To the Editor:

The experimental studies and clinical trials of bone marrow (BM) cell therapy for severe liver diseases have been studied extensively, although the benefit is controversial, and the underlying mechanisms remain undefined.1 With great interest, I read the article by Thomas et al.,2 who demonstrated that BM-derived differentiated macrophage cell therapy improves structural and functional parameters of experimental chronic liver injury. Their results have identified defined single cell types from BM that have beneficial effects on liver fibrosis. Their study can be hailed as an original contribution in terms of understanding the mechanisms of BM cell therapy for liver fibrosis.

However, other previous studies on BM cell therapy for liver cirrhosis have focused on stem cells that may work by hepatic differentiation or paracrine effects.3 Which kind of cells in the BM may contribute to cellular therapy for liver cirrhosis: stem cells, macrophages, or both? Here, we would like to offer our concerns regarding this proposed therapy. First, in the report by Thomas et al., the stem cells therapy group was not set to be compared with groups treated with differentiated macrophages. Thus, the different effects of these two kinds of cells on liver injury cannot be known under the same conditions. Furthermore, animal experimental studies have indicated that BM cell-derived stem cell therapy for liver fibrosis is under debate. Nevertheless, some optimistic results can be found in recent clinical trials reports,4 although safety and efficacy should be further demonstrated. Because there are many differences between mice and humans,5 more rational and legalized clinical trials based on BM-derived stem cells or macrophages should be encouraged. In addition, BM is composed of a variety of cell types such as hematopoietic stem cells, mesenchymal stem cells, and macrophages. BM cell therapy function may depend on synergistic effects of several kinds of cells, rather than defined single cell types. Thus, experimental studies based on single and combinations of cell types also need to be performed. Moreover, both posttransplant BM-derived differentiated macrophages and stem cells are in transient cell states that may only give short-term relief for liver fibrosis. Thus, repeated cell therapy may be required to acquire definitive therapeutic effects.


  1. Top of page
  • 1
    Houlihan DD, Newsome PN. Critical review of clinical trials of bone marrow stem cells in liver disease. Gastroenterology 2008; 135: 438-450.
  • 2
    Thomas JA, Pope C, Wojtacha D, Robson AJ, Gordon-Walker TT, Hartland S, et al. Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration and function. HEPATOLOGY 2011; 53: 2003-2015.
  • 3
    Kuo TK, Hung SP, Chuang CH, Chen CT, Shih YR, Fang SC, et al. Stem cell therapy for liver disease: parameters governing the success of using bone marrow mesenchymal stem cells. Gastroenterology 2008; 134: 2111-2121.
  • 4
    Stutchfield BM, Forbes SJ, Wigmore SJ. Prospects for stem cell transplantation in the treatment of hepatic disease. Liver Transpl 2010; 16: 827-836.
  • 5
    Odom DT, Dowell RD, Jacobsen ES, Gordon W, Danford TW, MacIsaac KD, et al. Tissue-specific transcriptional regulation has diverged significantly between human and mouse. Nat Genet 2007; 39: 730-732.

Tao Liu M.D.* †, Yingjie Wang M.D.*, Chenting Wen M.D.‡, Shichang Zhang M.D.§, Chunmei Zhang M.D.†, * Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China, † Department of Internal Medicine 3, The Northern Region of No. 401 Hospital, Qingdao, Shandong, China, ‡ Dongfeng General Hospital, Hubei University of Medicine, Shiyan, Hubei, China, § State Key Laboratory of Trauma, Burns and Combined Injury, Department 4, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.