Copyright ©2009 Baishideng. All rights reserved
World J Stem Cells. Dec 31, 2009; 1(1): 30-35
Published online Dec 31, 2009. doi: 10.4252/wjsc.v1.i1.30
Twisting immune responses for allogeneic stem cell therapy
Shengwen Calvin Li, Jiang F Zhong
Shengwen Calvin Li, CHOC Children’s Hospital Research Institute, University of California Irvine, 455 South Main Street, Orange, California, CA 92868, United States
Jiang F Zhong, Department of Pathology, University of Southern California, School of Medicine, 2025 Zonal Avenue, Los Angeles, California, CA 90033, United States
Author contributions: Li SC drafted the manuscript; Li SC and Zhong JF revised the paper.
Supported by CHOC Children’s Foundation and CHOC Neuroscience Institute (to Li SC) and NIH grant 1R21CA134391-01A1 (to Zhong JF)
Correspondence to: Shengwen Calvin Li, PhD, Head of Neuro-Oncology Research Laboratory, CHOC Children’s Hospital, University of California Irvine, 455 South Main Street, Orange, California, CA 92868, United States. sli@choc.org
Telephone: +1-714-2894964 Fax: +1-714-5164318
Received: September 8, 2009
Revised: October 21, 2009
Accepted: October 28, 2009
Published online: December 31, 2009

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.

Keywords: Stem cell therapy, Immune response, Allogeneic grafts