Immunogenicity of Stem Cells

Immunogenicity of Stem Cells

Franz Ricklefs (University Heart Center Hamburg, Germany) and Sonja Schrepfer (University Heart Center Hamburg, Germany)
DOI: 10.4018/978-1-4666-2506-8.ch005
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Current medical research is focused on two particular types of stem cells, adult stem cells and embryonic stem cells. Both cell types demonstrate a tremendous potential as the source for regenerative medicine due to their paracrine and pluripotency effects, respectively. Therefore, stem cells are expected to have an enormous impact on clinical therapy. However, allogeneic approaches using “off-the-shelf” stem cells from healthy donors are the only financially and ethically feasible pathway. The long-standing assumption that stem cells are not recognized by the recipient’s immune system was recently disproved not only by our group. Therefore, specific knowledge of the immunologic properties of pluripotent and multipotent stem cells is a prerequisite for safe applications of stem cell-based therapy. This chapter will discuss the involvement of the innate and adaptive immune system and summarize state-of-the art approaches to overcome the immunological barrier.
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In December 1905 the early days of modern medicine began with the first reported tissue transplantation (cornea transplantation) performed in Olmutz, Moravia (now Czech Republic). Around 5 decades later the first milestone in organ transplantation had been established when a team of physicians in Boston, USA, performed the first successful kidney transplantation ever reported. Since these early days, immune rejection of the transplanted tissue had been known, except when performed between identical twins. Due to extensive research efforts, scientists have revealed that the differences in itLA proteins between allogeneic (genetically not-identical) individuals trigger the rejection by an immunocompetent host. Large diverse groups of molecules involved in immune recognition were discovered and defined as histocompatibility antigens, divided into three groups: 1) Major Histocompatibility Complex (MHC) molecules, in humans: Human Lymphocyte Antigen (HLA); 2) minor Histocompatibility complex Antigens (mHAgs); 3) ABO blood group antigens (Tang & Drukker, 2011). Hence, even nowadays, an immunosuppressive therapy is still mandatory and is included in protocols when organs or tissues are transplanted between allogeneic individuals.

Since transplantation medicine started, it became crucial to overcome the lack of available organs needed due to the high number of patients, waiting on the organ-lists all over the world. To overcome this hurdle a novel strategy was offered when Embryonic Stem Cells (ESCs) had been first isolated (murine ESC in 1981 [Kaufman, Robertson, Handyside, & Evans, 1983]; human in 1994 [Bongso, Fong, Ng, & Ratnam, 1994]) and also their adult partners, Adult Stem Cells (ASCs) with the first bone marrow transplantation in a 2-year old patient with Wiskott Aldrich syndrome (Bach, Albertini, Joo, Anderson, & Bortin, 1968). Their directed differentiation into a variety of tissue specific cell types seemed and still seems very appealing for organ restoration and cell-based therapies. However, up to today a successful transfer of the therapeutic promises of ESCs into the clinic is absent. Undefined growth of ESCs leading to teratoma formation (Figure 1) and immune rejection of transplanted ESCs are still major problems that need to be resolved before a successful clinical translation can be made. Therefore, current medicine is not only focused on ESCs but rather on ASCs, since they are already tissue-specific and lack the ability to form a teratoma. Nevertheless, an allogeneic approach for ASCs-therapy leads to a rejection of the transplanted cells by an immunocompetent recipient.

Figure 1.

Verification of pluripotency of ESCs by teratoma formation in vivo. Teratoma formation seven weeks after injection of 1x106 pluripotent ESCs into SCID beige mice. Teratomas are stained with germlayer specific antibodies and visualized using confocal microscopy. Cell nuclei are stained in blue (DAPI); A: green = Cytokeratin 8 indicating the endodermal cell lineage; B: far red = GFAP identifying ektodermal cell types; C: yellow = Brachyury indentifying mesenchymal derived cell types; D: merged (magnification: 400x). (Courtesy of Xiaoqin Hua.)

The purpose of this book chapter is to reveal the current knowledge of the involvement of the innate and adaptive immune system and to summarize state-of-the art approaches to overcome the immunological barrier.

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Editorial Advisory Board
Table of Contents
James Adjaye
Andriani Daskalaki
Chapter 1
Julia Zimmer, Elisa Degenkolbe, Britt Wildemann, Petra Seemann
More than 40 years after the discovery of Bone Morphogenetic Proteins (BMPs) as bone inducers, a whole protein family of growth factors connected to... Sample PDF
BMP Signaling in Regenerative Medicine
Chapter 2
George I. Lambrou, Maria Adamaki, Apostolos Zaravinos
There is an increasing tendency to use stem cells as potential therapeutics in various human diseases. This is a rapidly progressing field, believed... Sample PDF
Proliferation and Regeneration: Methodologies in Cancer Treatment and Post-Treatment Tissue Reconstruction
Chapter 3
Svetoslav Nikolov, Mukhtar Ullah, Momchil Nenov, Julio Vera Gonzalez, Peter Raasch, Olaf Wolkenhauer
Mathematical modeling is increasingly used to improve our understanding of colorectal cancer. In the first part of this chapter, the authors give a... Sample PDF
Modeling Colorectal Cancer: A Stability Analysis Approach
Chapter 4
Ana M. Sotoca, Michael Weber, Everardus J. J. van Zoelen
Human mesenchymal stem cells have a high potential in regenerative medicine. They can be isolated from a variety of adult tissues, including bone... Sample PDF
Gene Expression Regulation underlying Osteo-, Adipo-, and Chondro-Genic Lineage Commitment of Human Mesenchymal Stem Cells
Chapter 5
Franz Ricklefs, Sonja Schrepfer
Current medical research is focused on two particular types of stem cells, adult stem cells and embryonic stem cells. Both cell types demonstrate a... Sample PDF
Immunogenicity of Stem Cells
Chapter 6
Sonja Schallenberg, Cathleen Petzold, Julia Riewaldt, Karsten Kretschmer
CD4+CD25+ regulatory T (Treg) cells expressing the forkhead box transcription factor Foxp3 have a vital function in the maintenance of immune... Sample PDF
Regulatory T Cell-Based Immunotherapy: Prospects of Antigen-Specific Tolerance Induction
Chapter 7
Ali Mobasheri
This chapter reviews the structure and function of articular cartilage and the pathogenesis of Osteoarthritis (OA) before exploring the challenges... Sample PDF
Regeneration of Articular Cartilage: Opportunities, Challenges, and Perspectives
Chapter 8
Frank Martin, Mario Lehmann, Ursula Anderer
Since our society is characterized by an increasing age of its people on the one hand and a high number of persons dealing with sports on the other... Sample PDF
Generation of Scaffold Free 3-D Cartilage-Like Microtissues from Human Chondrocytes
Chapter 9
The Hidden Markov Brains  (pages 195-214)
Tuan D. Pham
This chapter presents Hidden Markov models (HMM) of the brain on Magnetic Resonance Imaging (MRI) for the inference of white matter hyperintensities... Sample PDF
The Hidden Markov Brains
Chapter 10
Arghya Paul
The breakthrough technologies of stent have revolutionized the medical industry, particularly in the field of percutaneous coronary interventions... Sample PDF
Designing Biomedical Stents for Vascular Therapy: Current Perspectives and Future Promises
Chapter 11
Yos Morsi, Zhang Li, Sheng Wang
This chapter gives an overview of heart valve diseases, their diagnostics techniques, and current and future treatments with particular emphasis on... Sample PDF
Heart Valve Diseases in the Elderly: Current Treatments and Future Directions
Chapter 12
Olof A. Lindahl, Anders Eklund, Per Hallberg
The chapter involves the description and the application of a new sensor technology called tactile resonance sensors for diagnoses of the... Sample PDF
Tactile Resonance Sensors for Detection and Diagnosis of Age-Related Diseases
Chapter 13
Athina Bakopoulou, Gabriele Leyhausen, Werner Geurtsen, Petros Koidis
Stem cell-based dental tissue regeneration is a new and exciting field that has the potential to transform the way that we practice dentistry. It... Sample PDF
Dental Tissue Engineering Research and Translational Approaches towards Clinical Application
Chapter 14
Phuc Van Pham, Loan Thi-Tung Dang, Nhung Hai Truong, Ngoc Kim Phan
In recent years, Platelet Rich Plasma (PRP) and Adipose-Derived Stem Cells (ADSCs) have been used separately for many clinical applications... Sample PDF
Can Activated Platelet Rich Plasma Combined with Adipose-Derived Stem Cells Be Used to Treat Skin Wrinkles?: A Mechanism Study
Appendix A
Appendix B
Appendix C
Appendix D
Appendix E
Appendix F
Appendix G
Appendix H
Appendix I
About the Contributors