63.

Article  PubMed  Google Scholar 

Galipeau J, Krampera M, Leblanc K, Nolta JA, Phinney DG, Shi Y, Tarte K, Viswanathan S, Martin I. Mesenchymal stromal cell variables influencing clinical potency: the impact of viability, fitness, route of administration and host predisposition. Cytotherapy. 2021. This article by the International Society for Cell & Gene Therapy MSC committee outlines bottlenecks to reach clinical efficacy using MSCs.

Chinnadurai R, Garcia MA, Sakurai Y, Lam WA, Kirk AD, Galipeau J, Copland IB. Actin cytoskeletal disruption following cryopreservation alters the biodistribution of human mesenchymal stromal cells in vivo. Stem Cell Rep. 2014;3(1):60–72.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Dave C, Mei SH, McRae A, Hum C, Sullivan KJ, Champagne J, Ramsay T, McIntyre L. Comparison of freshly cultured versus cryopreserved mesenchymal stem cells in animal models of inflammation: a pre-clinical systematic review. eLife. 2022;11. This systematic review summarizes 257 studies, where MSCs were differently prepared prior to use in preclinical studies.

Cottle C, Porter AP, Lipat A, Turner-Lyles C, Nguyen J, Moll G, Chinnadurai R. Impact of cryopreservation and freeze-thawing on therapeutic properties of mesenchymal stromal/stem cells and other common cellular therapeutics. Curr Stem Cell Rep. 2022;8(2):72–92.

Najar M, Krayem M, Merimi M, Burny A, Meuleman N, Bron D, Raicevic G, Lagneaux L. Insights into inflammatory priming of mesenchymal stromal cells: functional biological impacts. Inflamm Res. 2018;67(6):467–77.

Article  PubMed  CAS  Google Scholar 

Noronha NC, Mizukami A, Caliari-Oliveira C, Cominal JG, Rocha JLM, Covas DT, Swiech K, Malmegrim KCR. Priming approaches to improve the efficacy of mesenchymal stromal cell-based therapies. Stem Cell Res Ther. 2019;10(1):131.

Article  PubMed  Google Scholar 

Liao Y, Fu Z, Huang Y, Wu S, Wang Z, Ye S, Zeng W, Zeng G, Li D, Yang Y, Pei K, Yang J, Hu Z, Liang X, Hu J, Liu M, Jin J, Cai C. Interleukin-18-primed human umbilical cord-mesenchymal stem cells achieve superior therapeutic efficacy for severe viral pneumonia via enhancing T-cell immunosuppression. Cell Death Dis. 2023;14(1):66.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Bernardo ME, Fibbe WE. Mesenchymal stromal cells: sensors and switchers of inflammation. Cell Stem Cell. 2013;13(4):392–402.

Article  PubMed  CAS  Google Scholar 

Zhou Y, Tsai TL, Li WJ. Strategies to retain properties of bone marrow-derived mesenchymal stem cells ex vivo. Ann N Y Acad Sci. 2017;1409(1):3–17.

Article  PubMed  PubMed Central  Google Scholar 

Petrenko Y, Sykova E, Kubinova S. The therapeutic potential of three-dimensional multipotent mesenchymal stromal cell spheroids. Stem Cell Res Ther. 2017;8(1):94.

Article  PubMed  PubMed Central  Google Scholar 

Hu C, Li L. Preconditioning influences mesenchymal stem cell properties in vitro and in vivo. J Cell Mol Med. 2018;22(3):1428–42.

Article  PubMed  PubMed Central  Google Scholar 

Kim DS, Jang IK, Lee MW, Ko YJ, Lee DH, Lee JW, Sung KW, Koo HH, Yoo KH. Enhanced immunosuppressive properties of human mesenchymal stem cells primed by interferon-gamma. EBioMedicine. 2018;28:261–73.

Article  PubMed  PubMed Central  Google Scholar 

Corbett JM, Hawthorne I, Dunbar H, Coulter I, Chonghaile MN, Flynn CM, English K. Cyclosporine A and IFNgamma licencing enhances human mesenchymal stromal cell potency in a humanised mouse model of acute graft versus host disease. Stem Cell Res Ther. 2021;12(1):238.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Baudry N, Starck J, Aussel C, Lund K, Aletti M, Duranteau J, Banzet S, Lataillade JJ, Vicaut E, Peltzer J. Effect of preconditioned mesenchymal stromal cells on early microvascular disturbance in a mouse sepsis model. Stem Cells Dev. 2019;28(24):1595–606.

Article  PubMed  CAS  Google Scholar 

Park SJ, Kim DS, Choi M, Han KH, Han JS, Yoo KH, Moon KS. Preclinical evaluation of interferon-gamma primed human Wharton’s jelly-derived mesenchymal stem cells. Hum Exp Toxicol. 2023;42:9603271231171650.

Article  PubMed  Google Scholar 

Guess AJ, Daneault B, Wang R, Bradbury H, La Perle KMD, Fitch J, Hedrick SL, Hamelberg E, Astbury C, White P, Overolt K, Rangarajan H, Abu-Arja R, Devine SM, Otsuru S, Dominici M, O’Donnell L, Horwitz EM. Safety profile of good manufacturing practice manufactured interferon gamma-primed mesenchymal stem/stromal cells for clinical trials. Stem Cells Transl Med. 2017;6(10):1868–79.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Galipeau J. Reply: “Function of cryopreserved mesenchymal stromal cells with and without interferon-gamma prelicensing is context dependent.” Stem cells. 2017;35(5):1440–1.

Article  PubMed  CAS  Google Scholar 

Szabo E, Fajka-Boja R, Kriston-Pal E, Hornung A, Makra I, Kudlik G, Uher F, Katona RL, Monostori E, Czibula A. Licensing by inflammatory cytokines abolishes heterogeneity of immunosuppressive function of mesenchymal stem cell population. Stem Cells Dev. 2015;24(18):2171–80.

Article  PubMed  CAS  Google Scholar 

Prasanna SJ, Gopalakrishnan D, Shankar SR, Vasandan AB. Pro-inflammatory cytokines, IFNgamma and TNFalpha, influence immune properties of human bone marrow and Wharton jelly mesenchymal stem cells differentially. PLoS ONE. 2010;5(2): e9016.

Article  PubMed  PubMed Central  Google Scholar 

Aktas E, Chamberlain CS, Saether EE, Duenwald-Kuehl SE, Kondratko-Mittnacht J, Stitgen M, Lee JS, Clements AE, Murphy WL, Vanderby R. Immune modulation with primed mesenchymal stem cells delivered via biodegradable scaffold to repair an Achilles tendon segmental defect. J Orthop Res. 2017;35(2):269–80.

Article  PubMed  CAS  Google Scholar 

Murphy N, Treacy O, Lynch K, Morcos M, Lohan P, Howard L, Fahy G, Griffin MD, Ryan AE, Ritter T. TNF-alpha/IL-1beta-licensed mesenchymal stromal cells promote corneal allograft survival via myeloid cell-mediated induction of Foxp3(+) regulatory T cells in the lung. FASEB J. 2019;33(8):9404–21.

Article  PubMed  CAS  Google Scholar 

Lynch K, Treacy O, Chen X, Murphy N, Lohan P, Islam MN, Donohoe E, Griffin MD, Watson L, McLoughlin S, O’Malley G, Ryan AE, Ritter T. TGF-beta1-licensed murine MSCs show superior therapeutic efficacy in modulating corneal allograft immune rejection in vivo. Mol Ther. 2020;28(9):2023–43.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Liu Q, Ji S, Xia T, Liu J, Liu Z, Chen X, Zang ZJ. MCP-1 priming enhanced the therapeutic effects of human mesenchymal stromal cells on contact hypersensitivity mice by activating the COX2-PGE2/STAT3 pathway. Stem Cells Dev. 2020;29(16):1073–83.

Li Y, Zhang Y, Tao Y, Huang X, Yu C, Xu H, Chen J, Xia K, Shi K, Zhang Y, Wang J, Shu J, Cheng F, Wang S, Liang C, Li F, Zhou X, Chen Q. metabolic glycoengineering: a promising strategy to remodel microenvironments for regenerative therapy. Stem Cells Int. 2023;2023:1655750.

Article  PubMed  PubMed Central  Google Scholar 

Rocamora F, Peralta AG, Shin S, Sorrentino J, Wu MYM, Toth EA, Fuerst TR, Lewis NE. Glycosylation shapes the efficacy and safety of diverse protein, gene and cell therapies. Biotechnol Adv. 2023;67:108206.

Article  PubMed  CAS  Google Scholar 

Kufleitner M, Haiber LM, Wittmann V. Metabolic glycoengineering - exploring glycosylation with bioorthogonal chemistry. Chem Soc Rev. 2023;52(2):510–35.

Article  PubMed  CAS  Google Scholar 

Sackstein R, Merzaban JS, Cain DW, Dagia NM, Spencer JA, Lin CP, Wohlgemuth R. Ex vivo glycan engineering of CD44 programs human multipotent mesenchymal stromal cell trafficking to bone. Nat Med. 2008;14(2):181–7.

Article  PubMed  CAS  Google Scholar 

Dimitroff CJ, Lee JY, Fuhlbrigge RC, Sackstein R. A distinct glycoform of CD44 is an L-selectin ligand on human hematopoietic cells. Proc Natl Acad Sci U S A. 2000;97(25):13841–6.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Linares LF, Lozano-Rivas N, Marras-Fernandez-Cid C, Garcia-Hernandez AM, Algueró MDC, Iniesta F, Sanchez-Salinas D, López-Lucas MD, Rodriguez-Valiente M, Cabañas V, García-Bernal D, Molina MDM, Lopez S, Ramirez-Tovar F, Ruiz Sará JE, García B, Blanquer M, Olmo Fernandez-Delgado JA, Espinosa M, Zamarro J, Becerra-Ratia J, Peris JL, López-Exposito I, Bafalliu JA, Ruiz-Espejo F, Domenech E, Morales-Cano MD, Arrabal PM, Soler G, Vera A, Guzman-Aroca F, Moraleda JM, Sackstein R. AB1011 Clinical trial of intravenous infusion of fucosylated bone marrow mesenchymal stem cells in patients with osteoporosis. Ann Rheum Dis. 2018;77(2):1.

Awan B, Turkov D, Schumacher C, Jacobo A, McEnerney A, Ramsey A, Xu G, Park D, Kalomoiris S, Yao W, Jao LE, Allende ML, Lebrilla CB, Fierro FA. FGF2 induces migration of human bone marrow stromal cells by increasing core fucosylations on N-glycans of integrins. Stem Cell Rep. 2018;11(2):325–33.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Sarkar D, Spencer JA, Phillips JA, Zhao W, Schafer S, Spelke DP, Mortensen LJ, Ruiz JP, Vemula PK, Sridharan R, Kumar S, Karnik R, Lin CP, Karp JM. Engineered cell homing. Blood. 2011;118(25):e184–91.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Zheng W, He R, Liang X, Roudi S, Bost J, Coly PM, van Niel G, Andaloussi SEL. Cell-specific targeting of extracellular vesicles though engineering the glycocalyx. J Extracell Vesicles. 2022;11(12):e12290.

Article  PubMed  Google Scholar 

Elbein AD, Tropea JE, Mitchell M, Kaushal GP. Kifunensine, a potent inhibitor of the glycoprotein processing mannosidase I. J Biol Chem. 1990;265(26):15599–605.

Article  PubMed  CAS  Google Scholar 

Alonso-Garcia V, Chaboya C, Li Q, Le B, Congleton TJ, Florez J, Tran V, Liu GY, Yao W, Lebrilla CB, Fierro FA. High mannose N-glycans promote migration of bone-marrow-derived mesenchymal stromal cells. Int J Mol Sci. 2020;21(19).

Yang Y, Lee EH, Yang Z. Hypoxia-conditioned mesenchymal stem cells in tissue regeneration application. Tissue Eng Part B Rev. 2022;28(5):966–77.

CAS