
Twisting immune responses for allogeneic stem cell therapy
Author(s) -
Shengwen Calvin Li,
Jiang Zhong
Publication year - 2009
Publication title -
world journal of stem cells
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 18
ISSN - 1948-0210
DOI - 10.4252/wjsc.v1.i1.30
Subject(s) - stem cell , immune system , immunology , antigen , embryonic stem cell , haematopoiesis , progenitor cell , biology , immune tolerance , cancer research , medicine , microbiology and biotechnology , biochemistry , gene
Stem cell-derived tissues and organs have the potential to change modern clinical science. However, rejection of allogeneic grafts by the host's immune system is an issue which needs to be addressed before embryonic stem cell-derived cells or tissues can be used as medicines. Mismatches in human leukocyte class I antigens and minor histocompatibility antigens are the central factors that are responsible for various graft-versus-host diseases. Traditional strategies usually involve suppressing the whole immune systems with drugs. There are many side effects associated with these methods. Here, we discuss an emerging strategy for manipulating the central immune tolerance by naturally "introducing" donor antigens to a host so a recipient can acquire tolerance specifically to the donor cells or tissues. This strategy has two distinct stages. The first stage restores the thymic function of adult patients with sex steroid inhibitory drugs (LHRH-A), keratinocyte growth factor (KGF), interleukin 7 (IL-7) and FMS-like tyrosine kinase 3 (FLT3). The second stage introduces hematopoietic stem cells and their downstream progenitors to the restored thymus by direct injection. Hematopoietic stem cells are used to introduce donor antigens because they have priority access to the thymus. We also review several clinical cases to explain this new strategy.