Combination of Autologous MSC and HSC Infusion in Patients With Decompensated Cirrhosis

Summary

Though the results of autologous CD34+ cell infusion and MSC in independent studies have shown promise, yet they are yet to reach the desired long term outcome. The possible postulation for this is possibly because when using autologous CD34+ cell infusion, the inflammatory milieu of the liver may not be conducive for sustained effects of the mobilized CD 34+ cells. MSC have immunomodulatory effect (ref) and may improve the liver environment making it more beneficial for the CD34+ cells to function and survive. In addition, MSC has ben shown to produce hepatocyte growth factor which is protective against liver injury and beneficial for liver regeneration (shown in above tables). However, it remains to be understood how MSCs promote liver stem stem cells to differentiate into hepatocytes or expand the residual hepatocyte population. MSC can also directly inhibit the activation of hepatic stellate cells, the main source of extracellular matrix via MSC derived IL 10 and TNF-αand may also induce hepatic stellate cell apoptosis. Current lacunae in cell based therapy is based on the poor consensus and understanding on the best type of cells to be used, the ideal number of cells, the most appropriate route of administration and the need for repeat dosing . The concept that combination of autologous hematopoietic and mesenchymal stem cells infusion may be more beneficial than infusing any one of them alone has been discussed in many scientific forums but there are no study till date to either see the safety as well as the efficacy of this proof of concept . With this above background data, we propose a study design which will be a safety study for combination use of autologous CD34+ and MSC

Timeline

Start

2019-07-01

Primary completion

2020-08-01

Completion

2020-09-01

Publications

• Background Amer ME, El-Sayed SZ, El-Kheir WA, Gabr H, Gomaa AA, El-Noomani N, Hegazy M. Clinical and laboratory evaluation of patients with end-stage liver cell failure injected with bone marrow-derived hepatocyte-like cells. Eur J Gastroenterol Hepatol. 2011 Oct;23(10):936-41. doi: 10.1097/MEG.0b013e3283488b00.
• Background Hang HL, Xia Q. Role of BMSCs in liver regeneration and metastasis after hepatectomy. World J Gastroenterol. 2014 Jan 7;20(1):126-32. doi: 10.3748/wjg.v20.i1.126.
• Background Gordon MY, Levicar N, Pai M, Bachellier P, Dimarakis I, Al-Allaf F, M'Hamdi H, Thalji T, Welsh JP, Marley SB, Davies J, Dazzi F, Marelli-Berg F, Tait P, Playford R, Jiao L, Jensen S, Nicholls JP, Ayav A, Nohandani M, Farzaneh F, Gaken J, Dodge R, Alison M, Apperley JF, Lechler R, Habib NA. Characterization and clinical application of human CD34+ stem/progenitor cell populations mobilized into the blood by granulocyte colony-stimulating factor. Stem Cells. 2006 Jul;24(7):1822-30. doi: 10.1634/stemcells.2005-0629. Epub 2006 Mar 23.
• Sharma M, Pondugala PK, Jaggaihgari S, Mitnala S, Krishna VV, Jaishetwar G, Naik P, Kumar P, Kulkarni A, Gupta R, Singh JR, Darisetty S, Sekharan A, Reddy DN, Rao GV, Syeda F, Jagtap N, Rao PN. Safety Assessment of Autologous Stem Cell Combination Therapy in Patients With Decompensated Liver Cirrhosis: A Pilot Study. J Clin Exp Hepatol. 2022 Jan-Feb;12(1):80-88. doi: 10.1016/j.jceh.2021.03.010. Epub 2021 Apr 2.

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