Evaluation of porcine mesenchymal stem cells for therapeutic use in human liver cancer

Abstract

Abstract. Mesenchymal stem cell (MSC) transplantation is suggested for therapy of end-stage liver disease, due to e.g. liver cancer and metastasis. Liver transplantation is the only therapeutic option so far but donor organs are short. Also, the availability of allogeneic human MSCs for liver regeneration is limited. Therefore, we evaluated the suitability of porcine bone marrow MSCs from semi-adult pigs and found that morphology, surface expression pattern and multilineage differentiation are similar to those of human MSCs. Porcine MSCs differentiated to a hepatocyte-like phenotype and expressed porcine mRNA of typical liver proteins. However, hepatocyte-like MSCs failed to express the corresponding proteins and did not produce glycogen and urea as primary porcine hepatocytes do. Porcine MSCs were immunotolerated, since they did not activate resting human PBMCs, and were not attacked by human activated PBMCs. However, porcine MSCs led to enhanced proliferation of human pre-activated PBMCs suggesting that immunotoleration of porcine MSCs in the human system has limitations. Together, the potential of porcine MSCs for xenogenous use in human liver therapy is promising but needs further evaluation prior to clinical use.

Adipose-Derived Stem Cells Protect Ischemia-Reperfusion and Partial Hepatectomy by Attenuating Endoplasmic Reticulum Stress

“…Several studies have reported the therapeutic effects of mesenchymal stem cells (MSCs) isolated from the bone marrow and adipose tissues of mice (Tropel et al, 2004;Choi et al, 2014) and rats (Sgodda et al, 2007;Li et al, 2013), and confirmed their ability to differentiate into hepatocytes in vitro (Jiang et al, 2002;Winkler et al, 2015). Although translational research has been conducted on the hepatocyte differentiation of porcine MSCs (Groth et al, 2012), studies on ADSCs are still relatively few (Bosch et al, 2006). The Mesenchymal and Tissue Stem Cell Committee of the International Cell Therapy Association has proposed a minimum defined standard for characterizing human MSCs (Pittenger et al, 1999;Dominici et al, 2006), including adhesion to plastic, multi-directional differentiation ability and expression of distinct surface markers.…”

Comparison of Immunomodulation Properties of Porcine Mesenchymal Stromal/Stem Cells Derived from the Bone Marrow, Adipose Tissue, and Dermal Skin Tissue

“…Therefore, tissue-specific MSCs were shown to have a similar, partial immunomodulating capacity, as the MLR test results did not differ among the tissue-specific MSCs. However, the data from the few available pig xenogeneic MSC-MLR tests are conflicting [ 25 , 26 ]. The reason for the different findings with regard to the immunomodulating capacity of MSCs may be due to use of the t -test method, breed, age, differences in species used, and so forth [ 25 , 26 , 49 ].…”

Mesenchymal Stem Cell-Derived Hepatocytes for Functional Liver Replacement

“…Therefore, investigations in large animal models of liver diseases like in the pig are appreciated to study the behavior of MSC under the given environment produced by the specific disease. In recent times pig models for isolation and transplantation of MSC became available (Casado et al, 2012), which now allow for the evaluation of both the therapeutic and the potential side effects of MSC as close as possible to the human situation (Shi et al, 2010; Groth et al, 2012; Li et al, 2012). …”