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stem cells: A novel approach to inhibiting acute pancreatitis
Medical Hypotheses 80 (2013) 598–600
Contents lists available at SciVerse ScienceDirect
Medical Hypotheses journal homepage: www.elsevier.com/locate/mehy
Human adipose-derived stromal/stem cells: A novel approach to inhibiting acute pancreatitis Zhang Wen, Quan Liao ⇑, Ya Hu, Shanglong Liu, Lei You, Yupei Zhao ⇑ Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tsinghua University, Beijing 100730, China
a r t i c l e
i n f o
Article history: Received 9 October 2012 Accepted 27 January 2013
a b s t r a c t Acute pancreatitis, a common necroinflammatory disease of the pancreas, remains an unsolved problem that is associated with significant morbidity and mortality. Intra-acinar cell activation of digestion enzymes triggers the events of acute pancreatitis and stimulates the production of inflammatory cytokines. Finally, inflammatory cytokines trigger inflammatory cascades that lead to systemic inflammatory response syndrome, multi-organ failure, or death. Therefore, proposing a novel strategy for acute pancreatitis would be greatly valuable. Research on adult stem cells has achieved a great deal of progress related to the repair and regeneration of tissues and organs. Human adipose-derived stromal/stem cells become a crucial model to study diseases and develop novel therapeutic applications, as these cells are plentiful, easier to obtain, and require less-invasive procedures. Accumulated data suggest human adipose-derived stromal/stem cells would be a valuable tool for cell-based therapy for inflammatory disease, autoimmune disease, tissue repair, and ischemic insults by controlling cell death, immune response, inflammation, and tissue regeneration. Thus, it is reasonable to hypothesize that human adipose-derived stromal/stem cells would be a novel approach to inhibiting inflammation and reducing acute pancreatitis. Ó 2013 Elsevier Ltd. All rights reserved.
Introduction Acute pancreatitis (AP) has high morbidity and mortality; repetitive AP would cause chronic pancreatitis and even pancreatic ductal adenocarcinoma. Overall, appropriately 20% of patients with AP have a severe course, and 10–30% of those with severe AP die [1]. Despite improvements in medical and surgical treatment in recent years, the morbidity and mortality of AP evidently have not declined. Over the past decades, our understanding of the pathogenesis of AP has significantly improved. It is now widely accepted that AP is triggered by premature activation of proenzymes within pancreatic acinar cells, thereby leading to autodigestion of the pancreas. These inflammatory reactions would stimulate the production of inflammatory cytokines, like interleukin (IL)-4, IL-5, IL-6, IL-10, tumour necrosis factor-a (TNF-a), and interferon gamma (IFN-c) from inflammatory cells. Inflammatory cascades are then triggered leading to systematic inflammatory response syndrome, multi-organ failure, or death [2,3]. To date, no definitive treatment options for AP are available. Therefore, novel therapeutic approaches are urgently needed to reduce the morbidity and mortality of AP. ⇑ Corresponding authors. Address: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tsinghua University, 1 Shuai Fu Yuan Hu Tong, Beijing 100730, China. Tel.: +86 1065196007. E-mail addresses: [email protected] (Q. Liao), [email protected] (Y. Zhao). 0306-9877/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.mehy.2013.01.034
Stem cell-based therapies for the repair and regeneration of tissues and organs offer promising therapeutic solutions for various diseases. The clinical application of either induced pluripotent stem cells or embryonic stem cells remains limited because of ethical controversies, cell regulation, and complex genetic manipulation [4,5]. Human adipose-derived stromal/stem cells (hADSCs), obtained from subcutaneous fat tissue, appear to be an ideal subpopulation of stem cells for clinical regenerative medicine. hADSCs are plentiful and originate from autologous tissues, and thus are non-immunogenic. These cells are easier to obtain, using less-invasive procedures than isolating mesenchymal stem cells (MSC) from the bone marrow [6]. A particularly interesting feature of hADSCs has recently come to light. These cells have the ability to interact with specialized cells of both the innate and adaptive immune systems, leading to immune regulation. After in vivo administration, hADSCs induce peripheral tolerance and migrate to injury tissue, where they inhibit the release of pro-inflammatory cytokines, promote the survival of damaged cells, and, finally, inhibit inflammation [7]. Hypothesis and evaluation of the hypothesis It is reasonable to hypothesize that the use of human adiposederived stromal/stem cells represents a novel approach to inhibiting inflammation and reducing acute pancreatitis. Here we outline the evidence to support the idea.
Z. Wen et al. / Medical Hypotheses 80 (2013) 598–600
599
The homing capacity of hADSCs to sites of injuries and inflammatory Baek et al. have shown that the migration of hADSCs is mediated by various growth factors and/or chemokines capable of stimulating their movement into injured/inflamed sites in vivo, thereby highlighting their therapeutic potential [8]. Platelet-derived growth factor (PDGF)-AB and transforming growth factor-b (TGFb1) were the most potent factors for mediating the migration of hADSCs. hADSCs pre-stimulated with TNF-a showed the highest ability of migration. Meanwhile, hADSCs express the various chemokine receptors: C-C chemokine receptor type 1 (CCR1), CCR7, C-X-C chemokine receptor type 5 (CXCR5), CXCR6, epidermal growth factor receptor, TGF receptor 2, and PDGF receptor-AB [8]. These chemokines anticipate the process of injury/inflammation. A functional epidermal growth factor receptor was also found to be expressed in hADSCs associated with cell migration to the site of renal injury [9]. This homing capacity guarantees that hADSCs can move into inflamed/injured areas of the pancreas. hADSCs regulate immune cells and inflammatory cytokines Recently, Choi et al. have shown that hADSCs down-regulate Thelper 1(Th1) cytokines in experimental autoimmune thyroiditis. Lymphocyte infiltration in the thyroid gland was dramatically decreased by hADSCs. Cytokine analysis revealed that hADSCs downregulate pro-inflammatory cytokines and improve the Th1/Th2 balance by down-regulating Th1 cytokines [10]. Moreover, hADSCs can suppress the proliferation of T cells and cytokine production in response to alloantigens and non-specific antigens, and could inhibit the function of B, natural killer, and dendritic cells [11–14]. In an animal model, the intravenous administration of mouse adipose-derived stem cells (ADSCs) before disease onset significantly relieved the severity of experimental autoimmune encephalomyelitis (EAE) by decreasing inflammation of the spinal cord and demyelination, and by inducing Th2-type cytokine shifts in T cells [15]. Interestingly, ADSC subtypes express activated a4 integrins and adhere to the areas associated with inflamed brain venules, resulting in an accumulation of ADSCs in the inflamed central nervous system (CNS). Accumulating data suggest that ADSCs represent a promising therapeutic strategy for chronic inflammatory diseases of the CNS [15]. Furthermore, the application of ADSCs has great potential in therapeutic intervention related to autoimmune-associated tissue damage, such as atopic dermatitis, rheumatoid arthritis, polymyotitis, and multiple sclerosis [16]. hADSCs improve tissue repair and regeneration Local or systemic administration of hADSCs has been reported to improve tissue repair and regeneration after hypoxia–ischemia-induced brain damage [17], myocardial infarction [18], liver injury [19], and allergic rhinitis [20]. In a rat model, the administration of secreted factors by ASCs protects neurons from brain hypoxic-ischemic injury and improves repair function. Some neurotrophic factors secreted by ASCs have been identified, such as insulin-like growth factor-1 and brain-derived neutrotrophic factor, which are thought to contribute to the protective effects of ASCs [17]. Cai et al. have shown that local injections of hADSCs induce angiogenesis and nerve sprouting following myocardial infarction in athymic rats. hADSCs were persistent at 1 month in the peri-infarct region, despite the fact that they did not exhibit significant cardiomyocyte differentiation [18]. In a mouse model associated with CCl4-caused liver injury, Banas et al. observed that hADSCs secrete IL-1Ra, IL-8, granulocyte–macrophage colonystimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), monocyte chemotactic protein 1, hepatocyte growth factors, and nerve growth factor, and can improve liver repair and
Fig. 1. Schematic illustration of the potential therapeutic effects of human adiposederived stem cells (hADSCs) on acute pancreatitis (AP). Various etiologies cause damages to pancreatic acinar cell, resulting in the activation of proenzymes, autodigestion, and acute inflammation of the pancreas. The imbalance between anti-inflammatory and pro-inflammatory cytokines results in systemic inflammatory response syndrome (SIRS), multiple organ failure (MOF). The hypothesis that hADSCs inhibit inflammation and reduce AP, is most likely due to inhibiting T helper cell, (Th1 and Th2) B, Nature killer cell (NK cell), and dendritic cell (DC), stimulating the production of anti-inflammatory cytokines and improving tissue repair.
accelerate liver regeneration [19]. Thus, these findings suggest that hADSCs may account for their therapeutic efficacy in animal models of liver diseases and may be a promising strategy for liver disease treatment. It has been found that mouse ADSCs can migrate to the nasal mucosa in the allergic rhinitis mouse model and inhibit eosinophilic inflammation, partly via shifting to Th1 from a Th2 immune response to allergens [20]. However, it should be noted that the suppression of cellular immunomodulatory properties is a double-edged sword, as it could weaken immune responses against cancer. It must therefore be carefully investigated whether or not hADSCs can promote malignant transformation and/or tumourigenesis. Accordingly we propose that human adipose-derived stromal/ stem cells would be a potential therapeutic strategy for inhibiting inflammation and reducing acute pancreatitis, based on its properties that control inflammation, immune response, and tissue repair (Fig. 1). Further research should focus on the interaction between hADSCs and pancreatic acinar cells, immune cells, pancreatic stellate cells, and fibroblasts. In so doing, hADSCs would be available in preclinical trials to translate this strategy into clinical practice. Conclusion It could be concluded that human adipose-derived stromal/ stem cells may be a promising approach to inhibiting inflammation and reducing acute pancreatitis. Conflict of interest statement We declared no financial or any conflict related to this article. References [1] Talukdar R, Vege SS. Recent developments in acute pancreatitis. Clin Gastroenterol Hepatol 2009;7(11 Suppl):S3–9. [2] Pandol SJ, Saluja AK, Imrie CW, Banks PA. Acute pancreatitis: bench to the bedside. Gastroenterology 2007;132(3):1127–51. [3] Hegyi P, Pandol S, Venglovecz V, Rakonczay Jr Z. The acinar-ductal tango in the pathogenesis of acute pancreatitis. Gut 2011;60(4):544–52. [4] Mizuno H, Tobita M, Uysal AC. Concise review: adipose-derived stem cells as a novel tool for future regenerative medicine. Stem Cells 2012;30(5):804–10.
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Z. Wen et al. / Medical Hypotheses 80 (2013) 598–600
[5] Ansboro S, Greiser U, Barry F, Murphy M. Strategies for improved targeting of therapeutic cells: implications for tissue repair. Eur Cells Mater 2012;23:310–9. [6] Mizuno H. Adipose-derived stem and stromal cells for cell-based therapy: current status of preclinical studies and clinical trials. Curr Opin Mol Ther 2010;12(4):442–9. [7] Tran TT, Kahn CR. Transplantation of adipose tissue and stem cells: role in metabolism and disease. Nat Rev Endocrinol 2010;6(4):195–213. [8] Baek SJ, Kang SK, Ra JC. In vitro migration capacity of human adipose tissue-derived mesenchymal stem cells reflects their expression of receptors for chemokines and growth factors. Exp Mol Med 2011;43(10):596–603. [9] Baer PC, Schubert R, Bereiter-Hahn J, Plosser M, Geiger H. Expression of a functional epidermal growth factor receptor on human adipose-derived mesenchymal stem cells and its signaling mechanism. Eur J Cell Biol 2009;88(5):273–83. [10] Choi EW, Shin IS, Lee HW, Park SY, Park JH, Nam MH, et al. Transplantation of CTLA4Ig gene-transduced adipose tissue-derived mesenchymal stem cells reduces inflammatory immune response and improves Th1/Th2 balance in experimental autoimmune thyroiditis. J Gene Med 2011;13(1):3–16. [11] Corcione A, Benvenuto F, Ferretti E, Giunti D, Cappiello V, Cazzanti F, et al. Human mesenchymal stem cells modulate B-cell functions. Blood 2006;107(1):367–72. [12] Spaggiari GM, Capobianco A, Abdelrazik H, Becchetti F, Mingari MC, Moretta L. Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2. Blood 2008;111(3):1327–33.
[13] Zhou Y, Yuan J, Zhou B, Lee AJ, Ghawji Jr M, Yoo TJ. The therapeutic efficacy of human adipose tissue-derived mesenchymal stem cells on experimental autoimmune hearing loss in mice. Immunology 2011;133(1):133–40. [14] Jiang XX, Zhang Y, Liu B, Zhang SX, Wu Y, Yu XD, et al. Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood 2005;105(10):4120–6. [15] Constantin G, Marconi S, Rossi B, Angiari S, Calderan L, Anghileri E, et al. Adipose-derived mesenchymal stem cells ameliorate chronic experimental autoimmune encephalomyelitis. Stem Cells 2009;27(10):2624–35. [16] Ra JC, Kang SK, Shin IS, Park HG, Joo SA, Kim JG, et al. Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-expanded autologous adipose tissue derived mesenchymal stem cells. J Trans Med 2011;9:181. [17] Wei X, Du Z, Zhao L, Feng D, Wei G, He Y, et al. IFATS collection: the conditioned media of adipose stromal cells protect against hypoxia-ischemiainduced brain damage in neonatal rats. Stem Cells 2009;27(2):478–88. [18] Cai L, Johnstone BH, Cook TG, Tan J, Fishbein MC, Chen PS, et al. IFATS collection: human adipose tissue-derived stem cells induce angiogenesis and nerve sprouting following myocardial infarction, in conjunction with potent preservation of cardiac function. Stem Cells 2009;27(1):230–7. [19] Banas A, Teratani T, Yamamoto Y, Tokuhara M, Takeshita F, Osaki M, et al. IFATS collection: in vivo therapeutic potential of human adipose tissue mesenchymal stem cells after transplantation into mice with liver injury. Stem Cells 2008;26(10):2705–12. [20] Cho KS, Park HK, Park HY, Jung JS, Jeon SG, Kim YK, et al. IFATS collection: immunomodulatory effects of adipose tissue-derived stem cells in an allergic rhinitis mouse model. Stem Cells 2009;27(1):259–65.
Contents lists available at SciVerse ScienceDirect
Medical Hypotheses journal homepage: www.elsevier.com/locate/mehy
Human adipose-derived stromal/stem cells: A novel approach to inhibiting acute pancreatitis Zhang Wen, Quan Liao ⇑, Ya Hu, Shanglong Liu, Lei You, Yupei Zhao ⇑ Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tsinghua University, Beijing 100730, China
a r t i c l e
i n f o
Article history: Received 9 October 2012 Accepted 27 January 2013
a b s t r a c t Acute pancreatitis, a common necroinflammatory disease of the pancreas, remains an unsolved problem that is associated with significant morbidity and mortality. Intra-acinar cell activation of digestion enzymes triggers the events of acute pancreatitis and stimulates the production of inflammatory cytokines. Finally, inflammatory cytokines trigger inflammatory cascades that lead to systemic inflammatory response syndrome, multi-organ failure, or death. Therefore, proposing a novel strategy for acute pancreatitis would be greatly valuable. Research on adult stem cells has achieved a great deal of progress related to the repair and regeneration of tissues and organs. Human adipose-derived stromal/stem cells become a crucial model to study diseases and develop novel therapeutic applications, as these cells are plentiful, easier to obtain, and require less-invasive procedures. Accumulated data suggest human adipose-derived stromal/stem cells would be a valuable tool for cell-based therapy for inflammatory disease, autoimmune disease, tissue repair, and ischemic insults by controlling cell death, immune response, inflammation, and tissue regeneration. Thus, it is reasonable to hypothesize that human adipose-derived stromal/stem cells would be a novel approach to inhibiting inflammation and reducing acute pancreatitis. Ó 2013 Elsevier Ltd. All rights reserved.
Introduction Acute pancreatitis (AP) has high morbidity and mortality; repetitive AP would cause chronic pancreatitis and even pancreatic ductal adenocarcinoma. Overall, appropriately 20% of patients with AP have a severe course, and 10–30% of those with severe AP die [1]. Despite improvements in medical and surgical treatment in recent years, the morbidity and mortality of AP evidently have not declined. Over the past decades, our understanding of the pathogenesis of AP has significantly improved. It is now widely accepted that AP is triggered by premature activation of proenzymes within pancreatic acinar cells, thereby leading to autodigestion of the pancreas. These inflammatory reactions would stimulate the production of inflammatory cytokines, like interleukin (IL)-4, IL-5, IL-6, IL-10, tumour necrosis factor-a (TNF-a), and interferon gamma (IFN-c) from inflammatory cells. Inflammatory cascades are then triggered leading to systematic inflammatory response syndrome, multi-organ failure, or death [2,3]. To date, no definitive treatment options for AP are available. Therefore, novel therapeutic approaches are urgently needed to reduce the morbidity and mortality of AP. ⇑ Corresponding authors. Address: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tsinghua University, 1 Shuai Fu Yuan Hu Tong, Beijing 100730, China. Tel.: +86 1065196007. E-mail addresses: [email protected] (Q. Liao), [email protected] (Y. Zhao). 0306-9877/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.mehy.2013.01.034
Stem cell-based therapies for the repair and regeneration of tissues and organs offer promising therapeutic solutions for various diseases. The clinical application of either induced pluripotent stem cells or embryonic stem cells remains limited because of ethical controversies, cell regulation, and complex genetic manipulation [4,5]. Human adipose-derived stromal/stem cells (hADSCs), obtained from subcutaneous fat tissue, appear to be an ideal subpopulation of stem cells for clinical regenerative medicine. hADSCs are plentiful and originate from autologous tissues, and thus are non-immunogenic. These cells are easier to obtain, using less-invasive procedures than isolating mesenchymal stem cells (MSC) from the bone marrow [6]. A particularly interesting feature of hADSCs has recently come to light. These cells have the ability to interact with specialized cells of both the innate and adaptive immune systems, leading to immune regulation. After in vivo administration, hADSCs induce peripheral tolerance and migrate to injury tissue, where they inhibit the release of pro-inflammatory cytokines, promote the survival of damaged cells, and, finally, inhibit inflammation [7]. Hypothesis and evaluation of the hypothesis It is reasonable to hypothesize that the use of human adiposederived stromal/stem cells represents a novel approach to inhibiting inflammation and reducing acute pancreatitis. Here we outline the evidence to support the idea.
Z. Wen et al. / Medical Hypotheses 80 (2013) 598–600
599
The homing capacity of hADSCs to sites of injuries and inflammatory Baek et al. have shown that the migration of hADSCs is mediated by various growth factors and/or chemokines capable of stimulating their movement into injured/inflamed sites in vivo, thereby highlighting their therapeutic potential [8]. Platelet-derived growth factor (PDGF)-AB and transforming growth factor-b (TGFb1) were the most potent factors for mediating the migration of hADSCs. hADSCs pre-stimulated with TNF-a showed the highest ability of migration. Meanwhile, hADSCs express the various chemokine receptors: C-C chemokine receptor type 1 (CCR1), CCR7, C-X-C chemokine receptor type 5 (CXCR5), CXCR6, epidermal growth factor receptor, TGF receptor 2, and PDGF receptor-AB [8]. These chemokines anticipate the process of injury/inflammation. A functional epidermal growth factor receptor was also found to be expressed in hADSCs associated with cell migration to the site of renal injury [9]. This homing capacity guarantees that hADSCs can move into inflamed/injured areas of the pancreas. hADSCs regulate immune cells and inflammatory cytokines Recently, Choi et al. have shown that hADSCs down-regulate Thelper 1(Th1) cytokines in experimental autoimmune thyroiditis. Lymphocyte infiltration in the thyroid gland was dramatically decreased by hADSCs. Cytokine analysis revealed that hADSCs downregulate pro-inflammatory cytokines and improve the Th1/Th2 balance by down-regulating Th1 cytokines [10]. Moreover, hADSCs can suppress the proliferation of T cells and cytokine production in response to alloantigens and non-specific antigens, and could inhibit the function of B, natural killer, and dendritic cells [11–14]. In an animal model, the intravenous administration of mouse adipose-derived stem cells (ADSCs) before disease onset significantly relieved the severity of experimental autoimmune encephalomyelitis (EAE) by decreasing inflammation of the spinal cord and demyelination, and by inducing Th2-type cytokine shifts in T cells [15]. Interestingly, ADSC subtypes express activated a4 integrins and adhere to the areas associated with inflamed brain venules, resulting in an accumulation of ADSCs in the inflamed central nervous system (CNS). Accumulating data suggest that ADSCs represent a promising therapeutic strategy for chronic inflammatory diseases of the CNS [15]. Furthermore, the application of ADSCs has great potential in therapeutic intervention related to autoimmune-associated tissue damage, such as atopic dermatitis, rheumatoid arthritis, polymyotitis, and multiple sclerosis [16]. hADSCs improve tissue repair and regeneration Local or systemic administration of hADSCs has been reported to improve tissue repair and regeneration after hypoxia–ischemia-induced brain damage [17], myocardial infarction [18], liver injury [19], and allergic rhinitis [20]. In a rat model, the administration of secreted factors by ASCs protects neurons from brain hypoxic-ischemic injury and improves repair function. Some neurotrophic factors secreted by ASCs have been identified, such as insulin-like growth factor-1 and brain-derived neutrotrophic factor, which are thought to contribute to the protective effects of ASCs [17]. Cai et al. have shown that local injections of hADSCs induce angiogenesis and nerve sprouting following myocardial infarction in athymic rats. hADSCs were persistent at 1 month in the peri-infarct region, despite the fact that they did not exhibit significant cardiomyocyte differentiation [18]. In a mouse model associated with CCl4-caused liver injury, Banas et al. observed that hADSCs secrete IL-1Ra, IL-8, granulocyte–macrophage colonystimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), monocyte chemotactic protein 1, hepatocyte growth factors, and nerve growth factor, and can improve liver repair and
Fig. 1. Schematic illustration of the potential therapeutic effects of human adiposederived stem cells (hADSCs) on acute pancreatitis (AP). Various etiologies cause damages to pancreatic acinar cell, resulting in the activation of proenzymes, autodigestion, and acute inflammation of the pancreas. The imbalance between anti-inflammatory and pro-inflammatory cytokines results in systemic inflammatory response syndrome (SIRS), multiple organ failure (MOF). The hypothesis that hADSCs inhibit inflammation and reduce AP, is most likely due to inhibiting T helper cell, (Th1 and Th2) B, Nature killer cell (NK cell), and dendritic cell (DC), stimulating the production of anti-inflammatory cytokines and improving tissue repair.
accelerate liver regeneration [19]. Thus, these findings suggest that hADSCs may account for their therapeutic efficacy in animal models of liver diseases and may be a promising strategy for liver disease treatment. It has been found that mouse ADSCs can migrate to the nasal mucosa in the allergic rhinitis mouse model and inhibit eosinophilic inflammation, partly via shifting to Th1 from a Th2 immune response to allergens [20]. However, it should be noted that the suppression of cellular immunomodulatory properties is a double-edged sword, as it could weaken immune responses against cancer. It must therefore be carefully investigated whether or not hADSCs can promote malignant transformation and/or tumourigenesis. Accordingly we propose that human adipose-derived stromal/ stem cells would be a potential therapeutic strategy for inhibiting inflammation and reducing acute pancreatitis, based on its properties that control inflammation, immune response, and tissue repair (Fig. 1). Further research should focus on the interaction between hADSCs and pancreatic acinar cells, immune cells, pancreatic stellate cells, and fibroblasts. In so doing, hADSCs would be available in preclinical trials to translate this strategy into clinical practice. Conclusion It could be concluded that human adipose-derived stromal/ stem cells may be a promising approach to inhibiting inflammation and reducing acute pancreatitis. Conflict of interest statement We declared no financial or any conflict related to this article. References [1] Talukdar R, Vege SS. Recent developments in acute pancreatitis. Clin Gastroenterol Hepatol 2009;7(11 Suppl):S3–9. [2] Pandol SJ, Saluja AK, Imrie CW, Banks PA. Acute pancreatitis: bench to the bedside. Gastroenterology 2007;132(3):1127–51. [3] Hegyi P, Pandol S, Venglovecz V, Rakonczay Jr Z. The acinar-ductal tango in the pathogenesis of acute pancreatitis. Gut 2011;60(4):544–52. [4] Mizuno H, Tobita M, Uysal AC. Concise review: adipose-derived stem cells as a novel tool for future regenerative medicine. Stem Cells 2012;30(5):804–10.
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Z. Wen et al. / Medical Hypotheses 80 (2013) 598–600
[5] Ansboro S, Greiser U, Barry F, Murphy M. Strategies for improved targeting of therapeutic cells: implications for tissue repair. Eur Cells Mater 2012;23:310–9. [6] Mizuno H. Adipose-derived stem and stromal cells for cell-based therapy: current status of preclinical studies and clinical trials. Curr Opin Mol Ther 2010;12(4):442–9. [7] Tran TT, Kahn CR. Transplantation of adipose tissue and stem cells: role in metabolism and disease. Nat Rev Endocrinol 2010;6(4):195–213. [8] Baek SJ, Kang SK, Ra JC. In vitro migration capacity of human adipose tissue-derived mesenchymal stem cells reflects their expression of receptors for chemokines and growth factors. Exp Mol Med 2011;43(10):596–603. [9] Baer PC, Schubert R, Bereiter-Hahn J, Plosser M, Geiger H. Expression of a functional epidermal growth factor receptor on human adipose-derived mesenchymal stem cells and its signaling mechanism. Eur J Cell Biol 2009;88(5):273–83. [10] Choi EW, Shin IS, Lee HW, Park SY, Park JH, Nam MH, et al. Transplantation of CTLA4Ig gene-transduced adipose tissue-derived mesenchymal stem cells reduces inflammatory immune response and improves Th1/Th2 balance in experimental autoimmune thyroiditis. J Gene Med 2011;13(1):3–16. [11] Corcione A, Benvenuto F, Ferretti E, Giunti D, Cappiello V, Cazzanti F, et al. Human mesenchymal stem cells modulate B-cell functions. Blood 2006;107(1):367–72. [12] Spaggiari GM, Capobianco A, Abdelrazik H, Becchetti F, Mingari MC, Moretta L. Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2. Blood 2008;111(3):1327–33.
[13] Zhou Y, Yuan J, Zhou B, Lee AJ, Ghawji Jr M, Yoo TJ. The therapeutic efficacy of human adipose tissue-derived mesenchymal stem cells on experimental autoimmune hearing loss in mice. Immunology 2011;133(1):133–40. [14] Jiang XX, Zhang Y, Liu B, Zhang SX, Wu Y, Yu XD, et al. Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood 2005;105(10):4120–6. [15] Constantin G, Marconi S, Rossi B, Angiari S, Calderan L, Anghileri E, et al. Adipose-derived mesenchymal stem cells ameliorate chronic experimental autoimmune encephalomyelitis. Stem Cells 2009;27(10):2624–35. [16] Ra JC, Kang SK, Shin IS, Park HG, Joo SA, Kim JG, et al. Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-expanded autologous adipose tissue derived mesenchymal stem cells. J Trans Med 2011;9:181. [17] Wei X, Du Z, Zhao L, Feng D, Wei G, He Y, et al. IFATS collection: the conditioned media of adipose stromal cells protect against hypoxia-ischemiainduced brain damage in neonatal rats. Stem Cells 2009;27(2):478–88. [18] Cai L, Johnstone BH, Cook TG, Tan J, Fishbein MC, Chen PS, et al. IFATS collection: human adipose tissue-derived stem cells induce angiogenesis and nerve sprouting following myocardial infarction, in conjunction with potent preservation of cardiac function. Stem Cells 2009;27(1):230–7. [19] Banas A, Teratani T, Yamamoto Y, Tokuhara M, Takeshita F, Osaki M, et al. IFATS collection: in vivo therapeutic potential of human adipose tissue mesenchymal stem cells after transplantation into mice with liver injury. Stem Cells 2008;26(10):2705–12. [20] Cho KS, Park HK, Park HY, Jung JS, Jeon SG, Kim YK, et al. IFATS collection: immunomodulatory effects of adipose tissue-derived stem cells in an allergic rhinitis mouse model. Stem Cells 2009;27(1):259–65.