Skip to main content
SpringerLink
Log in

An Update on the Therapeutic Potential of Stem Cells

  • Protocol
  • First Online:
Somatic Stem Cells

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1842))

Abstract

The seeming setbacks noted for stem cells underscore the need for experimental studies for safe and efficacious application to patients. Both clinical and experimental researchers have gained valuable knowledge on the characteristics of stem cells, and their behavior in different microenvironment. This introductory chapter focuses on adult mesenchymal stem cells (MSCs) based on the predominance in the clinic. MSCs can be influenced by inflammatory mediators to exert immune suppressive properties, commonly referred to as “licensing.” Interestingly, while there are questions if other stem cells can be delivered across allogeneic barrier, there is no question on the ability of MSCs to provide this benefit. This property has been a great advantage since MSCs could be available for immediate application as “off-the-shelf” stem cells for several disorders, tissue repair and gene/drug delivery. Despite the benefit of MSCs, it is imperative that research continues with the various types of stem cells. The method needed to isolate these cells is outlined in this book. In parallel, safety studies are needed; particularly links to oncogenic event. In summary, this introductory chapter discusses several potential areas that need to be addressed for safe and efficient delivery of stem cells, and argue for the incorporation of microenvironmental factors in the studies. The method described in this chapter could be extrapolated to the field of chimeric antigen receptor T-cells (CAR-T). This will require application to stem cell hierarchy of memory T-cells.

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

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Sell S (2010) On the stem cell origin of cancer. Am J Pathol 176:2584–2594

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Sell S (2004) Stem cell origin of cancer and differentiation therapy. Crit Rev Oncol Hematol 51:1–28

    Article  PubMed  Google Scholar 

  3. Roberto A, Castagna L, Zanon V et al (2015) Role of naive-derived T memory stem cells in T-cell reconstitution following allogeneic transplantation. Blood 125:2855–2864

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Frank NY, Schatton T, Frank MH (2010) The therapeutic promise of the cancer stem cell concept. J Clin Invest 120(1):41–50

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Baumann M, Krause M, Hill R (2008) Exploring the role of cancer stem cells in radioresistance. Nat Rev Cancer 8:545–554

    Article  PubMed  CAS  Google Scholar 

  6. McCulloch EA, Till JE (2005) Perspectives on the properties of stem cells. Nat Med 11:1026–1028

    Article  PubMed  CAS  Google Scholar 

  7. Drukker M, Katchman H, Katz G et al (2006) Human embryonic stem cells and their differentiated derivatives are less susceptible to immune rejection than adult cells. Stem Cells 24:221–229

    Article  PubMed  Google Scholar 

  8. Li L, Baroja ML, Majumdar A et al (2004) Human embryonic stem cells possess immune-privileged properties. Stem Cells 22:448–456

    Article  PubMed  CAS  Google Scholar 

  9. Swijnenburg RJ, Schrepfer S, Govaert JA et al (2008) Immunosuppressive therapy mitigates immunological rejection of human embryonic stem cell xenografts. Proc Natl Acad Sci 105:12991–12996

    Article  PubMed  PubMed Central  Google Scholar 

  10. Blum B, Benvenisty N (2008) The tumorigenicity of human embryonic stem cells. In: George FV (ed) Advances in cancer research, vol 100. Academic Press, Cambridge, pp 133–158

    Google Scholar 

  11. Ilic D, Ogilvie C (2017) Concise review: human embryonic stem cells-what have we done? What are we doing? Where are we going? Stem Cells 35:17–25

    Article  PubMed  CAS  Google Scholar 

  12. Parolini O, Alviano F, Bagnara GP et al (2008) Concise review: isolation and characterization of cells from human term placenta: outcome of the first international workshop on placenta derived stem cells. Stem Cells 26:300–311

    Article  PubMed  Google Scholar 

  13. Dan YY, Riehle KJ, Lazaro C et al (2006) Isolation of multipotent progenitor cells from human fetal liver capable of differentiating into liver and mesenchymal lineages. Proc Natl Acad Sci 103:9912–9917

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. De Coppi P, Bartsch G, Siddiqui MM et al (2007) Isolation of amniotic stem cell lines with potential for therapy. Nat Biotechnol 25:100–106

    Article  PubMed  CAS  Google Scholar 

  15. Perin L, Sedrakyan S, Giuliani S et al (2010) Protective effect of human amniotic fluid stem cells in an immunodeficient mouse model of acute tubular necrosis. PLoS One 5(2):e9357

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Siegel N, Rosner M, Unbekandt M et al (2010) Contribution of human amniotic fluid stem cells to renal tissue formation depends on mTOR. Hum Mol Genet 19:3320–3331

    Article  PubMed  CAS  Google Scholar 

  17. Fuchs E (2008) Skin stem cells: rising to the surface. J Cell Biol 180:273–284

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Takebe N, Ivy SP (2010) Controversies in cancer stem cells: targeting embryonic signaling pathways. Clin Cancer Res 16:3106–3112

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Tomasetti C, Vogelstein B (2015) Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science 347:78–81

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Clement V, Dutoit V, Marino D et al (2009) Limits of CD133 as a marker of glioma self-renewing cells. Int J Cancer 125:244–248

    Article  PubMed  CAS  Google Scholar 

  21. DA Cruz PA, Lopes C (2017) Implications of different cancer stem cell phenotypes in breast cancer. Anticancer Res 37:2173–2183

    Article  Google Scholar 

  22. Lee OK, Kuo TK, Chen WM et al (2004) Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood 103:1669–1675

    Article  PubMed  CAS  Google Scholar 

  23. Greco SJ, Liu K, Rameshwar P (2007) Functional similarities among genes regulated by Oct4 in human Mesenchymal and embryonic stem cells. Stem Cells 25:3143–3154

    Article  PubMed  CAS  Google Scholar 

  24. Woodward WA, Chen MS, Behbod F et al (2005) On mammary stem cells. J Cell Sci 118:3585–3594

    Article  PubMed  CAS  Google Scholar 

  25. Sugiyama T, Nagasawa T (2012) Bone marrow niches for hematopoietic stem cells and immune cells. Inflamm Allergy Drug Targets 11:201–206

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. de Souza LE, Malta TM, Kashima Haddad S et al (2016) Mesenchymal stem cells and pericytes: to what extent are they related? Stem Cells Dev 25:1843–1852

    Article  PubMed  Google Scholar 

  27. Castillo M, Liu K, Bonilla LM et al (2007) The immune properties of mesenchymal stem cells. Intl J Biomed Sci 3:100–104

    Google Scholar 

  28. Sakaguchi Y, Sekiya I, Yagishita K et al (2004) Suspended cells from trabecular bone by collagenase digestion become virtually identical to mesenchymal stem cells obtained from marrow aspirates. Blood 104:2728–2735

    Article  PubMed  CAS  Google Scholar 

  29. Meliga E, Strem BM, Duckers HJ et al (2007) Adipose-derived cells. Cell Transplant 16:963–970

    Article  PubMed  Google Scholar 

  30. Baksh D, Yao R, Tuan RS (2007) Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow. Stem Cells 25:1384–1392

    Article  PubMed  CAS  Google Scholar 

  31. Troyer DL, Weiss ML (2008) Wharton’s jelly-derived cells are a primitive stromal cell population. Stem Cells 26:591–599

    Article  PubMed  Google Scholar 

  32. Caplan AI (1994) The mesengenic process. Clin Plast Surg 21:429–435

    PubMed  CAS  Google Scholar 

  33. Fernandez-Moure JS, Corradetti B, Chan P et al (2015) Enhanced osteogenic potential of mesenchymal stem cells from cortical bone: a comparative analysis. Stem Cell Res Ther 6:203

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Delorme B, Ringe J, Gallay N et al (2008) Specific plasma membrane protein phenotype of culture-amplified and native human bone marrow mesenchymal stem cells. Blood 111(5):2631–2635

    Article  PubMed  CAS  Google Scholar 

  35. Sacchetti B, Funari A, Michienzi S et al (2007) Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell 131:324–336

    Article  PubMed  CAS  Google Scholar 

  36. Deng J, Petersen BE, Steindler DA et al (2006) Mesenchymal stem cells spontaneously express neural proteins in culture and are neurogenic after transplantation. Stem Cells 24:1054–1064

    Article  PubMed  CAS  Google Scholar 

  37. Martinez C, Hofmann TJ, Marino R et al (2007) Human bone marrow mesenchymal stromal cells express the neural ganglioside GD2: a novel surface marker for the identification of MSCs. Blood 109:4245–4248

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Padovan CS, Jahn K, Birnbaum T et al (2003) Expression of neuronal markers in differentiated marrow stromal cells and CD133+ stem-like cells. Cell Transplant 12:839–848

    Article  PubMed  Google Scholar 

  39. Greco SJ, Zhou C, Ye JH et al (2007) An interdisciplinary approach and characterization of neuronal cells transdifferentiated from human mesenchymal stem cells. Stem Cells Dev 16:811–826

    Article  PubMed  CAS  Google Scholar 

  40. Trzaska KA, King CC, Li KY et al (2009) Brain-derived neurotrophic factor facilitates maturation of mesenchymal stem cell-derived dopamine progenitors to functional neurons. J Neurochem 110:1058–1069

    Article  PubMed  CAS  Google Scholar 

  41. Trzaska KA, Reddy BY, Munoz JL et al (2008) Loss of RE-1 silencing factor in mesenchymal stem cell-derived dopamine progenitors induces functional maturity. Mol Cell Neurosci 39:285–290

    Article  PubMed  CAS  Google Scholar 

  42. Potian JA, Aviv H, Ponzio NM et al (2003) Veto-like activity of mesenchymal stem cells: functional discrimination between cellular responses to alloantigens and recall antigens. J Immunol 171:3426–3434

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  44. Pittenger MF, Mackay AM, Beck SC et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  46. Caplan AI (2008) All MSCs are pericytes? Cell Stem Cell 3:229–230

    Article  PubMed  CAS  Google Scholar 

  47. Takashima Y, Era T, Nakao K et al (2007) Neuroepithelial cells supply an initial transient wave of MSC differentiation. Cell 129:1377–1388

    Article  PubMed  CAS  Google Scholar 

  48. Trzaska KA, Kuzhikandathil EV, Rameshwar P (2007) Specification of a dopaminergic phenotype from adult human mesenchymal stem cells. Stem Cells 25:2797–2808

    Article  PubMed  CAS  Google Scholar 

  49. Brohlin M, Mahay D, Novikov LN et al (2009) Characterisation of human mesenchymal stem cells following differentiation into Schwann cell-like cells. Neurosci Res 64:41–49

    Article  PubMed  Google Scholar 

  50. Cho KJ, Trzaska KA, Greco SJ et al (2005) Neurons derived from human mesenchymal stem cells show synaptic transmission and can be induced to produce the neurotransmitter substance P by interleukin-1{alpha}. Stem Cells 23:383–391

    Article  PubMed  CAS  Google Scholar 

  51. Sherman LS, Shaker M, Mariotti V et al (2017) Mesenchymal stromal/stem cells in drug therapy: new perspective. Cytotherapy 19:19–27

    Article  PubMed  Google Scholar 

  52. Ben JJ, Steven JM (2008) Immunosuppression by mesenchymal stromal cells: from culture to clinic. Exp Hematol 36:733–741

    Article  CAS  Google Scholar 

  53. Bocelli-Tyndall C, Barbero A, Candrian C et al (2006) Human articular chondrocytes suppress in vitro proliferation of anti-CD3 activated peripheral blood mononuclear cells. J Cell Physiol 209:732–734

    Article  PubMed  CAS  Google Scholar 

  54. Nemeth K, Keane-Myers A, Brown JM et al (2010) Bone marrow stromal cells use TGF-beta to suppress allergic responses in a mouse model of ragweed-induced asthma. Proc Natl Acad Sci 107:5652–5657

    Article  PubMed  PubMed Central  Google Scholar 

  55. Zhao S, Wehner R, Bornhañuser M et al (2010) Immunomodulatory properties of mesenchymal stromal cells and their therapeutic consequences for immune-mediated disorders. Stem Cells Dev 19:607–614

    Article  PubMed  CAS  Google Scholar 

  56. Wagner J, Kean T, Young R et al (2009) Optimizing mesenchymal stem cell-based therapeutics. Curr Opin Biotechnol 20:531–536

    Article  PubMed  CAS  Google Scholar 

  57. Ko IK, Kim BG, Awadallah A et al (2010) Targeting improves MSC treatment of inflammatory bowel disease. Mol Ther 18:1365–1372

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Lim PK, Patel SA, Gregory LA et al (2010) Neurogenesis: role for microRNAs and mesenchymal stem cells in pathological states. Curr Med Chem 17:2159–2167

    Article  PubMed  CAS  Google Scholar 

  59. Richardson SM, Hoyland JA, Mobasheri R et al (2010) Mesenchymal stem cells in regenerative medicine: opportunities and challenges for articular cartilage and intervertebral disc tissue engineering. J Cell Physiol 222:23–32

    Article  PubMed  CAS  Google Scholar 

  60. da Silva ML, Caplan AI, Nardi NB (2008) In search of the in vivo identity of mesenchymal stem cells. Stem Cells 26:2287–2299

    Article  Google Scholar 

  61. Greco SJ, Rameshwar P (2007) Enhancing effect of IL-1 on neurogenesis from adult human mesenchymal stem cells: implication for inflammatory mediators in regenerative medicine. J Immunol 179:3342–3350

    Article  PubMed  CAS  Google Scholar 

  62. Schinkothe T, Bloch W, Schmidt A (2008) In vitro secreting profile of human mesenchymal stem cells. Stem Cells Dev 17:199–206

    Article  PubMed  CAS  Google Scholar 

  63. Chan JL, Tang KC, Patel AP et al (2006) Antigen-presenting property of mesenchymal stem cells occurs during a narrow window at low levels of interferon-gamma. Blood 107:4817–4824

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Campeau PM, Rafei M, Francois M et al (2008) Mesenchymal stromal cells engineered to express erythropoietin induce anti-erythropoietin antibodies and anemia in allorecipients. Mol Ther 17:369–372

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Heng BC, Cowan CM, Davalian D et al (2009) Electrostatic binding of nanoparticles to mesenchymal stem cells via high molecular weight polyelectrolyte chains. J Tissue Eng Regen Med 3:243–254

    Article  PubMed  CAS  Google Scholar 

  66. Romieu-Mourez R, Francois M, Boivin MN et al (2007) Regulation of MHC class II expression and antigen processing in murine and human Mesenchymal stromal cells by IFN-{gamma}, TGF-beta, and cell density. J Immunol 179:1549–1558

    Article  PubMed  CAS  Google Scholar 

  67. Pistoia V, Raffaghello L (2010) Potential of mesenchymal stem cells for the therapy of autoimmune diseases. Expert Rev Clin Immunol 6:211–218

    Article  PubMed  CAS  Google Scholar 

  68. Rameshwar P, Qiu H, Vatner SF (2010) Stem cells in cardiac repair in an inflammatory microenvironment. Minerva Cardioangiol 58:127–146

    PubMed  CAS  Google Scholar 

  69. Patel SA, Sherman L, Munoz J et al (2008) Immunological properties of mesenchymal stem cells and clinical implications. Arch Immunol Ther Exp 56:1–8

    Article  CAS  Google Scholar 

  70. Kim J, Hematti P (2009) Mesenchymal stem cell-educated macrophages: a novel type of alternatively activated macrophages. Exp Hematol 37:1445–1453

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Dominici M, Le BK, Mueller I et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317

    Article  PubMed  CAS  Google Scholar 

  72. Dominici M, Paolucci P, Conte P et al (2009) Heterogeneity of multipotent mesenchymal stromal cells: from stromal cells to stem cells and vice versa. Transplantation 87:S36–S42

    Article  PubMed  Google Scholar 

  73. Fujiwara N, Kobayashi K (2005) Macrophages in inflammation. Curr Drug Targets Inflamm Allergy 4:281–286

    Article  PubMed  CAS  Google Scholar 

  74. Pfeifer JD, Wick MJ, Roberts RL et al (1993) Phagocytic processing of bacterial antigens for class I MHC presentation to T cells. Nature 361:359–362

    Article  PubMed  CAS  Google Scholar 

  75. Stagg J (2007) Immune regulation by mesenchymal stem cells: two sides to the coin. Tissue Antigens 69:1–9

    Article  PubMed  CAS  Google Scholar 

  76. Herrero C, Sebastian C, Marquqs L et al (2002) Immunosenescence of macrophages: reduced MHC class II gene expression. Exp Gerontol 37:389–394

    Article  PubMed  CAS  Google Scholar 

  77. Tang KC, Trzaska KA, Smirnov S et al (2008) Down-regulation of MHC-II in mesenchymal stem cells at high IFN- can be partly explained by cytoplasmic retention of CIITA. J Immunol 180:1826–1833

    Article  PubMed  CAS  Google Scholar 

  78. Castillo MD, Trzaska KA, Greco SJ et al (2008) Immunostimulatory effects of mesenchymal stem cell-derived neurons: implications for stem cell therapy in allogeneic transplantations. Clin Transl Sci 1:27–34

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Allan SM, Tyrrell PJ, Rothwell NJ (2005) Interleukin-1 and neuronal injury. Nat Rev Immunol 5:629–640

    Article  PubMed  CAS  Google Scholar 

  80. Laver J, Moore MAS (1989) Clinical use of recombinant human hematopoietic growth factors. J Natl Cancer Inst 81:1370–1382

    Article  PubMed  CAS  Google Scholar 

  81. Moore MA (2002) Cytokine and chemokine networks influencing stem cell proliferation, differentiation, and marrow homing. J Cell Biochem Suppl 38:29–38

    Article  PubMed  CAS  Google Scholar 

  82. Bagby GC (1989) Interleukin-1 and hematopoiesis. Blood Rev 3:152–161

    Article  PubMed  Google Scholar 

  83. Dinarello CA (1996) Biologic basis for interleukin-1 in disease. Blood 87:2095–2147

    PubMed  CAS  Google Scholar 

  84. Dinarello CA (2005) Blocking IL-1 in systemic inflammation. J Exp Med 201:1355–1359

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Roberts AB, Sporn MB (1993) Physiological actions and clinical applications of transforming growth factor-beta (TGF-beta). Growth Factors 8:1–9

    Article  PubMed  CAS  Google Scholar 

  86. Massague J, Andres J, Attisano L et al (1992) TGF-beta receptors. Mol Reprod Dev 32:99–104

    Article  PubMed  CAS  Google Scholar 

  87. Massague J, Weis-Garcia F (1996) Serine/threonine kinase receptors: mediators of transforming growth factor beta family signals. Cancer Surv 27:41–64

    PubMed  CAS  Google Scholar 

  88. Shi Y, Massague J (2003) Mechanisms of TGF-[beta] signaling from cell membrane to the nucleus. Cell 113:685–700

    Article  PubMed  CAS  Google Scholar 

  89. Wrana JL (2000) Regulation of Smad activity. Cell 100:189–192

    Article  PubMed  CAS  Google Scholar 

  90. Massague J, Wotton D (2000) Transcriptional control by the TGF-beta/Smad signaling system. EMBO J 19:1745–1754

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Mehra A, Wrana JL (2002) TGF-beta and the Smad signal transduction pathway. Biochem Cell Biol 80:605–622

    Article  PubMed  CAS  Google Scholar 

  92. Sato M, Muragaki Y, Saika S et al (2003) Targeted disruption of TGF-beta1/Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction. J Clin Invest 112(10):1486–1494

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Golestaneh N, Mishra B (2005) TGF-beta, neuronal stem cells and glioblastoma. Oncogene 24:5722–5730

    Article  PubMed  CAS  Google Scholar 

  94. Downing JR (2004) TGF-{beta} signaling, tumor suppression, and acute lymphoblastic leukemia. N Engl J Med 351:528–530

    Article  PubMed  CAS  Google Scholar 

  95. Sokol JP, Schiemann WP (2004) Cystatin C antagonizes transforming growth factor {beta} signaling in normal and cancer cells. Mol Cancer Res 2:183–195

    PubMed  CAS  Google Scholar 

  96. Kim SJ, Letterio J (2003) Transforming growth factor-beta signaling in normal and malignant hematopoiesis. Leukemia 17:1731–1737

    Article  PubMed  CAS  Google Scholar 

  97. Tracey D, Klareskog L, Sasso EH et al (2008) Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther 117(2):244–279

    Article  PubMed  CAS  Google Scholar 

  98. Locksley RM, Killeen N, Lenardo MJ (2001) The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104:487–501

    Article  PubMed  CAS  Google Scholar 

  99. Romieu-Mourez R, Francois M, Boivin MN et al (2009) Cytokine modulation of TLR expression and activation in mesenchymal stromal cells leads to a proinflammatory phenotype. J Immunol 182:7963–7973

    Article  PubMed  CAS  Google Scholar 

  100. van den Berk LCJ, Jansen BJH, Siebers-Vermeulen KGC et al (2009) Mesenchymal stem cells respond to TNF but do not produce TNF. J Leukoc Biol 87:283–289

    Article  PubMed  CAS  Google Scholar 

  101. Fu X, Han B, Cai S et al (2009) Migration of bone marrow-derived mesenchymal stem cells induced by tumor necrosis factor-alpha and its possible role in wound healing. Wound Repair Regen 17:185–191

    Article  PubMed  Google Scholar 

  102. Kim YS, Park HJ, Hong MH et al (2009) TNF-alpha enhances engraftment of mesenchymal stem cells into infarcted myocardium. Front Biosci 14:2845–2856

    Article  CAS  Google Scholar 

  103. Kim VN (2005) MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol 6(5):376–385

    Article  PubMed  CAS  Google Scholar 

  104. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  PubMed  CAS  Google Scholar 

  105. Kim J, Krichevsky A, Grad Y et al (2004) Identification of many microRNAs that copurify with polyribosomes in mammalian neurons. Proc Natl Acad Sci 101:360–365

    Article  PubMed  CAS  Google Scholar 

  106. Zamore PD, Haley B (2005) Ribo-gnome: the big world of small RNAs. Science 309(5740):1519–1524

    Article  PubMed  CAS  Google Scholar 

  107. Chen CZ, Li L, Lodish HF et al (2004) MicroRNAs modulate hematopoietic lineage differentiation. Science 303:83–86

    Article  PubMed  CAS  Google Scholar 

  108. Harfe BD (2005) MicroRNAs in vertebrate development. Curr Opin Genet Dev 15:410–415

    Article  PubMed  CAS  Google Scholar 

  109. Ramkissoon SH, Mainwaring LA, Ogasawara Y et al (2006) Hematopoietic-specific microRNA expression in human cells. Leuk Res 30:643–647

    Article  PubMed  CAS  Google Scholar 

  110. Greco SJ, Rameshwar P (2007) miRNAs regulate synthesis of the neurotransmitter substance P in human mesenchymal stem cell-derived neuronal cells. Proc Natl Acad Sci U S A 104:15484–15489

    Article  PubMed  PubMed Central  Google Scholar 

  111. Miska E, varez-Saavedra E, Townsend M et al (2004) Microarray analysis of microRNA expression in the developing mammalian brain. Genome Biol 5:R68

    Article  PubMed  PubMed Central  Google Scholar 

  112. Schaefer A, O’Carroll D, Tan CL et al (2007) Cerebellar neurodegeneration in the absence of microRNAs. J Exp Med 204:1553–1558

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  113. Kobayashi M, Fitz L, Ryan M et al (1989) Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. J Exp Med 170:827–845

    Article  PubMed  CAS  Google Scholar 

  114. Kang HS, Habib M, Chan J et al (2005) A paradoxical role for IFN-[gamma] in the immune properties of mesenchymal stem cells during viral challenge. Exp Hematol 33:796–803

    Article  PubMed  CAS  Google Scholar 

  115. Stark GR, Kerr IM, Williams BRG et al (1998) How cells respond to interferons. Annu Rev Biochem 67:227–264

    Article  PubMed  CAS  Google Scholar 

  116. Ahmed CMI, Burkhart MA, Mujtaba MG et al (2003) The role of IFN{gamma} nuclear localization sequence in intracellular function. J Cell Sci 116:3089–3098

    Article  PubMed  CAS  Google Scholar 

  117. Subramaniam PS, Green MM, Larkin J III et al (2001) Nuclear translocation of IFN-gamma is an intrinsic requirement for its biologic activity and can be driven by a heterologous nuclear localization sequence. J Interf Cytokine Res 21:951–959

    Article  CAS  Google Scholar 

  118. Subramaniam PS, Johnson HM (2004) The IFNAR1 subunit of the type I IFN receptor complex contains a functional nuclear localization sequence. FEBS Lett 578:207–210

    Article  PubMed  CAS  Google Scholar 

  119. Bergmann CC, Parra B, Hinton DR et al (2003) Perforin-mediated effector function within the central nervous system requires IFN-{gamma}-mediated MHC up-regulation. J Immunol 170:3204–3213

    Article  PubMed  CAS  Google Scholar 

  120. Boss JM (1997) Regulation of transcription of MHC class II genes. Curr Opin Immunol 9:107–113

    Article  PubMed  CAS  Google Scholar 

  121. English K, Barry FP, Mahon BP (2008) Murine mesenchymal stem cells suppress dendritic cell migration, maturation and antigen presentation. Immunol Lett 115(1):50–58

    Article  PubMed  CAS  Google Scholar 

  122. English K, Ryan JM, Tobin L et al (2009) Cell contact, prostaglandin E(2) and transforming growth factor beta 1 play non-redundant roles in human mesenchymal stem cell induction of CD4+CD25(high) forkhead box P3+ regulatory T cells. Clin Exp Immunol 156:149–160

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  123. Polchert D, Sobinsky J, Douglas G et al (2008) IFN-gamma activation of mesenchymal stem cells for treatment and prevention of graft versus host disease. Eur J Immunol 38:1745–1755

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  124. Capitini CM, Herby S, Milliron M et al (2009) Bone marrow deficient in IFN-{gamma} signaling selectively reverses GVHD-associated immunosuppression and enhances a tumor-specific GVT effect. Blood 113:5002–5009

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  125. DelaRosa O, Lombardo E, Beraza A et al (2009) Requirement of IFN-gamma-mediated Indoleamine 2,3-Dioxygenase expression in the modulation of lymphocyte proliferation by human adipose-derived stem cells. Tissue Eng A 15:2795–2806

    Article  CAS  Google Scholar 

  126. Francois M, Romieu-Mourez R, Stock-Martineau S et al (2009) Mesenchymal stromal cells cross-present soluble exogenous antigens as part of their antigen-presenting cell properties. Blood 114(13):2632–2638

    Article  PubMed  CAS  Google Scholar 

  127. Coulson JM (2005) Transcriptional regulation: cancer, neurons and the REST. Curr Biol 15:R665–R668

    Article  PubMed  CAS  Google Scholar 

  128. Belyaev ND, Wood IC, Bruce AW et al (2004) Distinct RE-1 silencing transcription factor-containing complexes interact with different target genes. J Biol Chem 279:556–561

    Article  PubMed  CAS  Google Scholar 

  129. Bruce AW, Donaldson IJ, Wood IC et al (2004) Genome-wide analysis of repressor element 1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) target genes. Proc Natl Acad Sci 101:10458–10463

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  130. Fiskerstrand CE, Newey P, McGregor GP et al (2000) A role for Octamer binding protein motifs in the regulation of the proximal preprotachykinin-A promoter. Neuropeptides 34:348–354

    Article  PubMed  CAS  Google Scholar 

  131. Quinn JP, Bubb VJ, Marshall-Jones ZV et al (2002) Neuron restrictive silencer factor as a modulator of neuropeptide gene expression. Regul Pept 108:135–141

    Article  PubMed  CAS  Google Scholar 

  132. Su X, Kameoka S, Lentz S et al (2004) Activation of REST/NRSF target genes in neural stem cells is sufficient to cause neuronal differentiation. Mol Cell Biol 24:8018–8025

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  133. Wood IC, Belyaev ND, Bruce AW et al (2003) Interaction of the repressor element 1-silencing transcription factor (REST) with target genes. J Mol Biol 334:863–874

    Article  PubMed  CAS  Google Scholar 

  134. Yeo M, Lee SK, Lee B et al (2005) Small CTD phosphatases function in silencing neuronal gene expression. Science 307:596–600

    Article  PubMed  CAS  Google Scholar 

  135. Greenway DJ, Street M, Jeffries A et al (2007) RE1 silencing transcription factor maintains a repressive chromatin environment in embryonic hippocampal neural stem cells. Stem Cells 25:354–363

    Article  PubMed  CAS  Google Scholar 

  136. Sun YM, Greenway DJ, Johnson R et al (2005) Distinct profiles of REST interactions with its target genes at different stages of neuronal development. Mol Biol Cell 16:5630–5638

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  137. Zhang P, Pazin MJ, Schwartz CM et al (2008) Nontelomeric TRF2-REST interaction modulates neuronal gene silencing and fate of tumor and stem cells. Curr Biol 18:1489–1494

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  138. Nahas GR, Murthy RG, Patel SA et al (2016) The RNA-binding protein Musashi 1 stabilizes the oncotachykinin 1 mRNA in breast cancer cells to promote cell growth. FASEB J 30:149–159

    Article  PubMed  CAS  Google Scholar 

  139. Thakore-Shah K, Koleilat T, Jan M et al (2015) REST/NRSF knockdown alters survival, lineage differentiation and signaling in human embryonic stem cells. PLoS One 10(12):e0145280

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  140. Trosko JE (2006) From adult stem cells to cancer stem cells: Oct-4 gene, cell-cell communication, and hormones during tumor promotion. Ann N Y Acad Sci 1089:36–58

    Article  PubMed  CAS  Google Scholar 

  141. Greco SJ, Smirnov S, Rameshwar P (2007) Synergy between RE-1 silencer of transcription (REST) and NFêB in the repression of the neurotransmitter gene Tac1 in human mesenchymal stem cells: Implication for microenvironmental influence on stem cell therapies. J Biol Chem 282:30039–30050

    Article  PubMed  CAS  Google Scholar 

  142. Weissman AM (2008) How much REST is enough? Cancer Cell 13:381–383

    Article  PubMed  CAS  Google Scholar 

  143. Majumder S (2006) REST in good times and bad: roles in tumor suppressor and oncogenic activities. Cell Cycle 5:1929–1935

    Article  PubMed  CAS  Google Scholar 

  144. Reddy BY, Greco SJ, Patel PS et al (2009) RE-1-Çosilencing transcription factor shows tumor-suppressor functions and negatively regulates the oncogenic TAC1 in breast cancer cells. Proc Natl Acad Sci 106:4408–4413

    Article  PubMed  PubMed Central  Google Scholar 

  145. Conaco C, Otto S, Han JJ et al (2006) Reciprocal actions of REST and a microRNA promote neuronal identity. Proc Natl Acad Sci 103:2422–2427

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  146. Kim SM, Yang JW, Park MJ et al (2006) Regulation of human tyrosine hydroxylase gene by neuron-restrictive silencer factor. Biochem Biophys Res Commun 346:426–435

    Article  PubMed  CAS  Google Scholar 

  147. Perrier AL, Studer L (2003) Making and repairing the mammalian brain – in vitro production of dopaminergic neurons. Semin Cell Dev Biol 14:181–189

    Article  PubMed  CAS  Google Scholar 

  148. Lange KW, Mecklinger L, Walitza S et al (2006) Brain dopamine and kinematics of graphomotor functions. Hum Mov Sci 25:492–509

    Article  PubMed  Google Scholar 

  149. Trzaska KA, Rameshwar P (2007) Current advances in the treatment of Parkinson’s disease with stem cells. Curr Neurovas Res 4:99–109

    Article  CAS  Google Scholar 

  150. Shigetomi S, Fukuchi S (1994) Recent aspect of the role of peripheral dopamine and its receptors in the pathogenesis of hypertension. Fukushima J Med Sci 40:69–83

    PubMed  CAS  Google Scholar 

  151. Tansey MG, McCoy MK, Frank-Cannon TC (2007) Neuroinflammatory mechanisms in Parkinson’s disease: potential environmental triggers, pathways, and targets for early therapeutic intervention. Exp Neurol 208:1–25

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  152. Sanberg PR (2007) Neural stem cells for Parkinson’s disease: to protect and repair. PNAS 104:11869–11870

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  153. Blanc KL, Pittenger MF (2005) Mesenchymal stem cells: progress toward promise. Cytotherapy 7:36–45

    Article  PubMed  Google Scholar 

  154. Gregory CA, Ylostalo J, Prockop DJ (2005) Adult bone marrow stem/progenitor cells (MSCs) are preconditioned by microenvironmental “niches” in culture: a two-stage hypothesis for regulation of MSC fate. Sci STKE 2005:e37

    Google Scholar 

  155. Honma T, Honmou O, Iihoshi S et al (2006) Intravenous infusion of immortalized human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat. Exp Neurol 199:56–66

    Article  PubMed  CAS  Google Scholar 

  156. Shyu WC, Lee YJ, Liu DD et al (2006) Homing genes, cell therapy and stroke. Front Biosci 11:899–907

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work is supported by a grant awarded by F.M Kirby Foundation.

Author information

Authors and Affiliations

  1. Department of Medicine-Hematology/Oncology, Rutgers New Jersey Medical School, Newark, NJ, USA

    Pranela Rameshwar

  2. Division of Hematology/Oncology, Department of Medicine, University of Medicine and Dentistry of New Jersey-Rutgers—New Jersey Medical School, Newark, NJ, USA

    Caitlyn A. Moore & Caroline P. Smith

  3. Division of Hematology/Oncology, Department of Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ, USA

    Niloy N. Shah

Authors
  1. Pranela Rameshwar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Caitlyn A. Moore
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Niloy N. Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Caroline P. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pranela Rameshwar .

Editor information

Editors and Affiliations

  1. Basic Research Laboratory, Stem Cell Regulation and Animal Aging Section, National Cancer Institute, Frederick, MD, USA

    Shree Ram Singh

  2. Department of Medicine-Hematology/Oncology, Rutgers New Jersey Medical School, Newark, NJ, USA

    Pranela Rameshwar

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Rameshwar, P., Moore, C.A., Shah, N.N., Smith, C.P. (2018). An Update on the Therapeutic Potential of Stem Cells. In: Singh, S., Rameshwar, P. (eds) Somatic Stem Cells. Methods in Molecular Biology, vol 1842. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8697-2_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-8697-2_1

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8696-5

  • Online ISBN: 978-1-4939-8697-2

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation