Generic placeholder image

Current Drug Targets

Editor-in-Chief

ISSN (Print): 1389-4501
ISSN (Online): 1873-5592

Review Article (Mini-Review)

The Role of Immune and Epithelial Stem Cells in Inflammatory Bowel Disease Therapy

Author(s): Agata Binienda, Sylwia Ziolkowska, Ingvild H. Hauge and Maciej Salaga*

Volume 21 , Issue 14 , 2020

Page: [1405 - 1416] Pages: 12

DOI: 10.2174/1389450121666200504074922

Price: $65

Abstract

Background: Inflammatory Bowel Disease (IBD) is categorized as Crohn’s disease (CD) and Ulcerative colitis (UC) and is characterized by chronic inflammation in the gastrointestinal (GI) tract. Relapsing symptoms, including abdominal pain, increased stool frequency, loss of appetite as well as anemia contribute to significant deterioration of quality of life. IBD treatment encompasses chemotherapy (e.g. corticosteroids, thiopurines) and biological agents (e.g. antibodies targeting tumour necrosis factor α, interleukin 12/23) and surgery. However, efficacy of these therapies is not satisfactory. Thus, scientists are looking for new options in IBD treatment that could induce and maintain remission.

Objective: To summarize previous knowledge about role of different intestinal cells in IBD pathophysiology and application of stem cells in the IBD treatment.

Results: Recent studies have emphasized an important role of innate lymphoid cells (ILCs) as well as intestinal epithelial cells (IECs) in the IBD pathophysiology suggesting that these types of cells can be new targets for IBD treatment. Moreover, last studies show that stem cells transplantation reduces inflammation in patients suffering from IBD, which are resistant to conventional therapies.

Conclusion: Both hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are able to restore damaged tissue and regulate the immune system. Autologous HSCs transplantation eliminates autoreactive cells and replace them with new T-cells resulting a long-time remission. Whereas MSCs transplantation is effective therapy in one of the major complications of IBD, perianal fistulas.

Keywords: Stem cells, inflammatory bowel disease, perianal fistula, epithelial cells, innate lymphoid cells, enteropathies.

Graphical Abstract
[1]
Snowden JA, Panés J, Alexander T, et al. European Crohn’s and Colitis Organisation (ECCO); European Society for Blood and Marrow Transplantation (EBMT); Autoimmune Diseases Working Party (ADWP); Joint Accreditation Committee of the International Society for Cellular Therapy (ISCT) and EBMT (JACIE). Autologous haematopoietic stem cell transplantation (AHSCT) in severe Crohn’s disease: A review on behalf of ECCO and EBMT. J Crohn’s Colitis 2018; 12(4): 476-88.
[http://dx.doi.org/10.1093/ecco-jcc/jjx184 ] [PMID: 29325112]
[2]
Burisch J, Jess T, Martinato M, Lakatos PL. ECCO -EpiCom. The burden of inflammatory bowel disease in Europe. J Crohn’s Colitis 2013; 7(4): 322-37.
[http://dx.doi.org/10.1016/j.crohns.2013.01.010 ] [PMID: 23395397]
[3]
Snowden JA, Saccardi R, Allez M, et al. EBMT autoimmune disease working party (ADWP); paediatric diseases working party (PDWP). Haematopoietic SCT in severe autoimmune diseases: updated guidelines of the european group for blood and marrow transplantation. Bone Marrow Transplant 2012; 47(6): 770-90.
[http://dx.doi.org/10.1038/bmt.2011.185 ] [PMID: 22002489]
[4]
Salem GA, Selby GB. Stem cell transplant in inflammatory bowel disease: a promising modality of treatment for a complicated disease course. Stem Cell Investig 2017; 4: 95.
[http://dx.doi.org/10.21037/sci.2017.11.04 ] [PMID: 29270421]
[5]
Dave M, Papadakis KA, Faubion WA Jr. Immunology of inflammatory bowel disease and molecular targets for biologics. Gastroenterol Clin North Am 2014; 43(3): 405-24.
[http://dx.doi.org/10.1016/j.gtc.2014.05.003 ] [PMID: 25110250]
[6]
Artis D, Spits H. The biology of innate lymphoid cells. Nature 2015; 517(7534): 293-301.
[http://dx.doi.org/10.1038/nature14189 ] [PMID: 25592534]
[7]
Mjösberg J, Spits H. Human innate lymphoid cells. J Allergy Clin Immunol 2016; 138(5): 1265-76.
[http://dx.doi.org/10.1016/j.jaci.2016.09.009 ] [PMID: 27677386]
[8]
Ebbo M, Crinier A, Vély F, Vivier E. Innate lymphoid cells: major players in inflammatory diseases. Nat Rev Immunol 2017; 17(11): 665-78.
[http://dx.doi.org/10.1038/nri.2017.86 ] [PMID: 28804130]
[9]
Moschen AR, Tilg H, Raine T. IL-12, IL-23 and IL-17 in IBD: immunobiology and therapeutic targeting. Nat Rev Gastroenterol Hepatol 2019; 16(3): 185-96.
[http://dx.doi.org/10.1038/s41575-018-0084-8 ] [PMID: 30478416]
[10]
Eberl G, Di Santo JP, Vivier E. The brave new world of innate lymphoid cells. Nat Immunol 2015; 16(1): 1-5.
[http://dx.doi.org/10.1038/ni.3059 ] [PMID: 25521670]
[11]
Bernink JH, Peters CP, Munneke M, et al. Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues. Nat Immunol 2013; 14(3): 221-9.
[http://dx.doi.org/10.1038/ni.2534 ] [PMID: 23334791]
[12]
Zeng B, Shi S, Ashworth G, Dong C, Liu J, Xing F. ILC3 function as a double-edged sword in inflammatory bowel diseases. Cell Death Dis 2019; 10(4): 315.
[http://dx.doi.org/10.1038/s41419-019-1540-2 ] [PMID: 30962426]
[13]
Forkel M, Mjösberg J. Dysregulation of group 3 innate lymphoid cells in the pathogenesis of inflammatory bowel disease. Curr Allergy Asthma Rep 2016; 16(10): 73.
[http://dx.doi.org/10.1007/s11882-016-0652-3 ] [PMID: 27645534]
[14]
Hanash AM, Dudakov JA, Hua G, et al. Interleukin-22 protects intestinal stem cells from immune-mediated tissue damage and regulates sensitivity to graft versus host disease. Immunity 2012; 37(2): 339-50.
[http://dx.doi.org/10.1016/j.immuni.2012.05.028 ] [PMID: 22921121]
[15]
Pearson C, Thornton EE, McKenzie B, et al. ILC3 GM-CSF production and mobilisation orchestrate acute intestinal inflammation. Elife 2016; 5(JANUARY2016): 1-21.
[http://dx.doi.org/10.7554/eLife.10066]
[16]
Geremia A, Arancibia-Cárcamo CV, Fleming MPP, et al. IL-23-responsive innate lymphoid cells are increased in inflammatory bowel disease. J Exp Med 2011; 208(6): 1127-33.
[http://dx.doi.org/10.1084/jem.20101712 ] [PMID: 21576383]
[17]
Takayama T, Kamada N, Chinen H, et al. Imbalance of NKp44+NKp46- and NKp44 -NKp46+ natural killer cells in the intestinal mucosa of patients with Crohn’s disease. Gastroenterology 2010; 139(3): 882-92.
[http://dx.doi.org/10.1053/j.gastro.2010.05.040 ] [PMID: 20638936]
[18]
Glatzer T, Killig M, Meisig J, et al. RORγt+ innate lymphoid cells acquire a proinflammatory program upon engagement of the activating receptor NKp44. Immunity 2013; 38(6): 1223-35.
[http://dx.doi.org/10.1016/j.immuni.2013.05.013 ] [PMID: 23791642]
[19]
Bernink JH, Krabbendam L, Germar K, et al. Interleukin-12 and -23 control plasticity of cd127(+) group 1 and group 3 innate lymphoid cells in the intestinal lamina propria. Immunity 2015; 43(1): 146-60.
[http://dx.doi.org/10.1016/j.immuni.2015.06.019 ] [PMID: 26187413]
[20]
Okamoto R, Watanabe M. Role of epithelial cells in the pathogenesis and treatment of inflammatory bowel disease. J Gastroenterol 2016; 51(1): 11-21.
[http://dx.doi.org/10.1007/s00535-015-1098-4 ] [PMID: 26138071]
[21]
Allaire JM, Crowley SM, Law HT, Chang SY, Ko HJ, Vallance BA. The intestinal epithelium: central coordinator of mucosal immunity. Trends Immunol 2018; 39(9): 677-96.
[http://dx.doi.org/10.1016/j.it.2018.04.002 ] [PMID: 29716793]
[22]
Christ AD, Blumberg RS. The intestinal epithelial cell: immunological aspects 1997; 18(4): 449-61.
[http://dx.doi.org/10.1007/BF00824052 ]
[23]
Umar S. Intestinal stem cells. Curr Gastroenterol Rep 2010; 12(5): 340-8.
[http://dx.doi.org/10.1007/s11894-010-0130-3 ] [PMID: 20683682]
[24]
Snoeck V, Goddeeris B, Cox E. The role of enterocytes in the intestinal barrier function and antigen uptake. Microbes Infect 2005; 7(7-8): 997-1004.
[http://dx.doi.org/10.1016/j.micinf.2005.04.003 ] [PMID: 15925533]
[25]
Gribble FM, Reimann F. Function and mechanisms of enteroendocrine cells and gut hormones in metabolism. Nat Rev Endocrinol 2019; 15(4): 226-37.
[http://dx.doi.org/10.1038/s41574-019-0168-8 ] [PMID: 30760847]
[26]
Gunawardene AR, Corfe BM, Staton CA. Classification and functions of enteroendocrine cells of the lower gastrointestinal tract. Int J Exp Pathol 2011; 92(4): 219-31.
[http://dx.doi.org/10.1111/j.1365-2613.2011.00767.x ] [PMID: 21518048]
[27]
McDole JR, Wheeler LW, McDonald KG, et al. Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine. Nature 2012; 483(7389): 345-9.
[http://dx.doi.org/10.1038/nature10863 ] [PMID: 22422267]
[28]
Birchenough GMH, Johansson MEV, Gustafsson JK, Bergström JH, Hansson GC. New developments in goblet cell mucus secretion and function. Mucosal Immunol 2015; 8(4): 712-9.
[http://dx.doi.org/10.1038/mi.2015.32 ] [PMID: 25872481]
[29]
Vaishnava S, Behrendt CL, Ismail AS, Eckmann L, Hooper LV. Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface. Proc Natl Acad Sci USA 2008; 105(52): 20858-63.
[http://dx.doi.org/10.1073/pnas.0808723105 ] [PMID: 19075245]
[30]
Keshav S. Paneth cells: leukocyte-like mediators of innate immunity in the intestine. J Leukoc Biol 2006; 80(3): 500-8.
[http://dx.doi.org/10.1189/jlb.1005556 ] [PMID: 16793911]
[31]
Cader MZ, Kaser A. Recent advances in inflammatory bowel disease: mucosal immune cells in intestinal inflammation. Gut 2013; 62(11): 1653-64.
[http://dx.doi.org/10.1136/gutjnl-2012-303955 ] [PMID: 24104886]
[32]
Roulis M, Armaka M, Manoloukos M, Apostolaki M, Kollias G. Intestinal epithelial cells as producers but not targets of chronic TNF suffice to cause murine Crohn-like pathology. Proc Natl Acad Sci USA 2011; 108(13): 5396-401.
[http://dx.doi.org/10.1073/pnas.1007811108 ] [PMID: 21402942]
[33]
Vetrano S, Ploplis VA, Sala E, et al. Unexpected role of anticoagulant protein C in controlling epithelial barrier integrity and intestinal inflammation. Proc Natl Acad Sci USA 2011; 108(49): 19830-5.
[http://dx.doi.org/10.1073/pnas.1107140108 ] [PMID: 22109555]
[34]
Pickert G, Neufert C, Leppkes M, et al. STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing. J Exp Med 2009; 206(7): 1465-72.
[http://dx.doi.org/10.1084/jem.20082683 ] [PMID: 19564350]
[35]
Olszak T, Neves JF, Dowds CM, et al. Protective mucosal immunity mediated by epithelial CD1d and IL-10. Nature 2014; 509(7501): 497-502.
[http://dx.doi.org/10.1038/nature13150 ] [PMID: 24717441]
[36]
Aden K, Rehman A, Falk-Paulsen M, et al. Epithelial il-23r signaling licenses protective il-22 responses in intestinal inflammation. Cell Rep 2016; 16(8): 2208-18.
[http://dx.doi.org/10.1016/j.celrep.2016.07.054 ] [PMID: 27524624]
[37]
Abreu MT. Toll-like receptor signalling in the intestinal epithelium: how bacterial recognition shapes intestinal function. Nat Rev Immunol 2010; 10(2): 131-44.
[http://dx.doi.org/10.1038/nri2707 ] [PMID: 20098461]
[38]
Turgeon N, Blais M, Gagné JM, et al. HDAC1 and HDAC2 restrain the intestinal inflammatory response by regulating intestinal epithelial cell differentiation. PLoS One 2013; 8(9)e73785
[http://dx.doi.org/10.1371/journal.pone.0073785 ] [PMID: 24040068]
[39]
Balzola F, Bernstein C, Ho GT, Lees C. Immunoregulatory actions of epithelial cell PPAR gamma at the colonic mucosa of mice with experimental inflammatory bowel disease. Inflamm Bowel Dis Monit 2010; 11(1): 31. [Commentary
[40]
Kaser A, Zeissig S, Blumberg RS. Inflammatory bowel disease. Annu Rev Immunol 2010; 28(5): 573-621.
[http://dx.doi.org/10.1146/annurev-immunol-030409-101225 ] [PMID: 20192811]
[41]
Van der Sluis M, De Koning BAE, De Bruijn ACJM, et al. Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology 2006; 131(1): 117-29.
[http://dx.doi.org/10.1053/j.gastro.2006.04.020 ] [PMID: 16831596]
[42]
Schnoor M. E-cadherin is important for the maintenance of intestinal epithelial homeostasis under basal and inflammatory conditions. Dig Dis Sci 2015; 60(4): 816-8.
[http://dx.doi.org/10.1007/s10620-015-3622-z ] [PMID: 25772779]
[43]
Zbar AP, Simopoulos C, Karayiannakis AJ. Cadherins: an integral role in inflammatory bowel disease and mucosal restitution. J Gastroenterol 2004; 39(5): 413-21.
[http://dx.doi.org/10.1007/s00535-004-1335-8 ] [PMID: 15175938]
[44]
Mizoguchi A, Takeuchi T, Himuro H, Okada T, Mizoguchi E. Genetically engineered mouse models for studying inflammatory bowel disease. J Pathol 2016; 238(2): 205-19.
[http://dx.doi.org/10.1002/path.4640 ] [PMID: 26387641]
[45]
Mehta S, Nijhuis A, Kumagai T, Lindsay J, Silver A. Defects in the adherens junction complex (E-cadherin/β-catenin) in inflammatory bowel disease. Cell Tissue Res 2015; 360(3): 749-60.
[http://dx.doi.org/10.1007/s00441-014-1994-6 ] [PMID: 25238996]
[46]
Smalley-Freed WG, Efimov A, Burnett PE, et al. p120-catenin is essential for maintenance of barrier function and intestinal homeostasis in mice. J Clin Invest 2010; 120(6): 1824-35.
[http://dx.doi.org/10.1172/JCI41414 ] [PMID: 20484816]
[47]
Günther C, Martini E, Wittkopf N, et al. Caspase-8 regulates TNF-α-induced epithelial necroptosis and terminal ileitis. Nature 2011; 477(7364): 335-9.
[http://dx.doi.org/10.1038/nature10400 ] [PMID: 21921917]
[48]
Nenci A, Becker C, Wullaert A, et al. Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature 2007; 446(7135): 557-61.
[http://dx.doi.org/10.1038/nature05698 ] [PMID: 17361131]
[49]
Zitvogel L, Kepp O, Kroemer G. Decoding cell death signals in inflammation and immunity. Cell 2010; 140(6): 798-804.
[http://dx.doi.org/10.1016/j.cell.2010.02.015 ] [PMID: 20303871]
[50]
Peterson LW, Artis D. Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat Rev Immunol 2014; 14(3): 141-53.
[http://dx.doi.org/10.1038/nri3608 ] [PMID: 24566914]
[51]
Larabi A, Barnich N, Nguyen HTT. New insights into the interplay between autophagy, gut microbiota and inflammatory responses in IBD. Autophagy 2019; 0(0): 1-14.
[PMID: 31286804]
[52]
Kelly D, Kotliar M, Woo V, et al. Microbiota-sensitive epigenetic signature predicts inflammation in Crohn’s disease. JCI Insight 2018; 3(18): 1-14.
[http://dx.doi.org/10.1172/jci.insight.122104 ] [PMID: 30232290]
[53]
Cao SS. Epithelial ER stress in Crohn’s disease and ulcerative colitis. Inflamm Bowel Dis 2016; 22(4): 984-93.
[http://dx.doi.org/10.1097/MIB.0000000000000660 ] [PMID: 26950312]
[54]
Ma X, Dai Z, Sun K, et al. Intestinal epithelial cell endoplasmic reticulum stress and inflammatory bowel disease pathogenesis: An update review. Front Immunol 2017; 8: 1271.
[http://dx.doi.org/10.3389/fimmu.2017.01271 ] [PMID: 29118753]
[55]
Kaser A, Lee A-H, Franke A, et al. XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell 2008; 134(5): 743-56.
[http://dx.doi.org/10.1016/j.cell.2008.07.021 ] [PMID: 18775308]
[56]
Shanahan MT, Carroll IM, Gulati AS. Critical design aspects involved in the study of Paneth cells and the intestinal microbiota. Gut Microbes 2014; 5(2): 208-14.
[http://dx.doi.org/10.4161/gmic.27466 ] [PMID: 24637592]
[57]
Cadwell K, Liu J, Brown SL, Miyoshi H, Loh J, Lennerz J, et al. A unique role for autophagy and Atg16L1 in Paneth cells in murine and human intestine. Nature 2008; 456(7219): 259-63.
[http://dx.doi.org/10.1038/nature07416 ] [PMID: 18849966]
[58]
Wang SL, Shao BZ, Zhao SB, et al. Impact of paneth cell autophagy on inflammatory bowel disease. Front Immunol 2018; 9: 693.
[http://dx.doi.org/10.3389/fimmu.2018.00693 ] [PMID: 29675025]
[59]
Grimm MC, Pavli P. NOD2 mutations and Crohn’s disease: are Paneth cells and their antimicrobial peptides the link? Gut 2004; 53(11): 1558-60.
[http://dx.doi.org/10.1136/gut.2004.043307 ] [PMID: 15479670]
[60]
López-Posadas R, Becker C, Günther C, et al. Rho-A prenylation and signaling link epithelial homeostasis to intestinal inflammation. J Clin Invest 2016; 126(2): 611-26.
[http://dx.doi.org/10.1172/JCI80997 ] [PMID: 26752649]
[61]
Shimizu H, Suzuki K, Watanabe M, Okamoto R. Stem cell-based therapy for inflammatory bowel disease. Intest Res 2019; 17(3): 311-6.2019/07/25.
[http://dx.doi.org/10.5217/ir.2019.00043]
[62]
Irhimeh MR, Cooney J. Management of inflammatory bowel disease using stem cell therapy. Curr Stem Cell Res Ther 2016; 11(1): 72-7.
[http://dx.doi.org/10.2174/1574888X10666150728121738 ] [PMID: 26216128]
[63]
Hordyjewska A, Popiołek Ł, Horecka A. Characteristics of hematopoietic stem cells of umbilical cord blood. Cytotechnology 2015; 67(3): 387-96.
[http://dx.doi.org/10.1007/s10616-014-9796-y ] [PMID: 25373337]
[64]
Kondo M. Lymphoid and myeloid lineage commitment in multipotent hematopoietic progenitors. Immunol Rev 2010; 238(1): 37-46.
[http://dx.doi.org/10.1111/j.1600-065X.2010.00963.x ] [PMID: 20969583]
[65]
Mishra T, Sarswat A, Mishra KS, Srivastava A. Inflammatory bowel diseases: current therapeutic approaches and potential of using stem cells. J Stem Cell Res Ther 2017; 2(2): 45-57.
[66]
Burt RK, Craig RM, Milanetti F, et al. Autologous nonmyeloablative hematopoietic stem cell transplantation in patients with severe anti-TNF refractory Crohn disease: long-term follow-up. Blood 2010; 116(26): 6123-32.
[http://dx.doi.org/10.1182/blood-2010-06-292391 ] [PMID: 20837778]
[67]
Hawkey CJ, Allez M, Clark MM, et al. Autologous hematopoetic stem cell transplantation for refractory Crohn disease a randomized clinical trial. JAMA -. JAMA 2015; 314(23): 2524-34.
[http://dx.doi.org/10.1001/jama.2015.16700 ] [PMID: 26670970]
[68]
Burt RK, Kaiser RL Jr, Ruiz MA. Stem-cell transplantation for Crohn’s disease: same authors, different conclusions? Lancet Gastroenterol Hepatol 2017; 2(6): 386-7.
[http://dx.doi.org/10.1016/S2468-1253(17)30076-6 ] [PMID: 28497747]
[69]
Lindsay JO, Allez M, Clark M, et al. ASTIC trial group; european society for blood and marrow transplantation autoimmune disease working party; European crohn’s and colitis organisation. autologous stem-cell transplantation in treatment-refractory crohn’s disease: an analysis of pooled data from the astic trial. Lancet Gastroenterol Hepatol 2017; 2(6): 399-406.
[http://dx.doi.org/10.1016/S2468-1253(17)30056-0 ] [PMID: 28497755]
[70]
López-García A, Rovira M, Jauregui-Amezaga A, et al. Autologous haematopoietic stem cell transplantation for refractory crohn’s disease: Efficacy in a single-centre cohort. J Crohn’s Colitis 2017; 11(10): 1161-8.
[http://dx.doi.org/10.1093/ecco-jcc/jjx054 ] [PMID: 28419282]
[71]
Ribeiro AF, Oba J, Silva CC, et al. Autologous hematopoietic stem cell transplantation in refractory crohn’s disease. experience of tertiary medical center in Brazil. Biol Blood Marrow Transplant 2019; 25(3): 318-9.
[http://dx.doi.org/10.1016/j.bbmt.2018.12.514]
[72]
Brierley CK, Castilla-Llorente C, Labopin M, et al. European Society for Blood and Marrow Transplantation [EBMT] Autoimmune Diseases Working Party [ADWP Autologous haematopoietic stem cell transplantation for crohn’s disease: a retrospective survey of long-term outcomes from the european society for blood and marrow transplantation. J Crohn’s Colitis 2018; 12(9): 1097-103.
[http://dx.doi.org/10.1093/ecco-jcc/jjy069 ] [PMID: 29788233]
[73]
Camus M, Esses S, Pariente B, et al. Oligoclonal expansions of mucosal T cells in Crohn’s disease predominate in NKG2D-expressing CD4 T cells. Mucosal Immunol 2014; 7(2): 325-34.
[http://dx.doi.org/10.1038/mi.2013.51 ] [PMID: 23945543]
[74]
Le Bourhis L, Corraliza AM, Auzolle C, et al. Resetting of the mucosal t cell repertoire after hematopoietic stem cell transplantation in refractory crohn’s disease. Gastroenterology 2017; 152(5): 613-4.
[http://dx.doi.org/10.1016/S0016-5085(17)32180-7]
[75]
Allez M. Autologous stem cell transplantation as a reset option? UEG Week 2018 Oral Presentations (IP392) United Eur Gastroenterol J 2018; 6(8_suppl): A1-A134.
[76]
Arai F, Ohneda O, Miyamoto T, Zhang XQ, Suda T. Mesenchymal stem cells in perichondrium express activated leukocyte cell adhesion molecule and participate in bone marrow formation. J Exp Med 2002; 195(12): 1549-63.
[http://dx.doi.org/10.1084/jem.20011700 ] [PMID: 12070283]
[77]
Young HE, Steele TA, Bray RA, et al. Human reserve pluripotent mesenchymal stem cells are present in the connective tissues of skeletal muscle and dermis derived from fetal, adult, and geriatric donors. Anat Rec 2001; 264(1): 51-62.
[http://dx.doi.org/10.1002/ar.1128 ] [PMID: 11505371]
[78]
in ’t Anker PS, Noort WA, Scherjon SA, et al. Mesenchymal stem cells in human second-trimester bone marrow, liver, lung, and spleen exhibit a similar immunophenotype but a heterogeneous multilineage differentiation potential. Haematologica 2003; 88(8): 845-52.
[PMID: 12935972]
[79]
In ’t Anker PS, Scherjon SA, Kleijburg-van der Keur C, et al. Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta. Stem Cells 2004; 22(7): 1338-45.
[http://dx.doi.org/10.1634/stemcells.2004-0058 ] [PMID: 15579651]
[80]
Bieback K, Kern S, Klüter H, Eichler H. Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells 2004; 22(4): 625-34.
[http://dx.doi.org/10.1634/stemcells.22-4-625 ] [PMID: 15277708]
[81]
In ’t Anker PS, Scherjon SA, Kleijburg-van der Keur C, et al. Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. Blood 2003; 102(4): 1548-9.
[http://dx.doi.org/10.1182/blood-2003-04-1291 ] [PMID: 12900350]
[82]
Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005; 105(4): 1815-22.
[http://dx.doi.org/10.1182/blood-2004-04-1559 ] [PMID: 15494428]
[83]
Mayne CG, Williams CB. Induced and natural regulatory T cells in the development of inflammatory bowel disease. Inflamm Bowel Dis 2013; 19(8): 1772-88.
[http://dx.doi.org/10.1097/MIB.0b013e318281f5a3 ] [PMID: 23656897]
[84]
Melief SM, Schrama E, Brugman MH, et al. Multipotent stromal cells induce human regulatory T cells through a novel pathway involving skewing of monocytes toward anti-inflammatory macrophages. Stem Cells 2013; 31(9): 1980-91.
[http://dx.doi.org/10.1002/stem.1432 ] [PMID: 23712682]
[85]
Rutella S, Locatelli F. Intestinal dendritic cells in the pathogenesis of inflammatory bowel disease. World J Gastroenterol 2011; 17(33): 3761-75.
[http://dx.doi.org/10.3748/wjg.v17.i33.3761 ] [PMID: 21987618]
[86]
Joel MDM, Yuan J, Wang J, et al. MSC: immunoregulatory effects, roles on neutrophils and evolving clinical potentials. Am J Transl Res 2019; 11(6): 3890-904.
[PMID: 31312397]
[87]
Corcione A, Benvenuto F, Ferretti E, et al. Human mesenchymal stem cells modulate B-cell functions. Blood 2006; 107(1): 367-72.
[http://dx.doi.org/10.1182/blood-2005-07-2657 ] [PMID: 16141348]
[88]
García-Olmo D, García-Arranz M, Herreros D, Pascual I, Peiro C, Rodríguez-Montes JA. A phase I clinical trial of the treatment of Crohn’s fistula by adipose mesenchymal stem cell transplantation. Dis Colon Rectum 2005; 48(7): 1416-23.
[http://dx.doi.org/10.1007/s10350-005-0052-6 ] [PMID: 15933795]
[89]
Garcia-Olmo D, Herreros D, Pascual I, et al. Expanded adipose-derived stem cells for the treatment of complex perianal fistula: a phase II clinical trial. Dis Colon Rectum 2009; 52(1): 79-86.
[http://dx.doi.org/10.1007/DCR.0b013e3181973487 ] [PMID: 19273960]
[90]
Molendijk I, Bonsing BA, Roelofs H, et al. Allogeneic bone marrow-derived mesenchymal stromal cells promote healing of refractory perianal fistulas in patients with crohn’s disease. Gastroenterology 2015; 149(4): 918-27.e6.
[http://dx.doi.org/10.1053/j.gastro.2015.06.014 ] [PMID: 26116801]
[91]
Panés J, García-Olmo D, Van Assche G, et al. ADMIRE cd study group collaborators. 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(10051): 1281-90.
[http://dx.doi.org/10.1016/S0140-6736(16)31203-X ] [PMID: 27477896]
[92]
Panés J, García-Olmo D, Van Assche G, et al. ADMIRE CD Study Group Collaborators. Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn’s Disease. Gastroenterology 2018; 154(5): 1334-1342.e4.
[http://dx.doi.org/10.1053/j.gastro.2017.12.020 ] [PMID: 29277560]
[93]
de la Portilla F, Alba F, García-Olmo D, Herrerías JM, González FX, Galindo A. Expanded allogeneic adipose-derived stem cells (eASCs) for the treatment of complex perianal fistula in Crohn’s disease: results from a multicenter phase I/IIa clinical trial. Int J Colorectal Dis 2013; 28(3): 313-23.
[http://dx.doi.org/10.1007/s00384-012-1581-9 ] [PMID: 23053677]
[94]
Burns AJ, Thapar N. Neural stem cell therapies for enteric nervous system disorders. Nat Rev Gastroenterol Hepatol 2014; 11(5): 317-28.
[http://dx.doi.org/10.1038/nrgastro.2013.226 ] [PMID: 24322895]
[95]
Kruger GM, Mosher JT, Bixby S, Joseph N, Iwashita T, Morrison SJ. Neural crest stem cells persist in the adult gut but undergo changes in self-renewal, neuronal subtype potential, and factor responsiveness. Neuron 2002; 35(4): 657-69.
[http://dx.doi.org/10.1016/S0896-6273(02)00827-9 ] [PMID: 12194866]
[96]
Bondurand N, Natarajan D, Thapar N, Atkins C, Pachnis V. Neuron and glia generating progenitors of the mammalian enteric nervous system isolated from foetal and postnatal gut cultures. Development 2003; 130(25): 6387-400.
[http://dx.doi.org/10.1242/dev.00857 ] [PMID: 14623827]
[97]
Cooper JE, McCann CJ, Natarajan D, et al. In vivo transplantation of enteric neural crest cells into mouse gut; Engraftment, functional integration and long-term safety. PLoS One 2016; 11(1)e0147989
[http://dx.doi.org/10.1371/journal.pone.0147989 ] [PMID: 26824433]
[98]
McCann CJ, Cooper JE, Natarajan D, et al. Transplantation of enteric nervous system stem cells rescues nitric oxide synthase deficient mouse colon. Nat Commun 2017; 8: 15937.
[http://dx.doi.org/10.1038/ncomms15937 ] [PMID: 28671186]
[99]
Metzger M, Caldwell C, Barlow AJ, Burns AJ, Thapar N. Enteric nervous system stem cells derived from human gut mucosa for the treatment of aganglionic gut disorders. Gastroenterology 2009; 136(7): 2214-25. e1 ,3.
[http://dx.doi.org/10.1053/j.gastro.2009.02.048] [PMID: 19505425]
[100]
Cheng LS, Hotta R, Graham HK, Belkind-Gerson J, Nagy N, Goldstein AM. Postnatal human enteric neuronal progenitors can migrate, differentiate, and proliferate in embryonic and postnatal aganglionic gut environments. Pediatr Res 2017; 81(5): 838-46.
[http://dx.doi.org/10.1038/pr.2017.4 ] [PMID: 28060794]
[101]
Fattahi F, Steinbeck JA, Kriks S, et al. Deriving human ENS lineages for cell therapy and drug discovery in Hirschsprung disease. Nature 2016; 531(7592): 105-9.
[http://dx.doi.org/10.1038/nature16951 ] [PMID: 26863197]
[102]
Yoshida H, Okamoto K, Iwamoto T, et al. Pepstatin A, an aspartic proteinase inhibitor, suppresses RANKL-induced osteoclast differentiation. J Biochem 2006; 139(3): 583-90.
[http://dx.doi.org/10.1093/jb/mvj066 ] [PMID: 16567424]
[103]
Workman MJ, Mahe MM, Trisno S, et al. Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system. Nat Med 2017; 23(1): 49-59.
[http://dx.doi.org/10.1038/nm.4233 ] [PMID: 27869805]
[104]
Burns AJ, Goldstein AM, Newgreen DF, et al. White paper on guidelines concerning enteric nervous system stem cell therapy for enteric neuropathies. Dev Biol 2016; 417(2): 229-51.
[http://dx.doi.org/10.1016/j.ydbio.2016.04.001 ] [PMID: 27059883]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy