Adult Stem Cell Research
LFA Research Program | Grants, Fellowships and Special Initiatives | LFA Peer-Review Research Grants Program | Adult Stem Cell Research
Research Objectives:
To advance basic and clinical adult stem cell transplantation research in humans as a treatment for lupus.
These grant awards are made possible through support by the Cooper Family Foundation
"Unusual Regulatory T Cells in Patients with Severe Lupus Following HSCT"
Richard Burt, M.D.
Chief, Division of Immunotherapy
Northwestern University (IL)
Lay Abstract:
Researchers at Northwestern University have found that regulatory T cells (Treg) return in patients with refractory lupus after stem cell transplantation, and both CD4+CD25HighFoxP3+, and an unusual CD8+FoxP3+ Treg subsets are increased. Observations in mouse models of SLE suggest that induced CD8+ Treg cells are important in controlling lupus. Researchers aim to characterize the CD8 Treg subset of post-transplant lupus patients with regards to their unique surface markers, cytokine/chemokine profile, and mechanism of action. Clinical correlations based on gender and disease activity will be done. Molecular requirements for both nuclear autoantigen-specific and non-specific suppressive function of the Treg will be determined. Significance to gaps in knowledge relevant to lupus. The mechanisms of long-term remission of lupus after stem cell transplantation are unknown. Our hypothesis is that the therapy generates a newly differentiated population of Treg cells, which repairs the Treg deficiency in lupus. Defects in Treg cells are beginning to be described in lupus patients. Most of those studies deal with phenotyping and enumerating the CD4+CD25High Treg subset by surface markers. Functional studies, especially autoantigen-specific suppression have not been done. Moreover, very little is known about unusual CD8+ Treg cells in humans and how they could control lupus autoimmunity, although animal models indicate their importance. Investigators will evaluate the quality and quantity of Treg cells before and after HSCT and compare their recovery to gender and clinical disease status. Therefore, this proposal will address new issues critical for immunoregulation of lupus autoimmunity and therapy.
"Induced Pluripotent Stem (iPS) Cell-Based Therapy for SLE"
Igor Slukvin, M.D., Ph.D.
Assistant Professor
University of Wisconsin, Madison
Lay Abstract:
The major goal of this proposal is to significantly advance the stem cell-based therapies for drug-resistant lupus through development of novel technologies for generation of HSCs and immunotherapeutic cells from induced pluripotent cells (iPSCs). The iPSCs are stem cells artificially derived from somatic fibroblasts through insertion of genes critical for the maintenance of pluripotency. These cells can be generated from SLE patients and differentiated into blood cells. Because iPSCs and sustainably expanded and genetically altered in a highly controlled way that is not yet possible with more committed HSCs, iPSCs could provide important advantages over somatic HSCs as target cells for stem cell based therapy of SLE. In this application we propose to characterize in vivo repopulating potential of primitive hematopoietic cells derived from iPSCs, develop a system for differentiation of iPSCs into dendritic cells and T cells, and demonstrate the feasibility of iPSC-based gene transfer into hematopoietic cells. The proposed studies could ultimately lead to novel adult stem cell-based and gene therapies for SLE.
View the past recipients of this award
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