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

Inclusion Criteria:

• Age between 20-70 years
• Clinically diagnosed for hepatic cirrhosis having a Child Pugh score of B or MELD >10 but below 20
• Not willing for immediate liver transplantation either due to lack of donor tissue or financial issues
• Platelet count of > 80,000 and INR <1.6
• Life expectancy of at least 3 months based on MELD score and Child Pugh Score
• Ability to give informed consent

Exclusion Criteria:

• Age less than 20 or more than 70 years
• Have liver tumors or history of any other cancer
• Pregnant or lactating women
• Patients with hepato-renal syndrome and acute kidney injury (Any creatinine > 1.6 will be excluded)
• Evidence of ongoing sepsis - as per Surviving sepsis guideline
• Recent gastrointestinal bleeding or spontaneous bacterial peritonitis (within last one month)
• Any HIV positive patients
• Co-morbid conditions such as severe cardiac and/or pulmonary disease
• Inability to give informed consent