[Frontiers in Bioscience 11, 899-907, January 1, 2006]

Homing genes, cell therapy and stroke

Woei-Cherng Shyu 1, Yih-Jing Lee 2, Demeral David Liu 1, Shinn-Zong Lin 1 and Hung Li 3

1 Neuro-Medical Scientific Center, Tzu-Chi Buddhist General Hospital, Tzu-Chi University, Hualien, Taiwan, 2 School of Medicine, Fu-Jen Catholic University, Taipei, Taiwan, 3 Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Recent studies about stem-cell based therapy
4. Mechanisms that alleviate stroke symptoms in G-CSF therapy
5. Homing factors
6. Stromal cell-derived factor 1 and CXC chemokine receptor 4
7. When is "homing" possible?
8. How do stem cells function at the site of ischemia?
9. Conclusion
10. Acknowledgements
11. References

1. ABSTRACT

Stem cell therapies, such as bone marrow transplantation, are a promising strategy for the treatment of stroke. Bone marrow-derived stem cells (BMSCs) including both hematopoietic and mesenchymal stem cells (HSCs and MSCs) can exhibit tremendous cellular differentiation in numerous organs. BMSCs may also promote structural and functional repair in several organs such as the heart, liver, brain, and skeletal muscle via stem cell plasticity. Interestingly, ischemia is known to induce mobilization of BMSCs in both animal models and humans. The tissue injury is "sensed" by the stem cells and they migrate to the site of damage and undergo differentiation. The plasticity, differentiation, and migratory functions of BMSCs in a given tissue are dependent on the specific signals present in the local micro-environment of the damaged tissue. Therefore, the ischemic micro-environment has critical patho-biological functions that are essential for the seeding, expansion, survival, renewal, growth and differentiation of BMSCs in damaged brain remodeling. Recent studies have identified the specific molecular signals, such as SDF-1/CXCR4, required for the interaction of BMSCs and damaged host tissues. Understanding the exact molecular basis of stem cell plasticity in relation to local ischemic signals could offer new insights to permit better management of stroke and other ischemic disorders. The aim of this review is to summarize recent studies into how BMSCs reach, recognize, and function in cerebral ischemic tissues, with particular regard to phenotypical reprogramming of stem cells, or "stem cell plasticity".