E. Scott Swenson M.D., Ph.D.

Assistant Professor
Section of Digestive Diseases

Research Interests

I am investigating the role of stem and progenitor cells in the liver during normal development and in response to liver injury. The liver's remarkable capacity for regeneration after injury suggests that a better understanding of these phenomena will lead to novel cell therapy and regenerative medicine approaches to acute and chronic liver disease. Under some conditions, cells arising from the bone marrow may also contribute to liver regeneration.

Male marrow-derived hepatocytes in a female recipient mouse, six months after sex-mismatched bone marrow transplantation and in vivo metabolic selection

The Y chromosome (pink dots) colocalizes with HNF-1 (green nuclei). Nuclei are counterstained with DAPI (blue). The recipient mouse had a homozygous targeted mutation in the Fumaryl acetoacetate hydrolase (FAH) gene, which models the human liver disease, Hereditary Tyrosinemia. Transplantation of normal bone marrow results in extensive repopulation of normal hepatocytes in the tyrosinemic liver. The presence of two or more Y chromosomes in some hepatocytes is consistent with the normal phenomenon of hepatocyte polyploidy.

Ongoing studies will address the issue of whether stable in vivo fusion of cells of hematopoietic origin, such as Kupffer cells, with injured hepatocytes always accounts for the apparent developmental "plasticity" of bone marrow-derived cells.

Selected Publications

• Cirrhosis and portal hypertension (2004). Chap. 45 in Field Guide to Internal Medicine. ES Swenson. Lippincott, Williams and Wilkins, Philadelphia, PA.
• Dose and time-dependent oval cell reaction in acetaminophen-induced murine liver injury (2005). AV Kofman, G Morgan, A Kirschenbaum, J Osbeck, M Hussain, S Swenson and ND Theise. Hepatology 41(6): 1252-126.
• Engraftment of bone marrow derived epithelial cells (2005). JS Van Arnam, E Herzog, J Grove, E Bruscia, E Ziegler, S Swenson, DS Krause. Stem Cell Reviews 1:21-28.
• Limitations of green fluorescent protein (GFP) as a cell lineage marker (2007). ES Swenson, JG Price, T Brazelton, DS Krause. Stem Cells 25: 2593-2600.
• Induced pluripotent cells mimicking human embryonic stem cells. M Mohamadnejad M, ES Swenson (2008). Arch Iran Med. 11:125-8.
• Physiologic variations in stem cell factor and stromal-derived factor-1 in murine models of liver injury and regeneration (2007). ES Swenson, R Kuwahara, DS Krause, ND Theise. Liver International 28: 308-318.
• The hepatic stem cell niche: identification by label retaining cell assay. (2008). R Kuwahara, AV Kofman, CS Landis, ES Swenson, E Barendswaard, ND Theise ND. Hepatology 47:1994-2002.
• Hepatocyte nuclear factor-1 as marker of hepatic epithelial phenotype reveals bone marrow-derived hepatocytes, but not oval cells, after liver injury in mice (2008). ES Swenson, I Guest, Z Ilic, M Mazzeo, P Lizardi, C Hardiman, S Sell, DS Krause. Stem Cells 26:1768-1777.

Contact

Campus Address
Department of Internal Medicine
333 Cedar Street (LMP 1080)
New Haven, CT 06520

E-mail
scott.swenson@yale.edu

Office Phone
(203) 785-2441

Fax
(203) 785-7273