Skip to main content

Advertisement

SpringerLink
Log in

Cross Talk between Mesenchymal Stem/Stromal Cells and Innate Immunocytes Concerning Lupus Disease

  • Published:
Stem Cell Reviews and Reports Aims and scope Submit manuscript

Abstract

Lupus is known as a systemic immune-mediated disorder. Like other diseases in this category, its cause and definitive treatment remain unknown. Gold standard therapies, which mainly include immunosuppressive agents, have been able to have therapeutic effects on patients. However, a significant percentage of cases still do not respond to this kind of treatment, resulting in death from complications. Recently, a new source of non-hematopoietic cells, mesenchymal stem/stromal cells (MSCs), with the potency to re-establishment immune homeostasis and tissue regeneration, has been wildly used in both primary and clinical research. One of the remarkable features of MSCs is their anti-inflammatory and immunosuppressive properties and stimulating tissue differentiation programs. Under the influence of background signals, MSCs migrate to inflammatory bioactive substances and then regulate overactive immune responses to restore immune tolerance. MSCs have shown a two-way interaction with most immunocytes, which plays a significant role in resolving sterile inflammation. Restricting the entry of inflamed cells into the site of inflammation and re-educated infiltrated cells to achieve a tolerant phenotype have been reported as mechanisms of MSCs in tissue repair. Stimulation of the endogenous and tissue-dwelling stem cells in addition to releasing immunomodulatory agents, suggests MSCs transplantation as a potential modality in the treatment of future immune-mediated disorders.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data Availability

There is no data to share because the article is a review.

Abbreviations

AD:

Adipose-derived

BAX:

Bcl-2-associated X protein

Bcl-2:

Bcell lymphoma 2

BM:

Bone marrow

C3aR:

C3a receptor

C5aR:

C5a receptor

CCL19:

chemokine (C-C motif) ligand 19

CCR7:

C-Cchemokine receptor 7

DC:

Dendritic cell

dsDNA:

Double strand DNA

FH:

Factor H

HLA-G5:

Human leukocyte antigen-G5

HSC:

Hematopoietic stem cells

ICAM-1:

Intercellular adhesion molecule1

IDO:

Indoleamine 2, 3-dioxygenase

IFN-γ:

Interferon gamma

IL:

Interleukin

IM:

Intramuscular

IP:

Intraperitoneal

IV:

Intravascular

LN:

Lupus nephritis

MBL:

Mannose-binding lectin

MHC:

Major histocompatibility complex

MSC:

Mesenchymal stem cell

MQ:

Macrophage

NEU:

Neutrophil

NK:

Natural killer

PGE2:

Prostaglandin E2

PMN:

Polymorphonuclear

SLE:

Systemic lupus erythematosus

T cell:

T helper cell

TGF-β:

Transforming growth factor beta

TNF-α:

Tumor necrosis factor alpha

Treg:

T regulatory cell

TSG-6:

Tumour necrosis factor-stimulated gene 6 protein

UC:

Umbilical cord

VCAM-1:

Vascular cell adhesion molecule 1

References

  1. Klein, A., Polliack, A., & Gafter-Gvili, A. (2018). Systemic lupus erythematosus and lymphoma: Incidence, pathogenesis and biology. Leukemia Research, 75, 45–49.

    Article  CAS  PubMed  Google Scholar 

  2. Yeoh, S.-A., Dias, S. S., & Isenberg, D. A. (2018). Advances in systemic lupus erythematosus. Medicine, 46(2), 84–92.

    Article  Google Scholar 

  3. Turksen, K. (2020). Cell biology and translational medicine, Vol. 9. In Stem Cell-Based Therapeutic Approaches in Disease, Vol. 1288. Springer Nature.

  4. Potdar, P., & Deshpande, S. (2013). Mesenchymal stem cell transplantation: New, avenues for stem cell therapies. The Journal of Transplantation Technologies & Research, 3(122), 2161–0991 1000122.

    Google Scholar 

  5. Yan, S., et al. (2014). MicroRNA regulation in systemic lupus erythematosus pathogenesis. Immune Network, 14(3), 138–148.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Zan, H., Tat, C., & Casali, P. (2014). MicroRNAs in lupus. Autoimmunity, 47(4), 272–285.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Fava, A., & Petri, M. (2019). Systemic lupus erythematosus: Diagnosis and clinical management. Journal of Autoimmunity, 96, 1–13.

    Article  PubMed  Google Scholar 

  8. Gatto, M., et al. (2019). New therapeutic strategies in systemic lupus erythematosus management. Nature Reviews Rheumatology, 15(1), 30–48.

    Article  CAS  PubMed  Google Scholar 

  9. Kuhn, A., et al. (2015). The diagnosis and treatment of systemic lupus erythematosus. Deutsches Ärzteblatt International, 112(25), 423.

    PubMed  PubMed Central  Google Scholar 

  10. Cras, A., et al. (2015). Update on mesenchymal stem cell-based therapy in lupus and scleroderma. Arthritis Research & Therapy, 17(1), 1–9.

    Article  Google Scholar 

  11. Wang, D., & Sun, L. (2019). Chapter 7 - systemic lupus erythematosus. In X.-D. Chen (Ed.), A roadmap to non-hematopoietic stem cell-based therapeutics (pp. 143–172). Academic Press.

    Chapter  Google Scholar 

  12. Marmont, A., et al. (1997). Autologous marrow stem cell transplantation for severe systemic lupus erythematosus of long duration. Lupus, 6(6), 545–548.

    Article  CAS  PubMed  Google Scholar 

  13. Caplan, A. I. (1991). Mesenchymal stem cells. Journal of Orthopaedic Research, 9(5), 641–650.

    Article  CAS  PubMed  Google Scholar 

  14. Le Blanc, K., et al. (2008). Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: A phase II study. The Lancet, 371(9624), 1579–1586.

    Article  Google Scholar 

  15. Nauta, A. J., & Fibbe, W. E. (2007). Immunomodulatory properties of mesenchymal stromal cells. Blood, The Journal of the American Society of Hematology, 110(10), 3499–3506.

    CAS  Google Scholar 

  16. Arribas, M. I., et al. (2012). Adipose cell-derived stem cells: Neurogenic and immunomodulatory potentials. Advances in Neuroimmune Biology, 3(1), 19–30.

    Article  Google Scholar 

  17. Luz-Crawford, P., et al. (2019). Mesenchymal stem cell repression of Th17 cells is triggered by mitochondrial transfer. Stem Cell Research & Therapy, 10(1), 1–13.

    Article  CAS  Google Scholar 

  18. Wang, D., et al. (2011). Effect of allogeneic bone marrow–derived mesenchymal stem cells transplantation in a polyI: C-induced primary biliary cirrhosis mouse model. Clinical and Experimental Medicine, 11(1), 25–32.

    Article  CAS  PubMed  Google Scholar 

  19. Wang, M., et al. (2016). Intraperitoneal injection (IP), intravenous injection (IV) or anal injection (AI)? Best way for mesenchymal stem cells transplantation for colitis. Scientific Reports, 6, 30696.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Krampera, M., et al. (2006). Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells, 24(2), 386–398.

    Article  CAS  PubMed  Google Scholar 

  21. Liotta, F., et al. (2008). Toll-like receptors 3 and 4 are expressed by human bone marrow-derived mesenchymal stem cells and can inhibit their T-cell modulatory activity by impairing notch signaling. Stem Cells, 26(1), 279–289.

    Article  CAS  PubMed  Google Scholar 

  22. Somoza, R., Correa, D., & Caplan, A. (2016). Roles for mesenchymal stem cells as medicinal signaling cells. Nature Protocols, 11.

  23. Kunisaki, Y., et al. (2013). Arteriolar niches maintain haematopoietic stem cell quiescence. Nature, 502(7473), 637–643.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. D, S.d.B, Casamitjana, J., & Crisan, M. (2017). Pericytes, integral components of adult hematopoietic stem cell niches. Pharmacology & Therapeutics, 171, 104–113.

    Article  Google Scholar 

  25. Caplan, A. I. (2017). Mesenchymal stem cells: Time to change the name! Stem Cells Translational Medicine, 6(6), 1445–1451.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Sala, E., et al. (2015). Mesenchymal stem cells reduce colitis in mice via release of TSG6, independently of their localization to the intestine. Gastroenterology, 149(1), 163–176.e20.

    Article  CAS  PubMed  Google Scholar 

  27. Lee, R. H., et al. (2009). 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(1), 54–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Caplan, A. I., & Correa, D. (2011). The MSC: An injury drugstore. Cell Stem Cell, 9(1), 11–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kabat, M., et al. (2020). Trends in mesenchymal stem cell clinical trials 2004-2018: Is efficacy optimal in a narrow dose range? Stem Cells Translational Medicine, 9(1), 17–27.

    Article  CAS  PubMed  Google Scholar 

  30. Moll, G., et al. (2019). Intravascular mesenchymal stromal/stem cell therapy product diversification: Time for new clinical guidelines. Trends in Molecular Medicine, 25(2), 149–163.

    Article  PubMed  Google Scholar 

  31. Braid, L. R., et al. (2018). Intramuscular administration potentiates extended dwell time of mesenchymal stromal cells compared to other routes. Cytotherapy, 20(2), 232–244.

    Article  PubMed  Google Scholar 

  32. Han, J. W., et al. (2016). Bone marrow-derived mesenchymal stem cells improve diabetic neuropathy by direct modulation of both angiogenesis and myelination in peripheral nerves. Cell Transplantation, 25(2), 313–326.

    Article  PubMed  Google Scholar 

  33. Francki, A., et al. (2016). Angiogenic properties of human placenta-derived adherent cells and efficacy in hindlimb ischemia. Journal of Vascular Surgery, 64(3), 746–756 e1.

    Article  PubMed  Google Scholar 

  34. Lee, H.-B., et al. (2019). Intramuscular Injection of Adipose Tissue Derived Stromal Vascular Fraction in Subjects with Poliomyelitis: Case Reports. International Journal of Stem Cell Research & Therapeutics, 1(1), 20–27.

    Google Scholar 

  35. Soria-Juan, B., et al. (2021). Efficacy and safety of intramuscular administration of allogeneic adipose tissue derived and expanded mesenchymal stromal cells in patients with critical limb ischemia and type 2 diabetes with no possibility of revascularization: Study protocol for a randomized controlled double-blind phase II clinical trial (The NOMA Trial). Trials, 22(1), 595.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Wu, S. C., et al. (2017). Safety and efficacy of intramuscular human placenta-derived mesenchymal stromal-like cells (cenplacel [PDA-002]) in patients who have a diabetic foot ulcer with peripheral arterial disease. International Wound Journal, 14(5), 823–829.

    Article  PubMed  PubMed Central  Google Scholar 

  37. van Rhijn-Brouwer, F. C., et al. (2018). A randomised placebo-controlled double-blind trial to assess the safety of intramuscular administration of allogeneic mesenchymal stromal cells for digital ulcers in systemic sclerosis: The MANUS trial protocol. BMJ Open, 8(8), e020479.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Youd, M., et al. (2010). Allogeneic mesenchymal stem cells do not protect NZB× NZW F1 mice from developing lupus disease. Clinical and Experimental Immunology, 161(1), 176–186.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Sun, L., et al. (2014). Bone mesenchymal stem cell transplantation via four routes for the treatment of acute liver failure in rats. International Journal of Molecular Medicine, 34(4), 987–996.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Oh, J. Y., et al. (2014). Intraperitoneal infusion of mesenchymal stem/stromal cells prevents experimental autoimmune uveitis in mice. Mediators of Inflammation, 2014.

  41. Nam, Y., et al. (2018). Intraperitoneal infusion of mesenchymal stem cell attenuates severity of collagen antibody induced arthritis. PLoS One, 13(6), e0198740.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Wang, M., et al. (2016). Intraperitoneal injection (IP), intravenous injection (IV) or anal injection (AI)? Best way for mesenchymal stem cells transplantation for colitis. Scientific Reports, 6(1), 1–13.

    Google Scholar 

  43. da Costa Gonçalves, F., et al. (2014). Intravenous vs intraperitoneal mesenchymal stem cells administration: What is the best route for treating experimental colitis? World Journal of Gastroenterology: WJG, 20(48), 18228.

    Article  Google Scholar 

  44. Petrou, P., et al. (2016). Safety and clinical effects of mesenchymal stem cells secreting neurotrophic factor transplantation in patients with amyotrophic lateral sclerosis: Results of phase 1/2 and 2a clinical trials. JAMA Neurology, 73(3), 337–344.

    Article  PubMed  Google Scholar 

  45. Bartholomew, A., et al. (2002). Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Experimental Hematology, 30(1), 42–48.

    Article  PubMed  Google Scholar 

  46. Figueroa, F. E., et al. (2012). Mesenchymal stem cell treatment for autoimmune diseases: A critical review. Biological Research, 45(3), 269–277.

    Article  PubMed  Google Scholar 

  47. Marigo, I., & Dazzi, F. The immunomodulatory properties of mesenchymal stem cells. In seminars in immunopathology. 2011. Springer.

  48. Shi, Y., et al. (2012). How mesenchymal stem cells interact with tissue immune responses. Trends in Immunology, 33(3), 136–143.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Carrion, F. A., & Figueroa, F. E. (2011). Mesenchymal stem cells for the treatment of systemic lupus erythematosus: Is the cure for connective tissue diseases within connective tissue? Stem Cell Research & Therapy, 2(3), 23.

    Article  Google Scholar 

  50. Bosi, C., Lanzoni, G., & Pugliese, A. (2016). Clinical trials of mesenchymal stem cell transplantation in patients with type 1 diabetes and systemic lupus erythematosus: Is it time for larger studies. CellR4, 4(5), e2134.

    Google Scholar 

  51. Wen, L., et al. (2019). Prognostic factors for clinical response in systemic lupus erythematosus patients treated by allogeneic mesenchymal stem cells. Stem Cells International, 2019, 7061408.

  52. Zhu, Y., & Feng, X. (2018). Genetic contribution to mesenchymal stem cell dysfunction in systemic lupus erythematosus. Stem Cell Research & Therapy, 9(1), 1–6.

    Article  Google Scholar 

  53. Brandau, S., et al. (2010). Tissue-resident mesenchymal stem cells attract peripheral blood neutrophils and enhance their inflammatory activity in response to microbial challenge. Journal of Leukocyte Biology, 88(5), 1005–1015.

    Article  CAS  PubMed  Google Scholar 

  54. Taghavi-Farahabadi, M., et al. (2020). Immunological Investigations, 1–16.

  55. Maqbool, M., et al. (2011). Human mesenchymal stem cells protect neutrophils from serum-deprived cell death. Cell Biology International, 35(12), 1247–1251.

    Article  CAS  PubMed  Google Scholar 

  56. Mittal, S. K., et al. (2018). Mesenchymal stromal cells inhibit neutrophil effector functions in a murine model of ocular inflammation. Investigative Ophthalmology & Visual Science, 59(3), 1191–1198.

    Article  CAS  Google Scholar 

  57. Hall, S. R., et al. (2013). Mesenchymal stromal cells improve survival during sepsis in the absence of heme oxygenase-1: The importance of neutrophils. Stem Cells, 31(2), 397–407.

    Article  CAS  PubMed  Google Scholar 

  58. Le Blanc, K., & Mougiakakos, D. (2012). Multipotent mesenchymal stromal cells and the innate immune system. Nature Reviews. Immunology, 12(5), 383–396.

    Article  PubMed  Google Scholar 

  59. Munir, H., et al. (2016). Comparative ability of mesenchymal stromal cells from different tissues to limit neutrophil recruitment to inflamed endothelium. PLoS One, 11(5), e0155161.

    Article  PubMed  PubMed Central  Google Scholar 

  60. English, K. (2013). Mechanisms of mesenchymal stromal cell immunomodulation. Immunology and Cell Biology, 91(1), 19–26.

    Article  CAS  PubMed  Google Scholar 

  61. Cai, B., et al. (2021). N2-polarized neutrophils guide bone mesenchymal stem cell recruitment and initiate bone regeneration: A missing piece of the bone regeneration puzzle. Advanced Science, 8(19), 2100584.

    Article  CAS  PubMed Central  Google Scholar 

  62. Hu, X., et al. (2014). Programming of the development of tumor-promoting neutrophils by mesenchymal stromal cells. Cellular Physiology and Biochemistry, 33(6), 1802–1814.

    Article  CAS  PubMed  Google Scholar 

  63. Raffaghello, L., et al. (2008). Human mesenchymal stem cells inhibit neutrophil apoptosis: A model for neutrophil preservation in the bone marrow niche. Stem Cells, 26(1), 151–162.

    Article  CAS  PubMed  Google Scholar 

  64. Zhao, J., et al. (2019). Mesenchymal stromal cell-derived exosomes attenuate myocardial ischaemia-reperfusion injury through miR-182-regulated macrophage polarization. Cardiovascular Research, 115(7), 1205–1216.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Nakajima, H., et al. (2012). Transplantation of mesenchymal stem cells promotes an alternative pathway of macrophage activation and functional recovery after spinal cord injury. Journal of Neurotrauma, 29(8), 1614–1625.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Anderson, P., et al. (2013). Adipose-derived mesenchymal stromal cells induce immunomodulatory macrophages which protect from experimental colitis and sepsis. Gut, 62(8), 1131–1141.

    Article  CAS  PubMed  Google Scholar 

  67. Zhang, Z., et al. (2018). Mesenchymal stem cells prevent podocyte injury in lupus-prone B6.MRL-Faslpr mice via polarizing macrophage into an anti-inflammatory phenotype. Nephrology, Dialysis, Transplantation, 33(11), 2069–2069.

    Article  PubMed  Google Scholar 

  68. Braza, F., et al. (2016). Mesenchymal stem cells induce suppressive macrophages through phagocytosis in a mouse model of asthma. Stem Cells, 34(7), 1836–1845.

    Article  CAS  PubMed  Google Scholar 

  69. Liu, Y., et al. (2018). AMSC-derived exosomes alleviate lipopolysaccharide/d-galactosamine-induced acute liver failure by miR-17-mediated reduction of TXNIP/NLRP3 inflammasome activation in macrophages. EBioMedicine, 36, 140–150.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Kim, J., & Hematti, P. (2009). Mesenchymal stem cell-educated macrophages: A novel type of alternatively activated macrophages. Experimental Hematology, 37(12), 1445–1453.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Eggenhofer, E., & Hoogduijn, M. J. (2012). Mesenchymal stem cell-educated macrophages. Transplantation Research, 1(1), 12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Takizawa, N., et al. (2017). Bone marrow-derived mesenchymal stem cells propagate immunosuppressive/anti-inflammatory macrophages in cell-to-cell contact-independent and-dependent manners under hypoxic culture. Experimental Cell Research, 358(2), 411–420.

    Article  CAS  PubMed  Google Scholar 

  73. Tang, X.-D., et al. (2017). Mesenchymal stem cell microvesicles attenuate acute lung injury in mice partly mediated by Ang-1 mRNA. Stem Cells, 35(7), 1849–1859.

    Article  CAS  PubMed  Google Scholar 

  74. Hidalgo-Garcia, L., et al. (2018). Can a conversation between mesenchymal stromal cells and macrophages solve the crisis in the inflamed intestine? Frontiers in Pharmacology, 9, 179.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Morrison, T. J., et al. (2017). Mesenchymal stromal cells modulate macrophages in clinically relevant lung injury models by extracellular vesicle mitochondrial transfer. American Journal of Respiratory and Critical Care Medicine, 196(10), 1275–1286.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Lopez-Santalla, M., et al. (2020). Cell therapy with mesenchymal stem cells induces an innate immune memory response that attenuates experimental colitis in the long term. Journal of Crohn's and Colitis, 14(10), 1424–1435.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Spaggiari, G. M., et al. (2006). Mesenchymal stem cell-natural killer cell interactions: Evidence that activated NK cells are capable of killing MSCs, whereas MSCs can inhibit IL-2-induced NK-cell proliferation. Blood, 107(4), 1484–1490.

    Article  CAS  PubMed  Google Scholar 

  78. Sotiropoulou, P. A., et al. (2006). Interactions between human mesenchymal stem cells and natural killer cells. Stem Cells, 24(1), 74–85.

    Article  PubMed  Google Scholar 

  79. Fan, Y., et al. (2019). Human fetal liver mesenchymal stem cell-derived Exosomes impair natural killer cell function. Stem Cells and Development, 28(1), 44–55.

    Article  CAS  PubMed  Google Scholar 

  80. Spaggiari, G. M., & Moretta, L. (2012). Mesenchymal stem cell-natural killer cell interactions. In Stem cells and Cancer stem cells (Vol. Volume 4, pp. 217–224). Springer.

    Chapter  Google Scholar 

  81. Galland, S., et al. (2017). Tumor-derived mesenchymal stem cells use distinct mechanisms to block the activity of natural killer cell subsets. Cell Reports, 20(12), 2891–2905.

    Article  CAS  PubMed  Google Scholar 

  82. Spaggiari, G. M., & Moretta, L. (2013). Cellular and molecular interactions of mesenchymal stem cells in innate immunity. Immunology and Cell Biology, 91(1), 27–31.

    Article  CAS  PubMed  Google Scholar 

  83. Bruno, S., Deregibus, M. C., & Camussi, G. (2015). The secretome of mesenchymal stromal cells: Role of extracellular vesicles in immunomodulation. Immunology Letters, 168(2), 154–158.

    Article  CAS  PubMed  Google Scholar 

  84. Petri, R. M., et al. (2017). Activated tissue-resident mesenchymal stromal cells regulate natural killer cell immune and tissue-regenerative function. Stem Cell Reports, 9(3), 985–998.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Deng, Y., et al. (2014). Umbilical cord-derived mesenchymal stem cells instruct dendritic cells to acquire tolerogenic phenotypes through the IL-6-mediated upregulation of SOCS1. Stem Cells and Development, 23(17), 2080–2092.

    Article  CAS  PubMed  Google Scholar 

  86. Radmanesh, F., et al. (2020). The immunomodulatory effects of mesenchymal stromal cell-based therapy in human and animal models of systemic lupus erythematosus. IUBMB Life, 72(11), 2366–2381.

    Article  CAS  PubMed  Google Scholar 

  87. Chen, P., Huang, Y., & Womer, K. L. (2015). Effects of mesenchymal stromal cells on human myeloid dendritic cell differentiation and maturation in a humanized mouse model. Journal of Immunological Methods, 427, 100–104.

    Article  CAS  PubMed  Google Scholar 

  88. Spaggiari, G. M., et al. (2009). MSCs inhibit monocyte-derived DC maturation and function by selectively interfering with the generation of immature DCs: Central role of MSC-derived prostaglandin E2. Blood, The Journal of the American Society of Hematology, 113(26), 6576–6583.

    CAS  Google Scholar 

  89. Djokic, J., Tomic, S., & Čolić, M. (2015). Cross-talk between mesenchymal stem/stromal cells and dendritic cells. Current Stem Cell Research & Therapy.

  90. Chiesa, S., et al. (2011). Mesenchymal stem cells impair in vivo T-cell priming by dendritic cells. Proceedings of the National Academy of Sciences, 108(42), 17384–17389.

    Article  CAS  Google Scholar 

  91. Liu, X., et al. (2012). Mesenchymal stem/stromal cells induce the generation of novel IL-10–dependent regulatory dendritic cells by SOCS3 activation. The Journal of Immunology, 189(3), 1182–1192.

    Article  CAS  PubMed  Google Scholar 

  92. Zhao, Z. G., et al. (2012). The characteristics and immunoregulatory functions of regulatory dendritic cells induced by mesenchymal stem cells derived from bone marrow of patient with chronic myeloid leukaemia. European Journal of Cancer, 48(12), 1884–1895.

    Article  CAS  PubMed  Google Scholar 

  93. Zhang, B., et al. (2009). Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2–dependent regulatory dendritic cell population. Blood, The Journal of the American Society of Hematology, 113(1), 46–57.

    CAS  Google Scholar 

  94. Lu, Z., et al. (2019). Mesenchymal stem cells induce dendritic cell immune tolerance via paracrine hepatocyte growth factor to alleviate acute lung injury. Stem Cell Research & Therapy, 10(1), 1–16.

    Article  Google Scholar 

  95. Beyth, S., et al. (2005). Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness. Blood, 105(5), 2214–2219.

    Article  CAS  PubMed  Google Scholar 

  96. Dokić, J., et al. (2013). Mesenchymal stem cells from periapical lesions modulate differentiation and functional properties of monocyte-derived dendritic cells. European Journal of Immunology, 43(7), 1862–1872.

    Article  PubMed  Google Scholar 

  97. Obermajer, N., et al. (2011). Positive feedback between PGE2 and COX2 redirects the differentiation of human dendritic cells toward stable myeloid-derived suppressor cells. Blood, 118(20), 5498–5505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Liu, Y., et al. (2014). MSCs inhibit bone marrow-derived DC maturation and function through the release of TSG-6. Biochemical and Biophysical Research Communications, 450(4), 1409–1415.

    Article  CAS  PubMed  Google Scholar 

  99. Li, Y. P., et al. (2008). Human mesenchymal stem cells license adult CD34+ hemopoietic progenitor cells to differentiate into regulatory dendritic cells through activation of the notch pathway. Journal of Immunology, 180(3), 1598–1608.

    Article  CAS  Google Scholar 

  100. de Witte, S. F. H., et al. (2018). Immunomodulation by therapeutic mesenchymal stromal cells (MSC) is triggered through phagocytosis of MSC by Monocytic cells. Stem Cells, 36(4), 602–615.

    Article  PubMed  Google Scholar 

  101. Wynn, T. A., Chawla, A., & Pollard, J. W. (2013). Macrophage biology in development, homeostasis and disease. Nature, 496(7446), 445–455.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Wynn, T. A., & Vannella, K. M. (2016). Macrophages in tissue repair, regeneration, and fibrosis. Immunity, 44(3), 450–462.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Deng, Y., et al. (2016). Umbilical cord-derived mesenchymal stem cells instruct monocytes towards an IL10-producing phenotype by secreting IL6 and HGF. Scientific Reports, 6(1), 1–9.

    Article  Google Scholar 

  104. Selleri, S., et al. (2016). Human mesenchymal stromal cell-secreted lactate induces M2-macrophage differentiation by metabolic reprogramming. Oncotarget, 7(21), 30193.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Giri, J., et al. (2020). CCL2 and CXCL12 derived from mesenchymal stromal cells cooperatively polarize IL-10+ tissue macrophages to mitigate gut injury. Cell Reports, 30(6), 1923–1934 e4.

    Article  CAS  PubMed  Google Scholar 

  106. McDonald, B., et al. (2010). Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science, 330(6002), 362–366.

    Article  CAS  PubMed  Google Scholar 

  107. Mahmoudi, M., et al. (2019). Comparison of the effects of adipose tissue mesenchymal stromal cell-derived exosomes with conditioned media on neutrophil function and apoptosis. International Immunopharmacology, 74, 105689.

    Article  CAS  PubMed  Google Scholar 

  108. Kwon, M.-Y., et al. (2020). Expression of stromal cell-derived factor-1 by mesenchymal stromal cells impacts neutrophil function during sepsis. Critical Care Medicine, 48(5), e409.

    Article  CAS  PubMed  Google Scholar 

  109. Steinman, R. M., Hawiger, D., & Nussenzweig, M. C. (2003). Tolerogenic dendritic cells. Annual Review of Immunology, 21(1), 685–711.

    Article  CAS  PubMed  Google Scholar 

  110. Yuan, X., et al. (2019). Mesenchymal stem cell therapy induces FLT3L and CD1c(+) dendritic cells in systemic lupus erythematosus patients. Nature Communications, 10(1), 2498.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Aldinucci, A., et al. (2010). Inhibition of immune synapse by altered dendritic cell actin distribution: A new pathway of mesenchymal stem cell immune regulation. Journal of Immunology, 185(9), 5102–5110.

    Article  CAS  Google Scholar 

  112. Agaugué, S., et al. (2008). Human natural killer cells exposed to IL-2, IL-12, IL-18, or IL-4 differently modulate priming of naive T cells by monocyte-derived dendritic cells. Blood, 112(5), 1776–1783.

    Article  PubMed  Google Scholar 

  113. Moretta, L., et al. (2006). Effector and regulatory events during natural killer–dendritic cell interactions. Immunological Reviews, 214(1), 219–228.

    Article  CAS  PubMed  Google Scholar 

  114. Reinders, M. E., & Hoogduijn, M. J. (2014). NK cells and MSCs: Possible implications for MSC therapy in renal transplantation. Stem Cell Research & Therapy, 4(2), 1000166.

    Google Scholar 

  115. Schraufstatter, I. U., Khaldoyanidi, S. K., & DiScipio, R. G. (2015). Complement activation in the context of stem cells and tissue repair. World Journal of Stem Cells, 7(8), 1090–1108.

    Article  PubMed  PubMed Central  Google Scholar 

  116. Soland, M. A., et al. (2013). Mesenchymal stem cells engineered to inhibit complement-mediated damage. PLoS One, 8(3), e60461.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Salvadori, M., & Bertoni, E. (2016). Complement related kidney diseases: Recurrence after transplantation. World Journal of Transplantation, 6(4), 632–645.

    Article  PubMed  PubMed Central  Google Scholar 

  118. Sato, N., et al. (2011). Significance of glomerular activation of the alternative pathway and lectin pathway in lupus nephritis. Lupus, 20(13), 1378–1386.

    Article  CAS  PubMed  Google Scholar 

  119. Teixeira, J. E., et al. (1996). CR1 stump peptide and terminal complement complexes are found in the glomeruli of lupus nephritis patients. Clinical and Experimental Immunology, 105(3), 497–503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Arriens, C., et al. (2017). Systemic lupus erythematosus biomarkers: The challenging quest. Rheumatology (Oxford), 56(suppl_1), i32–i45.

    CAS  Google Scholar 

  121. Tan, Y., et al. (2013). Serum levels and renal deposition of C1q complement component and its antibodies reflect disease activity of lupus nephritis. BMC Nephrology, 14, 63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Botto, M., et al. (1998). Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nature Genetics, 19(1), 56–59.

    Article  CAS  PubMed  Google Scholar 

  123. Tu, Z., et al. (2010). Mesenchymal stem cells inhibit complement activation by secreting factor H. Stem Cells and Development, 19(11), 1803–1809.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Ma, H., et al. (2018). Mesenchymal stem cells control complement C5 activation by factor H in lupus nephritis. EBioMedicine, 32, 21–30.

    Article  PubMed  PubMed Central  Google Scholar 

  125. Moll, G., et al. (2011). Mesenchymal stromal cells engage complement and complement receptor bearing innate effector cells to modulate immune responses. PLoS One, 6(7), e21703.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Wang, F. M., et al. (2016). The dysfunctions of complement factor H in lupus nephritis. Lupus, 25(12), 1328–1340.

    Article  CAS  PubMed  Google Scholar 

  127. Stegert, M., Bock, M., & Trendelenburg, M. (2015). Clinical presentation of human C1q deficiency: How much of a lupus? Molecular Immunology, 67(1), 3–11.

    Article  CAS  PubMed  Google Scholar 

  128. Gavin, C., et al. (2019). The complement system is essential for the phagocytosis of mesenchymal stromal cells by monocytes. Frontiers in Immunology, 10, 2249.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Liang, J., & Sun, L. (2015). Mesenchymal stem cells transplantation for systemic lupus erythematosus. International Journal of Rheumatic Diseases, 18(2), 164–171.

    Article  PubMed  Google Scholar 

  130. Zhao, C., et al. (2019). Exosomes derived from bone marrow mesenchymal stem cells inhibit complement activation in rats with spinal cord injury. Drug Design, Development and Therapy, 13, 3693–3704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Nisihara, R. M., et al. (2013). Deposition of the lectin pathway of complement in renal biopsies of lupus nephritis patients. Human Immunology, 74(8), 907–910.

    Article  CAS  PubMed  Google Scholar 

  132. Sadanaga, A., et al. (2007). Protection against autoimmune nephritis in MyD88-deficient MRL/lpr mice. Arthritis and Rheumatism, 56(5), 1618–1628.

    Article  CAS  PubMed  Google Scholar 

  133. Ma, X., et al. (2013). Allogenic mesenchymal stem cell transplantation ameliorates nephritis in lupus mice via inhibition of B-cell activation. Cell Transplantation, 22(12), 2279–2290.

    Article  PubMed  Google Scholar 

  134. Deng, W., et al. (2005). Effects of allogeneic bone marrow-derived mesenchymal stem cells on T and B lymphocytes from BXSB mice. DNA and Cell Biology, 24(7), 458–463.

    Article  CAS  PubMed  Google Scholar 

  135. Wang, D., et al. (2013). Allogeneic mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus: 4 years of experience. Cell Transplantation, 22(12), 2267–2277.

    Article  PubMed  Google Scholar 

  136. Yang, X., et al. (2018). Bone marrow-derived mesenchymal stem cells inhibit T follicular helper cell in lupus-prone mice. Lupus, 27(1), 49–59.

    Article  CAS  PubMed  Google Scholar 

  137. Choi, E. W., et al. (2012). Reversal of serologic, immunologic, and histologic dysfunction in mice with systemic lupus erythematosus by long-term serial adipose tissue–derived mesenchymal stem cell transplantation. Arthritis and Rheumatism, 64(1), 243–253.

    Article  CAS  PubMed  Google Scholar 

  138. Park, M.-J., et al. (2015). Adipose tissue-derived mesenchymal stem cells induce expansion of interleukin-10-producing regulatory B cells and ameliorate autoimmunity in a murine model of systemic lupus erythematosus. Cell Transplantation, 24(11), 2367–2377.

    Article  PubMed  Google Scholar 

  139. Choi, E. W., et al. (2015). Transplantation of adipose tissue-derived mesenchymal stem cells prevents the development of lupus dermatitis. Stem Cells and Development, 24(17), 2041–2051.

    Article  CAS  PubMed  Google Scholar 

  140. Choi, E. W., et al. (2016). Mesenchymal stem cell transplantation can restore lupus disease-associated miRNA expression and Th1/Th2 ratios in a murine model of SLE. Scientific Reports, 6(1), 1–14.

    Article  CAS  Google Scholar 

  141. Zhang, Z., et al. (2019). Mesenchymal stem cells prevent podocyte injury in lupus-prone B6. MRL-Faslpr mice via polarizing macrophage into an anti-inflammatory phenotype. Nephrology, Dialysis, Transplantation, 34(4), 597–605.

    Article  CAS  PubMed  Google Scholar 

  142. Chang, J.-W., et al. (2011). Therapeutic effects of umbilical cord blood-derived mesenchymal stem cell transplantation in experimental lupus nephritis. Cell Transplantation, 20(2), 245–258.

    Article  PubMed  Google Scholar 

  143. Gu, Z., et al. (2010). Transplantation of umbilical cord mesenchymal stem cells alleviates lupus nephritis in MRL/lpr mice. Lupus, 19(13), 1502–1514.

    Article  CAS  PubMed  Google Scholar 

  144. Wang, D., et al. (2018). A long-term follow-up study of allogeneic mesenchymal stem/stromal cell transplantation in patients with drug-resistant systemic lupus erythematosus. Stem Cell Reports, 10(3), 933–941.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Gu, F., et al. (2014). Allogeneic mesenchymal stem cell transplantation for lupus nephritis patients refractory to conventional therapy. Clinical Rheumatology, 33(11), 1611–1619.

    Article  PubMed  Google Scholar 

  146. Shi, D., et al. (2012). Allogeneic transplantation of umbilical cord-derived mesenchymal stem cells for diffuse alveolar hemorrhage in systemic lupus erythematosus. Clinical Rheumatology, 31(5), 841–846.

    Article  PubMed  Google Scholar 

  147. Liang, J., et al. (2010). Allogenic mesenchymal stem cells transplantation in refractory systemic lupus erythematosus: A pilot clinical study. Annals of the Rheumatic Diseases, 69(8), 1423–1429.

    Article  PubMed  Google Scholar 

  148. Sun, L., et al. (2009). Mesenchymal stem cell transplantation reverses multiorgan dysfunction in systemic lupus erythematosus mice and humans. Stem Cells, 27(6), 1421–1432.

    Article  CAS  PubMed  Google Scholar 

  149. Yuan, X., et al. (2019). Mesenchymal stem cell therapy induces FLT3L and CD1c+ dendritic cells in systemic lupus erythematosus patients. Nature Communications, 10(1), 1–12.

    Article  Google Scholar 

  150. Sun, L., et al. (2010). Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus. Arthritis and Rheumatism, 62(8), 2467–2475.

    Article  CAS  PubMed  Google Scholar 

  151. Dema, B., et al. (2017). Basophils contribute to pristane-induced lupus-like nephritis model. Scientific Reports, 7(1), 7969.

    Article  PubMed  PubMed Central  Google Scholar 

  152. Wang, Q., et al. (2015). Combined transplantation of autologous hematopoietic stem cells and allogenic mesenchymal stem cells increases T regulatory cells in systemic lupus erythematosus with refractory lupus nephritis and leukopenia. Lupus, 24(11), 1221–1226.

    Article  CAS  PubMed  Google Scholar 

  153. Rezaieyazdi, Z., et al. (2014). Efficacy of long-term maintenance therapy with mycophenolate mofetil in lupus nephritis. Springerplus, 3, 638.

    Article  PubMed  PubMed Central  Google Scholar 

  154. Dang, J., et al. (2020). Human gingiva-derived mesenchymal stem cells are therapeutic in lupus nephritis through targeting of CD39−CD73 signaling pathway. Journal of Autoimmunity, 113, 102491.

    Article  CAS  PubMed  Google Scholar 

  155. Wang, D., et al. (2014). Umbilical cord mesenchymal stem cell transplantation in active and refractory systemic lupus erythematosus: A multicenter clinical study. Arthritis Research & Therapy, 16(2), R79.

    Article  Google Scholar 

  156. Schena, F., et al. (2010). Interferon-γ-dependent inhibition of B cell activation by bone marrow-derived mesenchymal stem cells in a murine model of systemic lupus erythematosus. Arthritis and Rheumatism, 62(9), 2776–2786.

    Article  CAS  PubMed  Google Scholar 

  157. Chen, X., Armstrong, M. A., & Li, G. (2006). Mesenchymal stem cells in immunoregulation. Immunology and Cell Biology, 84(5), 413–421.

    Article  CAS  PubMed  Google Scholar 

  158. Fathollahi, A., Gabalou, N. B., & Aslani, S. (2018). Mesenchymal stem cell transplantation in systemic lupus erythematous, a mesenchymal stem cell disorder. Lupus, 27(7), 1053–1064.

    Article  CAS  PubMed  Google Scholar 

  159. Sanz-Nogués, C., & O'Brien, T. (2021). Current good manufacturing practice considerations for mesenchymal stromal cells as therapeutic agents. Biomaterials and Biosystems, 2, 100018.

    Article  Google Scholar 

  160. Phinney, D. G., & Galipeau, J. (2019). Manufacturing mesenchymal stromal cells for clinical applications: A survey of good manufacturing practices at US academic centers. Cytotherapy, 21(7), 782–792.

    Article  PubMed  Google Scholar 

  161. Mizukami, A., et al. (2018). Technologies for large-scale umbilical cord-derived MSC expansion: Experimental performance and cost of goods analysis. Biochemical Engineering Journal, 135, 36–48.

    Article  Google Scholar 

  162. Kelly, K. (2015). Limitless starting materials for large-scale manufacture of MSCs–what does the future hold? Pharmaceutical Bioprocessing, 3(4), 281–283.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Immunology Research Center, Mashhad University of Medical Sciences, Pardi’s Campus, Azadi Square, Kalantari Blvd, Mashhad, Iran

    Mahmoud Mahmoudi & Akram Hoseinzadeh

  2. Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Pardi’s Campus, Azadi Square, Kalantari Blvd, Mashhad, Iran

    Mahmoud Mahmoudi & Akram Hoseinzadeh

  3. Department of Rheumatology, Ghaem Hospital, Mashhad University of Medical Science, Mashhad, Iran

    Zahra Rezaieyazdi

  4. Rheumatic Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Zahra Rezaieyazdi

  5. Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Jalil Tavakol Afshari

  6. Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Ali Mahmoudi

  7. Department of Physiology and Pharmacology, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran

    Sahar Heydari

Authors
  1. Mahmoud Mahmoudi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akram Hoseinzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zahra Rezaieyazdi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jalil Tavakol Afshari
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ali Mahmoudi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sahar Heydari
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HA has drafted the work. [First Author].

MM, RZ, TAJ thoroughly reviewed it.

MA and HS have drawn the figures.

All authors read and approved the final manuscript.

Corresponding author

Correspondence to Mahmoud Mahmoudi.

Ethics declarations

Ethics Approval and Consent to Participate

“Not applicable”.

Consent for Publication

“Not applicable”.

Competing Interests

All authors contributed equally.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article belongs to the Topical Collection: Special Issue on Tissue-resident stem/progenitor cells endowed with broader germ layer specification potential in normal and cancerous tissues

Guest Editor: Deepa Bhartiya

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mahmoudi, M., Hoseinzadeh, A., Rezaieyazdi, Z. et al. Cross Talk between Mesenchymal Stem/Stromal Cells and Innate Immunocytes Concerning Lupus Disease. Stem Cell Rev and Rep 18, 2781–2796 (2022). https://doi.org/10.1007/s12015-022-10397-x

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12015-022-10397-x

Keywords

Search

Navigation