Hematopoietic stem cells: basic biology and gene therapy
- Hematopoietic Stem Cell Biology:
We are interested in the basic biology of hematopoietic stem cells. It has been known for decades that hematopoietic stem
cells reside in the bone marrow in a quiescent state and replenish the supply of differentiated cells of the peripheral
blood throughout the lifetime of an animal. No other adult cell type retains the capacity for such immense proliferation
and differentiation. However, little is known about the cells or factors that regulate their primitive state or
control their activation. We study the behavior of these stem cells in vivo and in vitro using mouse stem
cells as a model, as well as pursue the mechanisms which controls their behavior on a molecular level.
- Human Hematopoietic Stem Cells and Gene Therapy:
We also study human hematopoietic stem cells. Human bone marrow stem cells are conventionally defined by their expression of
the antigen CD34. We discovered that a population of putative stem cells exists in adult human bone marrow that may lack
this marker. We are studying these cells in normal and leukemic bone marrow to determine their normal role in human
hematopoiesis. We are also interested in using these cells as vehicles for gene therapy, and thus are determining the most
effective methods to deliver genes to this primitive population.
- Stem Cell Plasticity:
Over the past three years, work from a number of laboratories including our own has led to the idea that stem cells derived
from adult tissues, particularly the hematopoietic system, may be able to differentiate outside their tissue of origin
thereby contributing to regeneration of distal tissues. We study this phenomenon by focusing on a hematopoietically active
stem cell population obtained from murine skeletal muscle, and also by examining the potential of bone marrow-derived
stem cells to differentiate into cardiomyoctes and endothelial cells. Ongoing research seeks to understand the precise
identity of the cells involved in the regeneration process and the mechanisms which regulate their differentiation.
Selected Publications
Jackson KA, Mi T, Goodell MA (1999) Hematopoietic potential of stem cells isolated from
murine skeletal muscle. Proceedings of National Academy of Sciences U.S.A. 96:14482-14486.
McKinney-Freeman SL, Jackson KA, Camargo FD, Ferrari G, Mavilio F, Goodell MA (2002) Muscle-derived
hematopoietic stem cells are hematopoietic in origin. Proceedings of National Academy of Sciences U.S.A.
99:1341-1346.
Welm BE, Tepera SB, Venezia T, Graubert TA, Rosen JM, Goodell MA (2002) Sca-1(pos) cells in the mouse mammary
gland represent an enriched progenitor cell population. Developmental Biology 245:42-56.
Goodell MA (2003) Stem-cell "plasticity": befuddled by the muddle. Current Opinion in Hematology
10:208-13.
Oliveira DM, Goodell MA (2003) Transient RNA interference in hematopoietic progenitors with functional
consequences. Genesis 36:203-208.
Camargo FD, Green R, Capetenaki Y, Jackson KA, Goodell MA (2003) Single hematopoietic stem cells generate
skeletal muscle through myeloid intermediates. Nature Medicine 9:1520-1527.
Norwood K, Wang RY, Hirschmann-Jax C, Andreeff M, Brenner MK, Goodell MA, Wulf GG (2004) An in vivo
propagated human acute myeloid leukemia expressing ABCA3. Leukemia Research 28:295-299.
Camargo FD, Chambers SM, Goodell MA (2004) Stem cell plasticity: from transdifferentiation to macrophage
fusion. Cell Proliferation 37:55-65.
Contact Information
- Margaret A. Goodell, Ph.D.
- Center for Cell and Gene Therapy
- Baylor College of Medicine
- One Baylor Plaza N1030
- Houston, Texas 77030, U.S.A.
- Lab Website
- Tel: (713) 798-1265
- Fax: (713) 798-1230
- E-mail: goodell@bcm.tmc.edu
|
