AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN SUB-TERMINAL LIVER DISEASE PATIENTS.
- Haematology Department 1, Theodor Bilharz Research Institute (TBRI), Imbaba, Giza.
- Tropical Medicine Department2, Theodor Bilharz Research Institute (TBRI), Imbaba, Giza.
- Pathology Department3 Theodor Bilharz Research Institute (TBRI), Imbaba, Giza.
- Abstract
- Keywords
- References
- Cite This Article as
- Corresponding Author
Back ground and objective: The ultimate goal of this work is to evaluate the effect of autologous hematopoietic stem cells transplantation as alternative therapeutic option in patients with sub terminal liver diseases. The work divided into 3 parts: Mobilization of CD34+ HSCs to peripheral blood, Leukapheresis, Intravenous infusion of autologous CD34+ HSCs to the patient. Patients and Method: 30 patients with HCV induced liver cirrhosis divided into 3 groups: Group I: consists of 10 patients with liver cirrhosis selected as Child C with scoring range from (14-21) this group was injected with G-CSF for 5 consecutive days to mobilize stem cells from the bone marrow to peripheral blood. Group II: consists of 10 patients with liver cirrhosis selected as Child C with scoring range from (16-23). This group was injected with granulocytes colony stimulating factor (G-CSF) 5 days before collection followed by leukapheresis and peripheral vein infusion of autologous hematopoietic stem cells CD34+ on day 6. Group III: control group consists of 10 cirrhotic patients maintained on supportive medical therapy. Results: The synthetic functions of liver in both groups I and II improved as evidenced by liver function tests (serum albumin, PT / INR& serum bilirubin) and MELD score after the procedure. Conclusion: Stem cell therapy is expected to be a last chance for patients suffering from end stage liver disease ESLD and waiting for donor livers. Consequently, decrease the need for orthotropic liver transplantation especially in the early stages of liver disease.
- Sharma M, Rao P, Sasikala M, Kuncharam M, Reddy C, ?Gokak V, ?Raju B, Singh J, ?Nag P and ?Reddy D.2015; Autologous mobilized peripheral blood CD34+ cell infusion in non-viral decompensated liver cirrhosis. World J Gastroenterol 2015; (23):7264-7271.
- Margini C, Vukotic R, Brodosi L, Bernardi M and Andreone P (2014). Bone marrow derived stem cells for the treatment of end-stage liver disease; World J Gastroenterol.??(27): 9098-9105
- Zhang Z, Lin H, Shi M, Xu R, Fu J, Lv J, Chen L, Lv S, Li Y and Yu S (2012). Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients. J Gastroenterol Hepatol. ; 27Suppl 2:112?120.
- Grove J, Bruscia E and Krause D (2004)Plasticity of bone marrow-derived stem cells. Stem Cells 22:487?500.
- Mizunaga Y,?Terai S, Yamamoto N, Uchida K, Yamasaki T, Nishina H, Fujita Y, Shinoda K, Hamamoto Y andSakaida I (2012)Granulocyte colony-stimulating factor and interleukin-1β are important cytokines in repair of the cirrhotic liver after bone marrow cell infusion: comparison of humans and model mice. Cell Transplant.? 21:2363-2375.
- Jin S,?Meng X, Sun X, Han M, Liu B, Wang X, Sun L, Huang Q, Zhao R and Ban X (2010) Granulocyte colony-stimulating factor enhances bone marrow mononuclear cell homing to the liver in a mouse model of acute hepatic injury. Dig Dis Sci.? 55:2805-2813.
- Al Tayeb H, El Dorry A, Amer N, Mowafy N, Zimaity M, Bayoumy E and Saleh S (2015). Autologous stem cells transplantation in Egyptian patients with liver cirrhosis on top of hepatitis C virus. Int J Stem Cells, 8: 118-132.
- Gaia S,?Smedile A, Omed? P, Olivero A, Sanavio F, Balzola F, Ottobrelli A, Abate ML, Marzano A, Rizzetto M ?(2006)Feasibility and safety of G-CSF administration to induce bone marrow-derived cells mobilization in patients with end stage liver disease. J Hepatol. 45:13-19.
- Spahr L,?Lambert JF, Rubbia-Brandt L, Chalandon Y, Frossard JL, Giostra E, Hadengue A (2008)Granulocyte-colony stimulating factor induces proliferation of hepatic progenitors in alcoholic steatohepatitis: a randomized trial. Hepatology.? 48:221-229
- Lorenzini S,?Isidori A, Catani L, Gramenzi A, Talarico S, Bonifazi F, Giudice V, Conte R, Baccarani M, Bernardi M (2008)Stem cell mobilization and collection in patients with liver cirrhosis. Aliment Pharmacol Ther.? 27:932-939.
- Picardi M,?De Rosa G, Selleri C, Scarpato N, Soscia E, Martinelli V, Ciancia R andRotoli B(2003) Spleen enlargement following recombinant human granulocyte colony-stimulating factor administration for peripheral blood stem cell mobilization. Haematologica.? 88:794-800.
- Falzetti F,?Aversa F, Minelli O and Tabilio A (1999)Spontaneous rupture of spleen during peripheral blood stem-cell mobilization in a healthy donor. Lancet.? 353:555
- Zhang Mand Huang B (2012)the multi-differentiation potential of peripheral blood mononuclear cells. Stem Cell Res., 30; 3(6):48.
- Saito T,?Tomita K, Haga H, Okumoto K, Ueno Y(2013).?Bone marrow cell-based regenerative therapy for liver cirrhosis. World J Methodol. 3:65-69.
- Palanisamy AP,?Taber DJ, Sutter AG, Nadig SN, Dowden JE, McGillicuddy JW, Baliga PK andChavin KD (2015)Clinical outcomes and costs associated with in-hospital biliary complications after liver transplantation: a cross-sectional analysis. J Gastrointest Surg.? 19:282-289.
- Nicolas C, Hickey R, Chen H, Mao S, Manuela Lopera Higuita M, Wang Y and Nyberg S (2017). Liver Regenerative Medicine: From Hepatocyte Transplantation to Bioartificial Livers and Bioengineered Grafts. Stem Cells,35: 42?50
- Shiota G and Itaba N (2017). Progress in stem cell-based therapy for liver disease Hepatology Research, 47: 127?141.
- Panminerva medica Article (2010) Literature Review 52(2):149-65???
- De Lucas, Perez LM and Galvez BG (2017)?Importance and regulation of adult stem cell migration; J cell Mol Med doi:1111/jcmm13422
- Anthony DF and Shiels PG (2013)Exploiting paracrine mechanisms of tissue regeneration to repair damaged organs, Transplantation Research; 20: 2 (1):10
- Salama H, Zekri A, Bahnassy A, Medhat E, Halim H, ?Ahmed O, Mohamed G ?Al Alim S, and Sherif G (2010)?Autologous CD34+ and CD133+ stem cells transplantation in patients with end stage liver disease: World J Gastroenterol. 16(42): 5297?5305.
- Zekri A, Salama H, Medhat E, Musa S, Abdel-Haleem H, Ahmed O, Abdel Hafez H, Lotfy M, Zachariah K and Bahnassy A (2015). The impact of repeated autologous infusion of hematopoietic stem cells in patients with liver insufficiency. Stem Cell Research & Therapy, 6:118-125.
- Salama H, Zekri A, Medhat E, Abd- Al Alim S, Ahmed O, Bahnassy A, Lotfy M, Ahmed R and Musa S (2014). Peripheral vein infusion of autologous mesenchymal stem cells in Egyptian HCV-positive patients with end-stage liver disease.Stem Cell Research & Therapy, 5:70-80.
- Levicar N, Pai M, Habib N, Tait P, Jiao L, Marley S, Davis J, Dazzi F, Samadja C, Jensen S, Nicholls J, Apperley J, and Gordon M (2008)Long term clinical results of autologous infusion of mobilized adult bone marrow derived CD34+ cells in patients with chronic liver diseases. Cell Prolif. 41 (Suppl. 1), 115-125.
- Terai S, Ishikawa T, Omori K, Aoyama K, Marumoto Y, Urata Y, Yokoyama Y, Uchida K, Yamasaki T andFujii Y (2006)?Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy. Stem Cells. 24:2292?2298.
- Gordon M, Levicar N, Pai M, Bachellier P, Dimarakis I, Al-Allaf F, M'Hamdi H, Thalji T, Welsh J and Marley S (2006)Characterization and clinical application of human CD34+ stem/progenitor cell populations mobilized into the blood by granulocyte colony-stimulating factor. Stem Cells. 24 (7) 1822-30
- Nakamura K, Nonaka H, Saito H,Tanaka M andMiyajima A(2004) Hepatocytes proliferation and tissue remodling is impaired after liver injury in oncostatin M receptor knockout mice. Hepatology, 39:635-644.
- Mohamadnejad M,?Namiri M, Bagheri M, Hashemi S, Ghanaati H, ZareMehrjardi N, KazemiAshtiani S, Malekzadeh R andBaharvand H (2007)Phase 1 human trial of autologous bone marrow-hematopoietic stem cell transplantation in patients with decompensated cirrhosis. World J Gastroenterol.? 13:3359-3363
- Garg V, Garg H, Khan A, Trehanpati N, Kumar A, Sharma B, Sakhuja PandSarin S. (2013)Granulocyte colony-stimulating factor mobilizes CD34 (+) cells and improves survival of patients with acute-on-chronic liver failure.World J Methodol. 3(4): 65?69.
- Gaia S, Smedile A, Omed? P, Olivero A, Sanavio F, Balzola F, Ottobrelli A, Abate M, Marzano A, Rizzetto MandTarella C (2006) Feasibility and safety of G-CSF administration to induce bone marrow derived cells mobilization in patients with end stage liver disease. J Hepatol; 45:13?19.
- Jin S,?Meng X, Sun X, Han M, Liu B, Wang X, Sun L, Huang Q, Zhao R and Ban X (2010)Granulocyte colony-stimulating factor enhances bone marrow mononuclear cell homing to the liver in a mouse model of acute hepatic injury. Dig Dis Sci.?55:2805-2813.
- Lorenzini S,?Isidori A, Catani L, Gramenzi A, Talarico S, Bonifazi F, Giudice V, Conte R, Baccarani M andBernardi M ?(2008)Stem cell mobilization and collection in patients with liver cirrhosis. Aliment Pharmacol Ther.? 27:932-939
- Falzetti F,?Aversa F, Minelli O andTabilio A (1999)Spontaneous rupture of spleen during peripheral blood stem-cell mobilization in a healthy donor. Lancet.? 353:555
- Sakaida I,?Terai S, Yamamoto N, Aoyama K, Ishikawa T, Nishina H andOkita K ?(2004)Transplantation of bone marrow cells reduces CCl4-induced liver fibrosis in mice. Hepatology.?40:1304-1311
- Jang Y,?Collector M, Baylin S, Diehl A andSharkis S ?(2004)Hematopoietic stem cells convert into liver cells within days without fusion. Nat CellBiol.? 6:532-539.
[Iman A. Khaled, Motaz Hassan, Maged E. Ghanam, Olfat Hammam, Omar Sabry and Marwa Wahdan. (2018); AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN SUB-TERMINAL LIVER DISEASE PATIENTS. Int. J. of Adv. Res. 6 (Mar). 756-769] (ISSN 2320-5407). www.journalijar.com
Haematology Department, Theodor Bilharz Research Institute (TBRI)