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Endocrine, Metabolic & Immune Disorders - Drug Targets

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ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

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Research Article

The Effect of Stem Cell Transplantation Therapy for Post Viral Chronic Liver Cell Failure on Associated Type II Diabetes Mellitus: A Pilot Study

Author(s): Tamer Haydara, Mostafa Gabr, Mohamed Abofreikha, Abeer Bahnasy, Hosny Salama, Mohammed Elhendawy, Mahmoud Elkadeem and Sherief Abd-Elsalam*

Volume 20, Issue 6, 2020

Page: [903 - 916] Pages: 14

DOI: 10.2174/1871530319666191202125402

Price: $65

Abstract

Background: It was observed that type II diabetes mellitus associated with chronic liver failure improved after stem cell transplantation. However, there were no adequate studies regarding this issue. The aim of this study was to evaluate the effect of stem cell transplantation on associated type II diabetes mellitus and on the liver function tests.

Methods: This pilot study included 30 patients of post-hepatitis chronic liver failure who were classified into two groups: Group I included patients with chronic liver cell failure associated with type 2 diabetes. Group II included patients without type II diabetes. Autologous CD34+ and CD133+ stem cells were percutaneously infused into the portal vein. Responders (regarding the improvement of diabetes as well as improvement of liver condition) and non-responders were determined. Patients were followed up for one, three and six months after the intervention evaluating their three-hour glucose tolerance test, C- peptide (Fasting and postprandial), Child-Pugh score and performance score one month, three months, and six months after stem cell therapy.

Results: Both synthetic and excretory functions of the liver were improved in 10 patients (66.66 %) of group I and in 12 patients (80 %) of group II. Significant improvement in the Oral Glucose Tolerance Test in the responders of both the groups was well defined from the 3rd month and this was comparable to changes in liver function tests and Child-Pugh score.

Conclusion: Successful stem cell therapy in chronic liver cell failure patients can improve but not cure the associating type 2 diabetes by improving insulin resistance.

Keywords: Liver failure, cirrhosis, diabetes, stem cell therapy, HCV, transplantation.

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[1]
Saleh, A.M.; Hassan, E.A.; Gomaa, A.A.; El Baz, T.M.; El-Abgeegy, M.; Seleem, M.I.; Abo-Amer, Y.E.; Elsergany, H.F.; Mahmoud, E.I.E.; Abd-Elsalam, S. Impact of pre-transplant infection management on the outcome of living-donor liver transplantation in Egypt. Infect. Drug Resist., 2019, 12, 2277-2282.
[http://dx.doi.org/10.2147/IDR.S208954] [PMID: 31413604]
[2]
Fiegel, H.C.; Kneser, U.; Kluth, D.; Rolle, U. [Hepatic tissue engineering] Handchir. Mikrochir. Plast. Chir, 2010, 42(6), 337-341.
[http://dx.doi.org/10.1055/s-0030-1252045] [PMID: 20405372]
[3]
Loria, P.; Lonardo, A.; Anania, F. Liver and diabetes. A vicious circle. Hepatol. Res., 2013, 43(1), 51-64.
[http://dx.doi.org/10.1111/j.1872-034X.2012.01031.x] [PMID: 23332087]
[4]
Orkin, S.H.; Zon, L.I. Hematopoiesis: An evolving paradigm for stem cell biology. Cell, 2008, 132(4), 631-644.
[http://dx.doi.org/10.1016/j.cell.2008.01.025] [PMID: 18295580]
[5]
Graf, T.; Enver, T. Forcing cells to change lineages. Nature, 2009, 462(7273), 587-594.
[http://dx.doi.org/10.1038/nature08533] [PMID: 19956253]
[6]
Pournasr, B.; Khaloughi, K.; Salekdeh, G.H.; Totonchi, M.; Shahbazi, E.; Baharvand, H. Concise review: alchemy of biology: generating desired cell types from abundant and accessible cells. Stem Cells, 2011, 29(12), 1933-1941.
[http://dx.doi.org/10.1002/stem.760] [PMID: 21997905]
[7]
Ferber, S.; Halkin, A.; Cohen, H.; Ber, I.; Einav, Y.; Goldberg, I.; Barshack, I.; Seijffers, R.; Kopolovic, J.; Kaiser, N.; Karasik, A. Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin-induced hyperglycemia. Nat. Med., 2000, 6(5), 568-572.
[http://dx.doi.org/10.1038/75050] [PMID: 10802714]
[8]
Shternhall-Ron, K.; Quintana, F.J.; Perl, S.; Meivar-Levy, I.; Barshack, I.; Cohen, I.R.; Ferber, S. Ectopic PDX-1 expression in liver ameliorates type 1 diabetes. J. Autoimmun., 2007, 28(2-3), 134-142.
[http://dx.doi.org/10.1016/j.jaut.2007.02.010] [PMID: 17383157]
[9]
Sapir, T.; Shternhall, K.; Meivar-Levy, I.; Blumenfeld, T.; Cohen, H.; Skutelsky, E.; Eventov-Friedman, S.; Barshack, I.; Goldberg, I.; Pri-Chen, S.; Ben-Dor, L.; Polak-Charcon, S.; Karasik, A.; Shimon, I.; Mor, E.; Ferber, S. Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells. Proc. Natl. Acad. Sci. USA, 2005, 102(22), 7964-7969.
[http://dx.doi.org/10.1073/pnas.0405277102] [PMID: 15899968]
[10]
Burke, Z.D.; Tosh, D. Therapeutic potential of transdifferentiated cells. Clin. Sci. (Lond.), 2005, 108(4), 309-321.
[http://dx.doi.org/10.1042/CS20040335] [PMID: 15766332]
[11]
Tang, D.Q.; Wang, Q.; Burkhardt, B.R.; Litherland, S.A.; Atkinson, M.A.; Yang, L.J. In vitro generation of functional insulin-producing cells from human bone marrow-derived stem cells, but long-term culture running risk of malignant transformation. Am. J. Stem Cells, 2012, 1(2), 114-127.
[PMID: 22833839]
[12]
Esrefoglu, M. Role of stem cells in repair of liver injury: experimental and clinical benefit of transferred stem cells on liver failure. World J. Gastroenterol., 2013, 19(40), 6757-6773.
[http://dx.doi.org/10.3748/wjg.v19.i40.6757] [PMID: 24187451]
[13]
Wan, Y.; Garner, J.; Wu, N.; Phillip, L.; Han, Y.; McDaniel, K.; Annable, T.; Zhou, T.; Francis, H.; Glaser, S.; Huang, Q.; Alpini, G.; Meng, F. Role of stem cells during diabetic liver injury. J. Cell. Mol. Med., 2016, 20(2), 195-203.
[http://dx.doi.org/10.1111/jcmm.12723] [PMID: 26645107]
[14]
Rubenstein, A.; Clark, J.; Melani, F. Secretion of proinsulin C-peptide by pancreatic beta cells and its circulation in blood. Nature, 1969, 224, 697-696.
[http://dx.doi.org/10.1038/224697a0]
[15]
Standards of medical care in diabetes-2014. Diabetes Care, 2014, 37(Suppl. 1), S16.
[16]
Gragnoli, G.; Signorini, A.M.; Tanganelli, I. Plasma levels of insulin, C-peptide and glucagon in liver cirrhosis. J. Endocrinol. Invest., 1981, 4(1), 1-5.
[http://dx.doi.org/10.1007/BF03349405] [PMID: 7016966]
[17]
Proietto, J.; Dudley, F.J.; Aitken, P.; Alford, F.P. Hyperinsulinaemia and insulin resistance of cirrhosis: the importance of insulin hypersecretion. Clin. Endocrinol. (Oxf.), 1984, 21(6), 657-665.
[http://dx.doi.org/10.1111/j.1365-2265.1984.tb01408.x] [PMID: 6391746]
[18]
Kruszynska, Y.T.; Munro, J.; Home, P.D.; McIntyre, N. Twenty-four hour C-peptide and insulin secretion rates and diurnal profiles of glucose, lipids and intermediary metabolites in cirrhosis. Clin. Sci. (Lond.), 1992, 83(5), 597-605.
[http://dx.doi.org/10.1042/cs0830597] [PMID: 1335398]
[19]
Narita, R.; Abe, S.; Kihara, Y.; Akiyama, T.; Tabaru, A.; Otsuki, M. Insulin resistance and insulin secretion in chronic hepatitis C virus infection. J. Hepatol., 2004, 41(1), 132-138.
[http://dx.doi.org/10.1016/j.jhep.2004.03.020] [PMID: 15246219]
[20]
Nielsen, M.F.; Caumo, A.; Aagaard, N.K.; Chandramouli, V.; Schumann, W.C.; Landau, B.R.; Schmitz, O.; Vilstrup, H. Contribution of defects in glucose uptake to carbohydrate intolerance in liver cirrhosis: assessment during physiological glucose and insulin concentrations. Am. J. Physiol. Gastrointest. Liver Physiol., 2005, 288(6), G1135-G1143.
[http://dx.doi.org/10.1152/ajpgi.00278.2004] [PMID: 15637182]
[21]
Nielsen, M.F.; Aagaard, N.K.; Grøfte, T.; Frystyk, J.; Greisen, J.; Christiansen, J.S.; Holland-Fischer, P.; Vilstrup, H. Normalisation of insulin-like growth factor-I does not improve insulin action in cirrhosis. Liver Int., 2011, 31(10), 1511-1518.
[http://dx.doi.org/10.1111/j.1478-3231.2011.02599.x] [PMID: 21967317]
[22]
Ling, Q.; Dong, F.; Geng, L.; Liu, Z.; Xie, H.; Xu, X.; Zheng, S. Impacts of TCF7L2 gene polymorphisms on the susceptibility of hepatogenous diabetes and hepatocellular carcinoma in cirrhotic patients. Gene, 2013, 522(2), 214-218.
[http://dx.doi.org/10.1016/j.gene.2013.03.089] [PMID: 23558246]
[23]
Bezborodkina, N.N.; Chestnova, A.Y.; Okovity, S.V.; Kudryavtsev, B.N. Activity of glycogen synthase and glycogen phosphorylase in normal and cirrhotic rat liver during glycogen synthesis from glucose or fructose. Exp. Toxicol. Pathol., 2014, 66(2-3), 147-154.
[http://dx.doi.org/10.1016/j.etp.2013.12.001] [PMID: 24373751]
[24]
Pelkonen, R.; Kallio, H.; Suoranta, H.; Karonen, S.L. Plasma insulin, C-peptide, and blood glucose in portal, hepatic and peripheral veins in liver cirrhosis. Effect of intravenous tolbutamide. Acta Endocrinol. (Copenh.), 1981, 97(4), 496-502.
[http://dx.doi.org/10.1530/acta.0.0970496] [PMID: 7023164]
[25]
Yoo, H.; Thuluvath, P. The effect of insulin-dependent diabetes mellitus on outcome of liver transplantation. Transplantation, 2002, 74, 1007-1012.
[http://dx.doi.org/10.1097/00007890-200210150-00019]
[26]
Abd-Elsalam, S.; Habba, E.; Elkhalawany, W.; Tawfeek, S.; Elbatea, H.; El-Kalla, F.; Soliman, H.; Soliman, S.; Yousef, M.; Kobtan, A.; El Nawasany, S.; Awny, S.; Amer, I.; Mansour, L.; Rizk, F. Correlation of platelets count with endoscopic findings in a cohort of Egyptian patients with liver cirrhosis. Medicine (Baltimore), 2016, 95(23),e3853.
[http://dx.doi.org/10.1097/MD.0000000000003853] [PMID: 27281094]
[27]
Mansour, L.; El-Kalla, F.; El-Bassat, H.; Abd-Elsalam, S.; El-Bedewy, M.; Kobtan, A.; Badawi, R.; Elhendawy, M. Randomized controlled trial of scleroligation versus band ligation alone for eradication of gastroesophageal varices. Gastrointest. Endosc., 2017, 86(2), 307-315.
[http://dx.doi.org/10.1016/j.gie.2016.12.026] [PMID: 28082116]
[28]
Abdeldyem, S.M.; Goda, T.; Khodeir, S.A.; Abou Saif, S.; Abd-Elsalam, S. Nonalcoholic fatty liver disease in patients with acute ischemic stroke is associated with more severe stroke and worse outcome. J. Clin. Lipidol., 2017, 11(4), 915-919.
[http://dx.doi.org/10.1016/j.jacl.2017.04.115] [PMID: 28579247]
[29]
Tietge, U.J.; Selberg, O.; Kreter, A.; Bahr, M.J.; Pirlich, M.; Burchert, W.; Müller, M.J.; Manns, M.P.; Böker, K.H. Alterations in glucose metabolism associated with liver cirrhosis persist in the clinically stable long-term course after liver transplantation. Liver Transpl., 2004, 10(8), 1030-1040.
[http://dx.doi.org/10.1002/lt.20147] [PMID: 15390330]
[30]
Kim, S.H.; Kim, J.M.; Lee, K.A.; Park, T.S.; Baek, H.S.; Yu, H.C.; Jin, H.Y. Effect of liver transplantation on glucose levels in patients with prediabetes or type 2 diabetes. Transplant. Proc., 2014, 46(1), 225-229.
[http://dx.doi.org/10.1016/j.transproceed.2013.05.013] [PMID: 24507056]
[31]
Pallayova, M.; Wilson, V.; John, R.; Taheri, S. Liver transplantation: A potential cure for hepatogenous diabetes? Diabetes Care, 2013, 36(7),e97.
[http://dx.doi.org/10.2337/dc13-0400] [PMID: 23801819]
[32]
Tamer, E. The effect of stem cell transplantation therapy for post viral chronic liver cell failure on associated Type II diabetes mellitus. MD degree thesis, Internal Medicine, Tanta University: 2014.

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