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Erdal Karaoz* |
Center for Stem Cell and Gene Therapies, Research and Practice, Institute of Health Sciences, Stem Cell Department, Kocaeli University, Umuttepe-Izmit, Kocaeli, Turkey |
Corresponding Author : |
Dr. Erdal Karaoz Ph.D
Center for Stem Cell and Gene Therapies
Research and Practice, Institute of Health Sciences
Stem Cell Department, Kocaeli University
Umuttepe-Izmit, Kocaeli, Turkey
Tel: +(90) 262 3038685
E-mail: [email protected] |
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Received November 29, 2013; Accepted November 30, 2013; Published December 02, 2013 |
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Citation: Karaoz E (2013) The Role of Mesenchymal Stem Cells in Organ Transplantation Immunomodulatory and Anti-inflammatory Properties of Mesenchymal Stem Cells for Application in Organ Transplantation. J Transplant Technol Res 4:e128.
doi:
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Copyright: © 2013 Karaoz E. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
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Journal of Transplantation Technologies & Research |
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As a clinical practice, transplantation is a strategy for overcoming
disease that could not be readily curable by any existing therapies. The
scarcity of the organ number for transplantation in the continuously
growing population makes the overall picture critical for meeting
the requirement. The prevention of organ rejection, which is caused
by the destruction of transplanted tissue by the tissue recipient’s
(host) immune system, is mainly focused in routine application.
The immunosuppressive drugs provide some benefits against organ
rejection, but the immune system with its factors is still a major obstacle
in successful transplantation. |
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The crucial role of mesenchymal stem cells in tissue function is
widely known of their effect on the tissue components by paracrine
and autocrine factors. Until the last decades, the self-renewal capacity
and multi-lineage differentiation potency of these cells were mainly
focused for the tissue regeneration applications. On the other hand,
the chemical factors secreted by mesenchymal stem cells can promote
differentiation of stem cells and tissue remodelling, but they can also
affect the immune system by suppressing maturation of Dendritic Cells
(DCs) and the functions of T cells, B cells and Natural Killer (NK) cells,
as well as by inducing regulatory T (Treg) cells. The immunoregulatory
effects of MSCs have been shown in otoimmune diseases such as Graft
Versus Host Disease (GVHD), osteogenesis imperfecta, arthiritis,
encephalomyelitis [1,2]. The allo-reactivity caused by the immune
system is prevented by use of immunosuppressive drug, which might
lead severe side effect. The use of mesenchymal stem cells could be
considered as an alternative approach to control the immune response
in clinical transplantation settings. |
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Combined with the immunosuppressive therapy, MSCs
administrations following transplantation were shown to prolong
cardiac allograft survival, and attenuate graft rejection earlier [3].
MSCs together with low dose of drug treatment improved the donorspecific
graft tolerance and reduce the immune response in this case.
Similar studies also provide supportive results that MSCs enhance both
transplant acceptance and physiologic functions [4]. The development of
ischemia then reperfusion occur following kidney transplantation. This
leads the formation of reactive oxygen species and lipid peroxidation.
Thus, necrosis and apoptosis rates escalate in tissue in parallel with the
intensifying inflammation. Consequently, tissue destruction is followed
by the organ rejection [5]. In the MSC treatment with conventional
immune suppressing drug therapy after the kidney transplantation, the
IL-2 mediated role has been shown in recent study [6]. The point of use
the immunosuppressive drugs is the control of inflammation and the
inhibition of transplant rejection triggered by the immune system. Treg
cells are the important regulatory components of the immune system,
the function of which was inhibited by inflammatory cytokines, like
IL-1β, IL-2, IL-6 and TNFα. In response to down-regulation of Treg
activity, the attack of cytotoxic T-cells against the transplanted tissue
surge significantly [7]. The regulation of the cytokine expression by
MSCs mainly provides the control over immune response. |
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The role of MSCs in transplantations is not limited only with the regeneration and anti-inflammatory effect, but the prevention
of fibrosis is well-recognized in the studies involving solid organ
transplantation. The anti-inflammatory factors, including IL1ra, TGFb,
Hepatocyte Growth Factor (HGF), nitric oxide (NO) and HLA-G,
secreted by MSCs were also shown to function in reduce fibrosis in the
heart [8], and other organs such as the lung, liver, and kidney [9-12] in
the experimental animal models. The attenuated fibrosis level in tissue
engraft will also reduce the rejection by MSC treatment [13]. |
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MSCs might be accepted as an attractive cell immunotherapy tool
in cell and organ transplantation. In addition to their regenerative
potential, immunosuppressive effects of MSCs could participate in the
successful organ grafting and regeneration of the transplanted organ.
Some recent reports provided the evidences for their support in the
engrafted tissue by multiple paths, but additional knowledge and welldesigned
studies are required to understand their effect on the immune
system before clinical applications. |
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References |
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- Demircan PC, Sariboyaci AE, and Karaoz E (2013) Immunoregulatory Properties of Mesenchymal Stem Cells: In Vitro and In Vivo. Turksen K (ed.) Stem Cells: Current Challenges and New Directions, Stem Cell Biology and Regenerative Medicine 33, Springer Science Business Media, New York, USA.
- Karaoz E, Akpinar B (2013) Filling the Gap in the Relationship between Cancer and Stem Cells. Turksen K (ed.) Stem Cells: Current Challenges and New Directions, Stem Cell Biology and Regenerative Medicine 33, Springer Science Business Media, New York, USA.
- Ge W, Jiang J, Baroja ML, Arp J, Zassoko R, et al. (2009) Infusion of mesenchymal stem cells and rapamycin synergize to attenuate alloimmune responses and promote cardiac allograft tolerance. Am J Transplant 9: 1760-1772.
- Crop, MJ, Baan CC, Korevaar SS, Ijzermans JN, Alwayn IP, et al. (2009) Donor-derived mesenchymal stem cells suppress alloreactivity of kidney transplant patients. Transplantation 87: 896-906.
- Silverstein DM (2009) Inflammation after renal transplantation: Role in the development of graft dysfunction and potential therapies. Journal and Organ Dysfunction 5: 233-241.
- Tan J, Wu W, Xu X, Liao L, Zheng F, et al. (2012) Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: a randomized controlled trial. JAMA 307: 1169-1177.
- Hanidziar D, Koulmanda M, Strom TB (2010) Creating transplant tolerance by taming adverse intragraft innate immunity. F1000 Biol Rep 2: 83.
- Ohnishi S, Sumiyoshi H, Kitamura S, Nagaya N (2007) Mesenchymal stem cells attenuate cardiac fibroblast proliferation and collagen synthesis through paracrine actions. FEBS Lett 581: 3961-3966.
- Ninichuk V, Gross O, Segerer S, Hoffmann R, Radomska E, et al. (2006) Multipotent mesenchymal stem cells reduce interstitial fibrosis but do not delay progression of chronic kidney disease in collagen4A3-deficient mice. Kidney Int 70: 121-129.
- Ortiz LA, Gambelli F, McBride C, McBride C, Gaupp D, et al. (2003) Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci U S A 100: 8407-8411.
- Rojas M, Xu J, Woods CR, Mora AL, Spears W, et al. (2005) Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol 33: 145-152.
- Yilmaz S, Inandiklioglu N, Yildizdas D, Subasi C, Acikalin A, et al. (2013) Mesenchymal stem cell: does it work in an experimental model with acute respiratory distress syndrome? Stem Cell Rev 9: 80-92.
- Reinders ME, Rabelink TJ, de Fijter JW (2013) The role of mesenchymal stromal cells in chronic transplant rejection after solid organ transplantation. Curr Opin Organ Transplant 18: 44-50.
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References
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- Demircan PC, Sariboyaci AE, and Karaoz E (2013) Immunoregulatory Properties of Mesenchymal Stem Cells: In Vitro and In Vivo. Turksen K (ed.) Stem Cells: Current Challenges and New Directions, Stem Cell Biology and Regenerative Medicine 33, Springer Science Business Media, New York, USA.
- Karaoz E, Akpinar B (2013) Filling the Gap in the Relationship between Cancer and Stem Cells. Turksen K (ed.) Stem Cells: Current Challenges and New Directions, Stem Cell Biology and Regenerative Medicine 33, Springer Science Business Media, New York, USA.
- Ge W, Jiang J, Baroja ML, Arp J, Zassoko R, et al. (2009) Infusion of mesenchymal stem cells and rapamycin synergize to attenuate alloimmune responses and promote cardiac allograft tolerance. Am J Transplant 9: 1760-1772.
- Crop, MJ, Baan CC, Korevaar SS, Ijzermans JN, Alwayn IP, et al. (2009) Donor-derived mesenchymal stem cells suppress alloreactivity of kidney transplant patients. Transplantation 87: 896-906.
- Silverstein DM (2009) Inflammation after renal transplantation: Role in the development of graft dysfunction and potential therapies. Journal and Organ Dysfunction 5: 233-241.
- Tan J, Wu W, Xu X, Liao L, Zheng F, et al. (2012) Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: a randomized controlled trial. JAMA 307: 1169-1177.
- Hanidziar D, Koulmanda M, Strom TB (2010) Creating transplant tolerance by taming adverse intragraft innate immunity. F1000 Biol Rep 2: 83.
- Ohnishi S, Sumiyoshi H, Kitamura S, Nagaya N (2007) Mesenchymal stem cells attenuate cardiac fibroblast proliferation and collagen synthesis through paracrine actions. FEBS Lett 581: 3961-3966.
- Ninichuk V, Gross O, Segerer S, Hoffmann R, Radomska E, et al. (2006) Multipotent mesenchymal stem cells reduce interstitial fibrosis but do not delay progression of chronic kidney disease in collagen4A3-deficient mice. Kidney Int 70: 121-129.
- Ortiz LA, Gambelli F, McBride C, McBride C, Gaupp D, et al. (2003) Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci U S A 100: 8407-8411.
- Rojas M, Xu J, Woods CR, Mora AL, Spears W, et al. (2005) Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol 33: 145-152.
- Yilmaz S, Inandiklioglu N, Yildizdas D, Subasi C, Acikalin A, et al. (2013) Mesenchymal stem cell: does it work in an experimental model with acute respiratory distress syndrome? Stem Cell Rev 9: 80-92.
- Reinders ME, Rabelink TJ, de Fijter JW (2013) The role of mesenchymal stromal cells in chronic transplant rejection after solid organ transplantation. Curr Opin Organ Transplant 18: 44-50.
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