The low availability of functional hepatocytes has been an unmet demand for basic scientific research, new drug development, and cell-based clinical applications for decades. Because of the inability to expand hepatocytes in vitro, alternative sources of hepatocytes are a focus of liver regenerative medicine. We report a new group of blood-derived CD34+ progenitor cells (BDPCs) that have the ability to expand and differentiate into functional hepatocyte-like cells and promote liver regeneration. BDPCs were obtained from the peripheral blood of an adult mouse with expression of surface markers CD34, CD45, Sca-1, c-kit, and Thy1.1. BDPCs can proliferate in vitro and differentiate into hepatocyte-like cells expressing hepatocyte markers, including CK8, CK18, CK19, a-fetoprotein, integrin-b1, and A6. The differentiated BDPCs (dBDPCs) also display liver-specific functional activities, such as glycogen storage, urea production, and albumin secretion. dBDPCs have cytochrome P450 activity and express specific hepatic transcription factors, such as hepatic nuclear factor 1a. To demonstrate liver regenerative activity, dBDPCs were injected into mice with severe acute liver damage caused by a high-dose injection of carbon tetrachloride (CCl4). dBDPC treatment rescued the mice from severe acute liver injury, increased survival, and induced liver regeneration. Because of their ease of access and application through peripheral blood and their capability of rapid expansion and hepatic differentiation, BDPCs have great potential as a cell-based therapy for liver disease. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:723–732
Academia and industry partner to advance liver tissue models
The University of California, San Diego School of Medicine and Samsara Sciences, Inc. (both CA, USA) will collaborate on the development of techniques to isolate and characterize liver cells. They hope to drive insights into liver biology, drug safety and efficacy, and the treatment of liver disease.
The University of California, San Diego School of Medicine and Samsara Sciences, Inc. (both CA, USA) are joining forces to develop techniques to isolate and characterize liver cells, in order to gain liver biology insights, drive drug safety and efficacy, and generate treatments for liver disease.
The University of California, San Diego Medical School scientists will generate protocols for the isolation of specialized human liver cells. Additionally, they will extensively characterize the phenotype and function of these cells in a range of laboratory and animal models. Samsara (a subsidiary of Organovo Holdings, Inc.) will subsequently focus on the commercial supply of specialized cells for applications in bioprinted tissues, among other cell-based models.
"This is a unique arrangement," explained Tatiana Kisseleva (UC San Diego Medical School). "Samsara's resources will allow us to generate high-quality cells to conduct translational research on liver injury, cirrhosis and cancer, while Samsara benefits from our expertise in liver cell isolation and characterization."
Instead of focusing on the more intensively studied hepatocytes, the groups will include other supporting cells within the liver. Studies are revealing that the presence of these supporting cells, in an arrangement of relevance to the human body, significantly affect the performance and function of liver cells in laboratory experiments.
"We formed Samsara based on repeated observations that the functional performance of cell-based models is dependent to a large degree on the quality and phenotype of the input cells being used," commented Sharon Presnell (Samsara Sciences). "We're extremely excited to be working with Dr Kisseleva. As a leading expert in liver cell biology, she is well positioned to develop isolation and characterization strategies that yield stellate and other support cells that are ideally suited for use in 3D-bioprinted tissue applications."