Emerging understanding of apoptosis in mediating mesenchymal stem cell therapy
  • 1.

    McCulloch, E. A. & Till, J. E. The radiation sensitivity of normal mouse bone marrow cells, determined by quantitative marrow transplantation into irradiated mice. Radiat. Res. 13, 115–125 (1960).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 2.

    Friedenstein, A. J., Chailakhjan, R. K. & Lalykina, K. S. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet. 3, 393–403 (1970).

    CAS  PubMed  PubMed Central  Google Scholar 

  • 3.

    Friedenstein, A. J., Chailakhyan, R. K., Latsinik, N. V., Panasyuk, A. F. & Keiliss-Borok, I. V. Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation 17, 331–340 (1974).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 4.

    Horwitz, E. M. et al. Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone. Proc. Natl Acad. Sci. USA 99, 8932–8937 (2002).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 5.

    Le Blanc, K. et al. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 371, 1579–1586 (2008).

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  • 6.

    Lee, R. H. et al. Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell 5, 54–63 (2009).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 7.

    Luger, D. et al. Intravenously delivered mesenchymal stem cells: systemic anti-inflammatory effects improve left ventricular dysfunction in acute myocardial infarction and ischemic cardiomyopathy. Circ. Res. 120, 1598–1613 (2017).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 8.

    Carr, M. J. et al. Mesenchymal precursor cells in adult nerves contribute to mammalian tissue repair and regeneration. Cell Stem Cell 24, 240–56 e9 (2019).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 9.

    Gao, F. et al. Mesenchymal stem cells and immunomodulation: current status and future prospects. Cell Death Dis. 7, e2062 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 10.

    Varderidou-Minasian, S. & Lorenowicz, M. J. Mesenchymal stromal/stem cell-derived extracellular vesicles in tissue repair: challenges and opportunities. Theranostics 10, 5979–5997 (2020).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 11.

    Zaborowski, M. P., Balaj, L., Breakefield, X. O. & Lai, C. P. Extracellular vesicles: composition, biological relevance, and methods of study. Bioscience 65, 783–797 (2015).

    PubMed  PubMed Central  Article  Google Scholar 

  • 12.

    He, C., Zheng, S., Luo, Y. & Wang, B. Exosome theranostics: biology and translational medicine. Theranostics 8, 237–255 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 13.

    Zhu, L. P. et al. Hypoxia-elicited mesenchymal stem cell-derived exosomes facilitates cardiac repair through miR-125b-mediated prevention of cell death in myocardial infarction. Theranostics 8, 6163–6177 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 14.

    Eirin, A. et al. Mesenchymal stem cell-derived extracellular vesicles attenuate kidney inflammation. Kidney Int 92, 114–124 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 15.

    Zhu, Y. G. et al. Human mesenchymal stem cell microvesicles for treatment of Escherichia coli endotoxin-induced acute lung injury in mice. Stem Cells 32, 116–125 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 16.

    Shigemoto-Kuroda, T. et al. MSC-derived extracellular vesicles attenuate immune responses in two autoimmune murine models: type 1 diabetes and uveoretinitis. Stem Cell Rep. 8, 1214–1225 (2017).

    CAS  Article  Google Scholar 

  • 17.

    Kerr, J. F., Wyllie, A. H. & Currie, A. R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 26, 239–257 (1972).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 18.

    Fuchs, Y. & Steller, H. Programmed cell death in animal development and disease. Cell 147, 742–758 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 19.

    Nagata, S., Hanayama, R. & Kawane, K. Autoimmunity and the clearance of dead cells. Cell 140, 619–630 (2010).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 20.

    Taylor, R. C., Cullen, S. P. & Martin, S. J. Apoptosis: controlled demolition at the cellular level. Nat. Rev. Mol. Cell Biol. 9, 231–241 (2008).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 21.

    Caruso, S. & Poon, I. K. H. Apoptotic cell-derived extracellular vesicles: more than just debris. Front Immunol. 9, 1486 (2018).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  • 22.

    Chen, H. et al. Extracellular vesicles from apoptotic cells promote TGFbeta production in macrophages and suppress experimental colitis. Sci. Rep. 9, 5875 (2019).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  • 23.

    Laing, A. G., Riffo-Vasquez, Y., Sharif-Paghaleh, E., Lombardi, G. & Sharpe, P. T. Immune modulation by apoptotic dental pulp stem cells in vivo. Immunotherapy 10, 201–211 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 24.

    Kou, X. et al. The Fas/Fap-1/Cav-1 complex regulates IL-1RA secretion in mesenchymal stem cells to accelerate wound healing. Sci. Transl. Med. 10, eaai8524 (2018).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  • 25.

    Zernecke, A. et al. Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci. Signal 2, ra81 (2009).

    PubMed  Article  PubMed Central  Google Scholar 

  • 26.

    Liu, J. et al. Apoptotic bodies derived from mesenchymal stem cells promote cutaneous wound healing via regulating the functions of macrophages. Stem Cell Res. Ther. 11, 507 (2020).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 27.

    Liu, Y. et al. Mesenchymal stem cell-based tissue regeneration is governed by recipient T lymphocytes via IFN-gamma and TNF-alpha. Nat. Med. 17, 1594–1601 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 28.

    Liu, S. et al. Mesenchymal stem cells prevent hypertrophic scar formation via inflammatory regulation when undergoing apoptosis. J. Invest. Dermatol. 134, 2648–2657 (2014).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 29.

    Galleu, A. et al. Apoptosis in mesenchymal stromal cells induces in vivo recipient-mediated immunomodulation. Sci. Transl. Med. 9, eaam7828 (2017).

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  • 30.

    Liu, H. et al. Donor MSCs release apoptotic bodies to improve myocardial infarction via autophagy regulation in recipient cells. Autophagy 16, 2140–2155 (2020).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 31.

    Chang, C. L. et al. Impact of apoptotic adipose-derived mesenchymal stem cells on attenuating organ damage and reducing mortality in rat sepsis syndrome induced by cecal puncture and ligation. J. Transl. Med. 10, 244 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 32.

    Chen, H. H. et al. Additional benefit of combined therapy with melatonin and apoptotic adipose-derived mesenchymal stem cell against sepsis-induced kidney injury. J. Pineal. Res. 57, 16–32 (2014).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 33.

    Liu, D. et al. Circulating apoptotic bodies maintain mesenchymal stem cell homeostasis and ameliorate osteopenia via transferring multiple cellular factors. Cell Res. 28, 918–933 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 34.

    Dou, G. et al. Chimeric apoptotic bodies functionalized with natural membrane and modular delivery system for inflammation modulation. Sci. Adv. 6, eaba2987 (2020).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 35.

    Gronthos, S., Mankani, M., Brahim, J., Robey, P. G. & Shi, S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc. Natl Acad. Sci. USA 97, 13625–13630 (2000).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 36.

    Miura, M. et al. SHED: stem cells from human exfoliated deciduous teeth. Proc. Natl Acad. Sci. USA 100, 5807–5812 (2003).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 37.

    Seo, B.-M. et al. Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 364, 149–155 (2004).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 38.

    Weiss, M. L. & Troyer, D. L. Stem cells in the umbilical cord. Stem Cell Rev. 2, 155–162 (2006).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 39.

    Bi, Y. et al. Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche. Nat. Med. 13, 1219–1227 (2007).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 40.

    Zhang, Q. et al. Mesenchymal stem cells derived from human gingiva are capable of immunomodulatory functions and ameliorate inflammation-related tissue destruction in experimental colitis. J. Immunol. 183, 7787–7798 (2009).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 41.

    Zuk, P. A. et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 7, 211–228 (2001).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 42.

    Shi, S. & Gronthos, S. Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. J. Bone Min. Res. 18, 696–704 (2003).

    Article  Google Scholar 

  • 43.

    Crisan, M. et al. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3, 301–313 (2008).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 44.

    Feng, J., Mantesso, A., De Bari, C., Nishiyama, A. & Sharpe, P. T. Dual origin of mesenchymal stem cells contributing to organ growth and repair. Proc. Natl Acad. Sci. USA 108, 6503–6508 (2011).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 45.

    Achilleos, A. & Trainor, P. A. Neural crest stem cells: discovery, properties and potential for therapy. Cell Res. 22, 288–304 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 46.

    Kaukua, N. et al. Glial origin of mesenchymal stem cells in a tooth model system. Nature 513, 551–554 (2014).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 47.

    Di Nicola, M. et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99, 3838–3843 (2002).

    PubMed  Article  PubMed Central  Google Scholar 

  • 48.

    Le Blanc, K. et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 363, 1439–1441 (2004).

    PubMed  Article  PubMed Central  Google Scholar 

  • 49.

    Puissant, B. et al. Immunomodulatory effect of human adipose tissue-derived adult stem cells: comparison with bone marrow mesenchymal stem cells. Br. J. Haematol. 129, 118–129 (2005).

    PubMed  Article  PubMed Central  Google Scholar 

  • 50.

    Nauta, A. J. & Fibbe, W. E. Immunomodulatory properties of mesenchymal stromal cells. Blood 110, 3499–3506 (2007).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 51.

    Ren, G. et al. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell 2, 141–150 (2008).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 52.

    Yamaza, T. et al. Immunomodulatory properties of stem cells from human exfoliated deciduous teeth. Stem Cell Res. Ther. 1, 5 (2010).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  • 53.

    Boiret, N. et al. Characterization of nonexpanded mesenchymal progenitor cells from normal adult human bone marrow. Exp. Hematol. 33, 219–225 (2005).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 54.

    Kortesidis, A. et al. Stromal-derived factor-1 promotes the growth, survival, and development of human bone marrow stromal stem cells. Blood 105, 3793–3801 (2005).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 55.

    Aslan, H. et al. Osteogenic differentiation of noncultured immunoisolated bone marrow-derived CD105+ cells. Stem Cells 24, 1728–1737 (2006).

    PubMed  Article  PubMed Central  Google Scholar 

  • 56.

    Lv, F. J., Tuan, R. S., Cheung, K. M. & Leung, V. Y. Concise review: the surface markers and identity of human mesenchymal stem cells. Stem Cells 32, 1408–1419 (2014).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 57.

    Zhao, H. et al. Secretion of shh by a neurovascular bundle niche supports mesenchymal stem cell homeostasis in the adult mouse incisor. Cell Stem Cell 14, 160–173 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 58.

    Vidovic, I. et al. alphaSMA-expressing perivascular cells represent dental pulp progenitors in vivo. J. Dent. Res. 96, 323–330 (2017).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 59.

    Lendahl, U., Zimmerman, L. B. & McKay, R. D. CNS stem cells express a new class of intermediate filament protein. Cell 60, 585–595 (1990).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 60.

    Zhou, B. O., Yue, R., Murphy, M. M., Peyer, J. G. & Morrison, S. J. Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow. Cell Stem Cell 15, 154–168 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 61.

    Liu, Y. et al. PD-1 is required to maintain stem cell properties in human dental pulp stem cells. Cell Death Differ. 25, 1350–1360 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 62.

    Galipeau, J. & Sensebe, L. Mesenchymal stromal cells: clinical challenges and therapeutic opportunities. Cell Stem Cell 22, 824–833 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 63.

    Chen, C. et al. Efficacy of umbilical cord-derived mesenchymal stem cell-based therapy for osteonecrosis of the femoral head: a three-year follow-up study. Mol. Med. Rep. 14, 4209–4215 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 64.

    Matas, J. et al. Umbilical cord-derived mesenchymal stromal cells (MSCs) for knee osteoarthritis: repeated MSC dosing is superior to a single MSC dose and to hyaluronic acid in a controlled randomized phase I/II trial. Stem Cells Transl. Med. 8, 215–224 (2019).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 65.

    Xuan, K. et al. Deciduous autologous tooth stem cells regenerate dental pulp after implantation into injured teeth. Sci. Transl. Med. 10, eaaf3227 (2018).

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  • 66.

    Kebriaei, P. et al. A phase 3 randomized study of remestemcel-L versus placebo added to second-line therapy in patients with steroid-refractory acute graft-versus-host disease. Biol. Blood Marrow Transpl. 26, 835–844 (2020).

    CAS  Article  Google Scholar 

  • 67.

    Yuan, X. et al. Mesenchymal stem cell therapy induces FLT3L and CD1c(+) dendritic cells in systemic lupus erythematosus patients. Nat. Commun. 10, 2498 (2019).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  • 68.

    Riordan, N. H. et al. Clinical feasibility of umbilical cord tissue-derived mesenchymal stem cells in the treatment of multiple sclerosis. J. Transl. Med. 16, 57 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 69.

    Williams, A. R. & Hare, J. M. Mesenchymal stem cells: biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease. Circ. Res. 109, 923–940 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 70.

    Kfoury, Y. & Scadden, D. T. Mesenchymal cell contributions to the stem cell niche. Cell Stem Cell 16, 239–253 (2015).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 71.

    Kim, S. G. et al. Dentin and dental pulp regeneration by the patient’s endogenous cells. Endod. Top. 28, 106–117 (2013).

    Article  Google Scholar 

  • 72.

    Gnecchi, M. et al. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat. Med. 11, 367–368 (2005).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 73.

    Gnecchi, M. et al. Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement. FASEB J. 20, 661–669 (2006).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 74.

    Kinnaird, T. et al. Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation 109, 1543–1549 (2004).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 75.

    Choi, H., Lee, R. H., Bazhanov, N., Oh, J. Y. & Prockop, D. J. Anti-inflammatory protein TSG-6 secreted by activated MSCs attenuates zymosan-induced mouse peritonitis by decreasing TLR2/NF-kappaB signaling in resident macrophages. Blood 118, 330–338 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 76.

    Ling, W. et al. Mesenchymal stem cells use IDO to regulate immunity in tumor microenvironment. Cancer Res. 74, 1576–1587 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 77.

    Wang, G. et al. Kynurenic acid, an IDO metabolite, controls TSG-6-mediated immunosuppression of human mesenchymal stem cells. Cell Death Differ. 25, 1209–1223 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 78.

    Aggarwal, S. & Pittenger, M. F. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105, 1815–1822 (2005).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 79.

    Du, L. et al. IGF-2 preprograms maturing macrophages to acquire oxidative phosphorylation-dependent anti-inflammatory properties. Cell Metab. 29, 1363–75 e8 (2019).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 80.

    Liu, S. et al. MSC transplantation improves osteopenia via epigenetic regulation of notch signaling in lupus. Cell Metab. 22, 606–618 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 81.

    Chen, C. et al. Mesenchymal stem cell transplantation in tight-skin mice identifies miR-151-5p as a therapeutic target for systemic sclerosis. Cell Res. 27, 559–577 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 82.

    Yang, R. et al. IFN-gamma promoted exosomes from mesenchymal stem cells to attenuate colitis via miR-125a and miR-125b. Cell Death Dis. 11, 603 (2020).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 83.

    Mayourian, J. et al. Exosomal microRNA-21-5p mediates mesenchymal stem cell paracrine effects on human cardiac tissue contractility. Circ. Res. 122, 933–944 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 84.

    Phinney, D. G. et al. Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs. Nat. Commun. 6, 8472 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 85.

    Fuchs, Y. & Steller, H. Live to die another way: modes of programmed cell death and the signals emanating from dying cells. Nat. Rev. Mol. Cell Biol. 16, 329–344 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 86.

    Doerflinger, M. et al. Flexible usage and interconnectivity of diverse cell death pathways protect against intracellular infection. Immunity 53, 533–47 e7 (2020).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  • 87.

    Zhang, Y., Chen, X., Gueydan, C. & Han, J. Plasma membrane changes during programmed cell deaths. Cell Res 28, 9–21 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 88.

    Coleman, M. L. et al. Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I. Nat. Cell Biol. 3, 339–345 (2001).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 89.

    Sisirak, V. et al. Digestion of chromatin in apoptotic cell microparticles prevents autoimmunity. Cell 166, 88–101 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 90.

    Cabral-Piccin, M. P. et al. Apoptotic CD8 T-lymphocytes disable macrophage-mediated immunity to Trypanosoma cruzi infection. Cell Death Dis. 7, e2232 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 91.

    Taylor, J. J., Pape, K. A., Steach, H. R. & Jenkins, M. K. Humoral immunity. Apoptosis and antigen affinity limit effector cell differentiation of a single naive B cell. Science 347, 784–787 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 92.

    Morris, A. B. et al. Signaling through the inhibitory Fc receptor FcgammaRIIB induces CD8(+) T cell apoptosis to limit T cell immunity. Immunity 52, 136–50 e6 (2020).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 93.

    Rodriguez-Manzanet, R. et al. T and B cell hyperactivity and autoimmunity associated with niche-specific defects in apoptotic body clearance in TIM-4-deficient mice. Proc. Natl Acad. Sci. USA 107, 8706–8711 (2010).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 94.

    Herrmann, M. et al. Impaired phagocytosis of apoptotic cell material by monocyte-derived macrophages from patients with systemic lupus erythematosus. Arthritis Rheum. 41, 1241–1250 (1998).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 95.

    Kawane, K. et al. Requirement of DNase II for definitive erythropoiesis in the mouse fetal liver. Science 292, 1546–1549 (2001).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 96.

    Kawane, K. et al. Chronic polyarthritis caused by mammalian DNA that escapes from degradation in macrophages. Nature 443, 998–1002 (2006).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 97.

    Berda-Haddad, Y. et al. Sterile inflammation of endothelial cell-derived apoptotic bodies is mediated by interleukin-1alpha. Proc. Natl Acad. Sci. USA 108, 20684–20689 (2011).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 98.

    Wickman, G. R. et al. Blebs produced by actin-myosin contraction during apoptosis release damage-associated molecular pattern proteins before secondary necrosis occurs. Cell Death Differ. 20, 1293–1305 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 99.

    Fogarty, C. E. & Bergmann, A. Killers creating new life: caspases drive apoptosis-induced proliferation in tissue repair and disease. Cell Death Differ. 24, 1390–1400 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 100.

    Chera, S. et al. Apoptotic cells provide an unexpected source of Wnt3 signaling to drive hydra head regeneration. Dev. Cell 17, 279–289 (2009).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 101.

    Gupta, K. H. et al. Apoptosis and compensatory proliferation signaling are coupled by CrkI-containing microvesicles. Dev. Cell 41, 674–84 e5 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 102.

    Brock, C. K. et al. Stem cell proliferation is induced by apoptotic bodies from dying cells during epithelial tissue maintenance. Nat. Commun. 10, 1044 (2019).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  • 103.

    Koren, E. et al. ARTS mediates apoptosis and regeneration of the intestinal stem cell niche. Nat. Commun. 9, 4582 (2018).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  • 104.

    Iimuro, Y. et al. NFkappaB prevents apoptosis and liver dysfunction during liver regeneration. J. Clin. Invest 101, 802–811 (1998).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 105.

    Malato, Y. et al. NF-kappaB essential modifier is required for hepatocyte proliferation and the oval cell reaction after partial hepatectomy in mice. Gastroenterology 143, 1597–608 e11 (2012).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 106.

    Neumann, B. et al. EFF-1-mediated regenerative axonal fusion requires components of the apoptotic pathway. Nature 517, 219–222 (2015).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 107.

    Perez-Garijo, A., Fuchs, Y. & Steller, H. Apoptotic cells can induce non-autonomous apoptosis through the TNF pathway. Elife 2, e01004 (2013).

    PubMed  PubMed Central  Article  Google Scholar 

  • 108.

    Li, Y. & Lin, F. Mesenchymal stem cells are injured by complement after their contact with serum. Blood 120, 3436–3443 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 109.

    Akiyama, K. et al. Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis. Cell Stem Cell 10, 544–555 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 110.

    Catalano, M. & O’Driscoll, L. Inhibiting extracellular vesicles formation and release: a review of EV inhibitors. J. Extracell. Vesicles 9, 1703244 (2020).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 111.

    Park, S. J. et al. Molecular mechanisms of biogenesis of apoptotic exosome-like vesicles and their roles as damage-associated molecular patterns. Proc. Natl Acad. Sci. USA 115, E11721–E11730 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 112.

    Atkin-Smith, G. K. et al. A novel mechanism of generating extracellular vesicles during apoptosis via a beads-on-a-string membrane structure. Nat. Commun. 6, 7439 (2015).

    PubMed  PubMed Central  Article  Google Scholar 

  • 113.

    Poon, I. K. et al. Unexpected link between an antibiotic, pannexin channels and apoptosis. Nature 507, 329–334 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 114.

    Poon, I. K. H. et al. Moving beyond size and phosphatidylserine exposure: evidence for a diversity of apoptotic cell-derived extracellular vesicles in vitro. J. Extracell. Vesicles 8, 1608786 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 115.

    Lleo, A. et al. Shotgun proteomics: identification of unique protein profiles of apoptotic bodies from biliary epithelial cells. Hepatology 60, 1314–1323 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 116.

    Dieude, M. et al. The 20S proteasome core, active within apoptotic exosome-like vesicles, induces autoantibody production and accelerates rejection. Sci. Transl. Med. 7, 318ra200 (2015).

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  • 117.

    Xie, Y. et al. Tumor apoptotic bodies inhibit CTL responses and antitumor immunity via membrane-bound transforming growth factor-beta1 inducing CD8+ T-cell anergy and CD4+ Tr1 cell responses. Cancer Res. 69, 7756–7766 (2009).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • 118.

    Frleta, D. et al. HIV-1 infection-induced apoptotic microparticles inhibit human DCs via CD44. J. Clin. Invest 122, 4685–4697 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 119.

    Ma, Y. et al. Autophagy controls mesenchymal stem cell properties and senescence during bone aging. Aging Cell 17, e12709 (2018).

    Article  CAS  Google Scholar 

  • 120.

    Cen, S. et al. Autophagy enhances mesenchymal stem cell-mediated CD4(+) T cell migration and differentiation through CXCL8 and TGF-beta1. Stem Cell Res. Ther. 10, 265 (2019).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  • 121.

    Regmi, S. et al. Enhanced viability and function of mesenchymal stromal cell spheroids is mediated via autophagy induction. Autophagy 2020: 1−20.

  • 122.

    Chen, Y. et al. Mesenchymal stromal cells directly promote inflammation by canonical NLRP3 and non-canonical caspase-11 inflammasomes. EBioMedicine 32, 31–42 (2018).

    PubMed  PubMed Central  Article  Google Scholar 

  • 123.

    Pasparakis, M. & Vandenabeele, P. Necroptosis and its role in inflammation. Nature 517, 311–320 (2015).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • Read original article here.