Stem Cell Biology and Gene Therapy

Basic Science Research Basic Science Research      


Stem Cell Biology and Gene Therapy
  Mission Statement:
Directed by Dr. Alan Fine, MD, the Stem Cell Biology Program at the Boston University Pulmonary Center consists of a team of basic scientists and pulmonologists who conduct state-of-the-art research focused on the characterization and biology of lung stem cells in the adult and embryonic mouse lung. The long- term objectives of our work are to develop cell-based therapies to regenerate lung tissue after injury, and to clarify the aberrant roles of stem cells in the pathogenesis of lung disease. Our research program also interacts with other research programs on campus affiliated with the Boston University Center for Regenerative Medicine (CReM).     

Background and Interests:
The Stem Cell Biology Program of the Pulmonary Center focuses on identifying stem cell populations that are involved in, or have the capacity to assume differentiated lung cell phenotypes. Our long-term goal is to develop novel cell based strategies for the reconstitution of diseased lung tissue. Currently, we are focused on isolating stem cells from the lung itself, or from the bone marrow and blood. A significant challenge for this type of work is the overall rarity of stem cells. In some tissues, these cells may be present at a frequency of 1:10,000-10,000,000 cells. In view of this, one central focus of our work is the development of novel techniques to purify these very rare cells from tissues.

Through these studies, we hope to localize and identify previously unrecognized types of resident lung stem cells in the adult and embryo. To do this, we utilize a strategy that is based on observations indicating that all stem cells, no matter what their source, share certain characteristics. These include expression of cell surface proteins and an ability to pump out vital dyes. By isolating and characterizing cells with these properties, we hope to establish these cells’ roles in the biology of lung development and tissue homeostasis.

Gene Therapy and Reprogramming Somatic Cells:

Somatic cells, such as skin fibroblasts, can be ‘reprogrammed’ toward a pluripotent state using four lentivirally-delivered transcription factors (Oct4, Klf4, Sox2, and c-myc). These so-called ‘induced pluripotent stem (iPS) cells’ generated through this method are nearly indistinguishable from embryonic stem cells and are genetically identical to the donor from which they are derived. This has raised the exciting possibility of employing iPS cells as autologous cell-based therapies or ex vivo experimental models for a variety of degenerative or inherited diseases. Investigators in our stem cell program are developing novel methods for the derivation and differentiation of iPS cells for future cell therapies designed to reconstitute damaged lung epithelial cells. Please click here to learn more about our iPS cell-related research, including our campus-wide iPS cell bank and vector core: www.bumc.bu.edu/stemcells/crm-core-facilities 

The stem and progenitor cell types currently studied in our program include:

  1. hematopoietic stem cells
  2. mesenchymal stem cells
  3. lung SP cells
  4. embryonic stem  (ES) cells
  5. induced pluripotent stem (iPS) cells

The Stem Cell Biology Group consists of:

Principal Investigators:
Alan Fine, MD, Professor
Wellington Cardoso, MD, PhD, Professor
Darrell N. Kotton, MD, Associate Professor
Maria I. Ramirez, PhD, Associate Professor
Ross Summer, MD, Assistant Professor
Andrew Wilson, MD, Assistant Professor

Post-Doctoral Fellows:
Shamik Ghosh, Ph.D.
Jesus Cabrera, Ph.D.
Aba Somers, MD
Laertis Ikonomou, Ph.D. 

Students:
Tyler Longmire
Constantina Christodoulou
Chris Ford

Technicians/Lab Managers:
Amel Omari
Letty Kwok

Links:
Pulmonary Developmental Biology Group
BU Center for Regenerative Medicine (CReM)
Kotton Lab

Selected Publications:

  1. Summer, R., Fitzsimmons K, Murphy, J, and Fine, A. “Isolation and Characterization of an Adult Lung Mesenchymal Progenitor Cell”.  Am J Respir Cell Mol Biol. 2007 Aug;37(2):152-9.
  2. Murphy, J., Summer, R., Wilson , A.A., Kotton, D.N., and Fine, A. “The Prolonged Life-Span of Alveolar Macrophages”. Am. J Resp Cell Mol Biol 38 : 380-385, 2008.
  3. Wilson AA, Kwok LW, Hovav AH, Ohle SJ, Little FF, Fine A, Kotton DN. “ Sustained Expression of a 1-antitrypsin After Transplantation of Manipulated Hematopoietic Stem Cells”. Am J Respir Cell Mol Biol . 39 ( 2 ): 133-41. Aug 2008.
  4. Kotton DN, Fine A. “Lung Stem Cells”. Cell & Tissue Research . 331 ( 1 ): 145-56. Jan 2008
  5. Chang, JC, Summer R, Sun X, Fitszimmons, Fine A. “Evidence that Bone Marrow Cells Do Not Contribute to the Alveolar Epithelium.” Am J Respir Cell Mol Biol. 33: 335-342. October 2005.
  6. Mostoslavsky G, Kotton DN, Fabian AJ, Grey JT, Mulligan RC. “Efficiency of transduction of highly purified hematopoietic stem cells by lentiviral and retroviral vectors under conditions of minimal in vitro manipulation.” Molecular Therapy 11(6):932-40. June 2005.
  7. Summer R, Kotton DN, Liang S, Fitzsimmons K, Sun X, Fine A. “Embryonic lung side population cells are hematopoietic and vascular precursors”. Am J Respir Cell Mol Biol. 33:32-40. July 2005.
  8. Summer R, Kotton DN, Sun X, Fitzsimmons K, and Fine A. “The Origin and Phenotype of Lung Side Population Cells.” Am J Physiol Lung Cell Mol Physiol. Mar 2004.
  9. Summer R, Kotton DN, Sun X, Ma B, Fitzsimmons K, Fine A. “Side population cells and Bcrp1 expression in lung.” Am J Physiol Lung Cell Mol .
  10. Kotton DN, Ma BY, Cardoso, WV, Sanderson EA, Summer, RS, Williams MC, and Fine A. “Bone Marrow-Derived Cells as Progenitors of Lung Alveolar Epithelium.” Development 128: 5181-5188. December 2001.
 

 

Primary teaching affiliate
of BU School of Medicine