|Department Affiliations||Stem Cell Program in Institute for Cell Engineering, Edythe Harris Lucas and Clara Lucas Lynn Chair in Hematology Associate Director for Basic Research, Johns Hopkins Hematology|
|SOM Address||747 Miller Research Building|
Human stem cell biology and engineering, and their applications for regenerative medicine For biological studies, Dr. Cheng’s laboratory is focusing on stem cell self-renewal and hematopoietic (blood-forming) development. This lab is among the first in Hopkins and USA (since January 2002) to use human embryonic stem (ES) cells as a new model for biomedical research as well as to explore their use for novel cell replacement therapy. They found that selected human postnatal cells such as human mesenchymal stem cells/marrow stromal cells (MSCs) can replace previously required mouse embryonic fibroblasts in supporting the growth of human ES cells (1). This study provides a foundation to elucidate growth factors and mechanisms required for maintaining pluripotent human ES cells in culture (2). This lab also uses human ES cells as well as postnatal human hematopoietic stem cells (HSCs) to study human hematopoiesis and to improve HSC transplantation (3, 4). They recently demonstrated that in vitro differentiated human hES cells generate functional antigen-presenting cells, in addition to other myeloid and erythroid cells (5). This study provides a foundation for ongoing projects to study human hematopoiesis using human ES cell lines with or without defined genetic modifications.
For “bio-engineering” projects, they take the advantage of their expertise of using lenti-vectors for transgene expression. This allows them to develop new genetic technologies applicable to human cells, which could not benefit from transgenic animal techniques. In addition to gene therapy, lenti-vectors provide a powerful research tool to stably express a transgene or siRNA to modulate gene expression in essentially any cell types including human stem cells (3-4, 6). In addition to lenti-vectors that can serve as insertional mutagens, they also use other genetic tools to create engineered human ES cells containing specific mutations found in human genetic diseases. These mutated human ES cells and their in vitro differentiation systems may provide a better experimental model for understanding and treating human diseases, particularly those lacking a prospective experimental model.
• Cheng L, Hammond H, Ye Z, Zhan X, and Dravid G (2003). Human adult marrow cells support prolonged expansion of human embryonic stem cells in culture. Stem Cells, 20:121-132.
• Dravid G, Ye Z, Hammond H, Chen G, Pyle A, Donovan PJ, Yu X and Cheng L (2005). Defining the role of Wnt/beta-catenin signaling in the survival, proliferation and self-renewal of human embryonic stem cells. Stem Cells, 23: 1489-1488.
• Cui Y, Golob J, Kelleher E, Ye Z, Pardoll D, and Cheng L (2002). Targeting transgene expression to antigen presenting cells derived from lentivirus transduced, engrafting human hematopoietic stem/progenitor cells. Blood, 99, 399-408.
• Yu X, Zhan X, D’Costa J, Tanavde VM, Ye Z, Peng T, Malehorn MT, Yang X, Civin CI and Cheng L (2003). Lentiviral Vectors with Two Independent Internal Promoters Transfer High-Level Expression of Multiple Transgenes to Human Hematopoietic Stem-Progenitor Cells. Molecular Therapy, 7: 827-838.
• Zhan X, Dravid G, Ye Z, Hammond H, Shamblott M, Gearhart J, and Cheng L (2004). Functional antigen-presenting leukocytes derived from human embryonic stem cells in vitro. The Lancet, 363: 163-171.
• Ye Z and Cheng L (2003). Making lentiviral vectors more powerful and universal (a review). Discovery Medicine, 3:48-49.