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Dr. Sagen


 

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The Miami Project
to Cure Paralysis

 

1095 NW 14th Terrace

 

Locator Code R-48

 

Miami, Florida 33136

 

 

Tel:  (305) 243-8185
Fax: (305) 243-3921

 

 

jsagen@med.miami.edu


 

Home Our Research Faculty > Jacqueline Sagen, Ph.D.

 

JACQUELINE SAGEN, PH.D., M.B.A.

Professor, Department of Neurological Surgery

 

 

Cellular Implants for the Alleviation of Chronic Pain and CNS Injury

 

Research Interests

Jacqueline Sagen, Ph.D., M.B.A.

 

The field of neural transplantation has witnessed resurgence due to the potential for cellular implants to provide therapeutic benefits and restore function in the nervous system. Cells implanted into the central nervous system (CNS) can be utilized in several ways: 1) as living cellular minipumps, providing a continually renewable supply of naturally derived therapeutic molecules such as neurotransmitters or trophic factors; 2) as supportive matrices or bridges for axonal regrowth; 3) as replacement of lost neuronal populations consequent to neurological injury or disease. Our laboratory uses all of these neural transplantation strategies in order to explore more promising approaches in the treatment of debilitating CNS disorders.

 

Particularly amenable to the minipump approach are chronic pain syndromes, which require long-term therapeutic management. Research in my laboratory has indicated that cellular implants in the spinal subarachnoid space can alleviate many symptoms of chronic pain in animal models. For these studies, chromaffin cells from the adrenal medulla have been utilized as a graft source because these cells produce a cocktail of agents - including opioid peptides, catecholamines, endogenous NMDA antagonists, and trophic factors - which can reduce pain when administered directly into the spinal fluid. Results from animal studies have led to the initiation of clinical trials at several centers in patients with intractable pain, with encouraging results. However, before large-scale implementation, several issues need to be addressed, particularly the identification of more practical and improved sources of donor cells such as xenografts or engineered cell lines. This is a current focus of research in my laboratory. If successful, the findings from these studies could lead to novel therapies in the long-term management of chronic pain syndromes, particularly for patients refractory to traditional pharmacotherapies, who would benefit greatly by improved quality of life free from pain.

 

Another current research focus utilizes the cellular replacement approach in order to restore function following spinal cord and brain injury. An emergent breakthrough in recent years was the discovery that stem cells possessing the capacity to generate new neural cells and replace lost cellular populations exist in the CNS. Like stem cells identified in other biological systems, neural stem cells are capable of self-renewal, proliferation, and generation of a large number of progeny. In addition, these cells have the capacity to give rise to progenitor neural cell lineages appropriate for their location and metabolic circumstances when exposed to microenvironmental cues, and have been demonstrated to differentiate in vitro into the three major neural phenotypes: neurons, astrocytes, and oligodendrocytes. However, when transplanted to the adult CNS, neuronal differentiation is limited, possibly due to the lack of developmental cues present in the embryonic environment normally encountered by these cells. Thus, additional manipulations, such as exposure to trophic factors, genetic engineering, and/or cellular pre-differentiation will likely be necessary. Our laboratory is exploring the use of neural stem cell transplants for spinal cord injury, traumatic brain injury, and chronic pain. For each of these applications, unique strategies will be required for distinctive cellular populations. Our current strategies for neural stem cell transplantation in spinal cord injury include genetic premodification, co-grafting with trophic factor-producing cells, and combinations with axonal bridges in order to promote more complete restoration of spinal circuitry.

 

In summary, the overall aim of research in my laboratory is the utilization of neural transplants to restore quality of life and alleviate suffering from the most devastating of human disorders resulting from injury to the nervous system.

 

 

 
 
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