Biology of Adult Stem Cells from the Bone Marrow
This program is designed to study and discover the rules and factors that govern expansion and differentiation of multipotential stem cells from bone marrow.
A central question in the field of adult stem cell biology is defining the characteristics of multi-potent stem cells including the bone marrow cells harvested from adults. As yet no definite biomarkers have been identified; therefore, much like embryonic stem cells, the isolation of adult stem cells rely on the enrichment methods in culture and precise expansion and differentiation protocols.
In our laboratories, non-hematopoietic stem cells were separated from the hematopoietic components in culture by virtue of their size and adherence to plastic. These cultures yielded a variety of cells with different morphologies and abilities for differentiation and proliferation. A number of in vivo and in vitro studies have shown that these cells express neural markers. We plan to perform further animal studies to assess the potential of these cells as to what type of neural tissues they are capable of generating. Another issue is to define the factors that govern the fate of these cells in vivo. These will be carried out in immune-compromised and developing animals as a preamble to trials in primates and later clinical trials.
Our research program involves cell therapy and gene therapy for treatment of Parkinson disease, with special emphasis on the use of bone marrow stem cells, perhaps from a patient's own marrow. Also, we are investigating the molecular mechanisms underlying the genesis of this disease.
Neurodegenerative diseases, including Parkinson disease, involve loss of cells in selected areas of the brain. We have been able to isolate, expand and genetically engineer stem-like cells from the bone marrow. The genetically engineered cells are capable of producing tyrosine hydroxylase. We plan to differentiate human marrow stromal cells into dopaminergic cells and perform the necessary animal and preclinical studies on these genetically engineered cells to reach the human trial stage for treatment of Parkinson disease . The majority of experiments on the rodent model of Parkinson disease have already been carried out. Further experiments on rodents with novel methods of gene engineering are currently in progress in our laboratory.
We have embarked on a number of studies that will shed light on the molecular, developmental and perhaps viral factors responsible for genesis of glial tumors.
Another goal of the Temple Neurology laboratories is to study the pathophysiology and methods of treatments of brain tumors. It is now known that neural stem cells pursue and stalk glioma cells in the advancing margin of brain tumor. Again, the goal is to perform the necessary studies to reach the clinical trial stage. We will use genetic engineering to manufacture tumor suppressing molecules and apply to the animal models of brain tumor. We have already generated a rat model of glioma, and these experiments should proceed without delay. In another set of studies, we have been studying the mechanisms of tumor genesis.
The above models serve as a way to test the universality of the use of stem cells from adults for treatment of neurological diseases. These diseases can include stroke and spinal cord injury, and the production of growth factors by the stem cells for treatment of ALS, Alzheimer's and other neurologic diseases.
Temple's Department of Neurology participates in a variety of drug trials and other clinical research. Lewis Katz School of Medicine at Temple University's General Clinical Research Center is located adjacent to the Neurology floor in Temple University Hospital, and a number of neuro-related projects are carried out in this Center. For a listing of active clinical research trials, please click on the Active Clinical Trials link to the right of this page.