Stem Cells and Cellular Therapy

Hemophilia A results from an insufficiency of factor VIII (FVIII). We are exploring the possibility of a cell-based therapy to treat or cure hemophilia A. Current work is focused on the transplantation of a specialized subset of endothelial cells found in the liver: liver sinusoidal endothelial cells. These cells are the main source of factor VIII.

Selected Publications:

Bárcena A, Muench MO, Kapidzic M, Fisher SJ. A new role for the human placenta as a hematopoietic site throughout gestation. Reprod Sci. 2009;16:178-187. PMC2731631

Bárcena A, Muench MO, Kapidzic M, Gormley M, Goldfien GA, Fisher SJ. Human placenta and chorion: potential additional sources of hematopoietic stem cells for transplantation. Transfusion. 2011;51 Suppl 4:94S-105S. PMC3266842

Muench MO, Chen JC, Beyer AI, Fomin ME. Cellular therapies supplement: the peritoneum as an ectopic site of hematopoiesis following in utero transplantation. Transfusion. 2011;51 Suppl 4:106S-117S. PMC3246414

Muench MO. Stem cells and progenitors in liver development. San Rafael, CA: Morgan & Claypool Life Science Publishers; 2012.

Fomin ME, Zhou Y, Beyer AI, Publicover J, Baron JL, Muench MO. Production of factor VIII by human liver sinusoidal endothelial cells transplanted in immunodeficient uPA mice. PLoS ONE. 2013;8:e77255. PMC3805584

Ye L, Muench MO, Fusaki N, Beyer AI, Wang J, Qi Z, Yu J, Kan YW. Blood cell-derived induced pluripotent stem cells free of reprogramming factors generated by Sendai viral vectors. Stem Cells Transl Med. 2013;2:558-566. PMC3726135

Xie F, Ye L, Chang JC, Beyer AI, Wang J, Muench MO, Kan YW. Seamless gene correction of β-thalassemia mutations in patient-specific iPSCs using CRISPR/Cas9 and piggyBac. Genome Res. 2014;24:1526-1533. PMC4158758

Fomin ME, Togarrati PP, Muench MO. Progress and challenges in the development of a cell-based therapy for hemophilia A. J Thromb Haemost. 2014;12:1954-1965. PMC4388483

Bárcena A, Muench MO, Kapidzic M, Gormley M, Fisher SJ. The Human Term Placenta as a Source of Transplantable Hematopoietic Stem Cells. In: Atala A, Murphy SV, editors. Perinatal Stem Cells Springer New York; 2014. p. 171-81.

Muench MO, Beyer AI, Fomin ME, Thakker R, Mulvaney US, Nakamura M, Suemizu H, Bárcena A. The adult livers of immunodeficient mice support human hematopoiesis: evidence for a hepatic mast cell population that develops early in human ontogeny. PLoS ONE. 2014;9:e97312. PMC4018295

Mahajan MM, Cheng B, Beyer AI, Mulvaney US, Wilkinson MB, Fomin ME, Muench MO. A quantitative assessment of the content of hematopoietic stem cells in mouse and human endosteal-bone marrow: a simple and rapid method for the isolation of mouse central bone marrow. BMC Hematol. 2015;15:9. PMC4496931

Kulis M, Merkel A, Heath S, Queirós AC, Schuyler RP, Castellano G, Beekman R, Raineri E, Esteve A, Clot G, Verdaguer-Dot N, Duran-Ferrer M, Russiñol N, Vilarrasa-Blasi R, Ecker S, Pancaldi V, Rico D, Agueda L, Blanc J, Richardson D, Clarke L, Datta A, Pascual M, Agirre X, Prosper F, Alignani D, Paiva B, Caron G, Fest T, Muench MO, Fomin ME, Lee ST, Wiemels JL, Valencia A, Gut M, Flicek P, Stunnenberg HG, Siebert R, Küppers R, Gut IG, Campo E, Martín-Subero JI. Whole-genome fingerprint of the DNA methylome during human B cell differentiation. Nat Genet. 2015;47:746-756.

Lee ST, Muench MO, Fomin ME, Xiao J, Zhou M, de Smith A, Martín-Subero JI, Heath S, Houseman EA, Roy R, Wrensch M, Wiencke J, Metayer C, Wiemels JL. Epigenetic remodeling in B-cell acute lymphoblastic leukemia occurs in two tracks and employs embryonic stem cell-like signatures. Nucleic Acids Res. 2015;43:2590-2602. PMC4357708

Suzuki S, Sargent RG, Illek B, Fischer H, Esmaeili-Shandiz A, Yezzi MJ, Lee A, Yang Y, Kim S, Renz P, Qi Z, Yu J, Muench MO, Beyer AI, Guimarães AO, Ye L, Chang J, Fine EJ, Cradick TJ, Bao G, Rahdar M, Porteus MH, Shuto T, Kai H, Kan YW, Gruenert DC. TALENs Facilitate Single-step Seamless SDF Correction of F508del CFTR in Airway Epithelial Submucosal Gland Cell-derived CF-iPSCs. Mol Ther Nucleic Acids. 2016;5:e273.

Ye L, Wang J, Tan Y, Beyer AI, Xie F, Muench MO, Kan YW. Genome editing using CRISPR-Cas9 to create the HPFH genotype in HSPCs: An approach for treating sickle cell disease and β-thalassemia. Proc Natl Acad Sci U S A. 2016;113:10661-10665.

Beyer AI, Muench MO. Comparison of human hematopoietic reconstitution in different strains of immunodeficient mice. Stem Cells Dev. 2017;26:102-112.

Muench MO, Kapidzic M, Gormley M, Gutierrez AG, Ponder KL, Fomin ME, Beyer AI, Stolp H, Qi Z, Fisher SJ, Bárcena A. The human chorion contains definitive hematopoietic stem cells from the fifteenth week of gestation. Development. 2017;In Press.