Stem cells have two features: the ability to differentiate along different lineages and the ability of selfrenewal. Two major types of stem cells have been described, namely, embryonic stem cells and adult stem cells. Embryonic stem cells (ESC) are obtained from the inner cell mass of the blastocyst and are associated with tumorigenesis, and the use of human ESCs involves ethical and legal considerations. The use of adult mesenchymal stem cells is less problematic with regard to these issues. Mesenchymal stem cells (MSCs) are stromal cells that have the ability to self-renew and also exhibit multilineage differentiation. MSCs can be isolated from a variety of tissues, such as umbilical cord, endometrial polyps, menses blood, bone marrow, adipose tissue, etc. This is because the ease of harvest and quantity obtained make these sources most practical for experimental and possible clinical applications. Recently, MSCs have been found in new sources, such as menstrual blood and endometrium. There are likely more sources of MSCs waiting to be discovered, and MSCs may be a good candidate for future experimental or clinical applications. One of the major challenges is to elucidate the mechanisms of differentiation, mobilization, and homing of MSCs, which are highly complex. The multipotent properties of MSCs make them an attractive choice for possible development of clinical applications. Future studies should explore the role of MSCs in differentiation, transplantation, and immune response in various diseases.

The human umbilical cord is a promising source of mesenchymal stem cells (HUCMSCs). Unlike bone marrow stem cells, HUCMSCs have a painless collection procedure and faster self-renewal properties. Different derivation protocols may provide different amounts and populations of stem cells. Stem cell populations have also been reported in other compartments of the umbilical cord, such as the cord lining, perivascular tissue, and Wharton's jelly. HUCMSCs are noncontroversial sources compared to embryonic stem cells. They can differentiate into the three germ layers that promote tissue repair and modulate immune responses and anticancer properties. Thus, they are attractive autologous or allogenic agents for the treatment of malignant and nonmalignant solid and soft cancers. HUCMCs also can be the feeder layer for embryonic stem cells or other pluripotent stem cells. Regarding their therapeutic value, storage banking system and protocols should be established immediately. This review critically evaluates their therapeutic value, challenges, and future directions for their clinical applications.

Background-Stroke is a leading cause of death and disability worldwide; however, no effective treatment currently exists. Methods and Results-Rats receiving subcutaneous granulocyte colony-stimulating factor (G-CSF) showed less cerebral infarction, as evaluated by MRI, and improved motor performance after right middle cerebral artery ligation than vehicle-treated control rats. Subcutaneous administration of G-CSF enhanced the availability of circulating hematopoietic stem cells to the brain and their capacity for neurogenesis and angiogenesis in rats with cerebral ischemia. Conclusions-G-CSF induced increases in bone marrow cell mobilization and targeting to the brain, reducing the volume of cerebral infarction and improving neural plasticity and vascularization.

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Stromal cell-derived factor (SDF)-1␣ is involved in the trafficking of hematopoietic stem cells from bone marrow to peripheral blood, and its expression is increased in the penumbra of the ischemic brain. In this study, SDF-1␣ was found to exert neuroprotective effects that rescued primary cortical cultures from H 2 O 2 neurotoxicity, and to modulate neurotrophic factor expression. Rats receiving intracerebral administration of SDF-1␣ showed less cerebral infarction due to up-regulation of antiapoptotic proteins, and they had improved motor performance. SDF-1␣ injection enhanced the targeting of bone marrow (BM)-derived cells to the injured brain, as demonstrated in green fluorescent protein-chimeric mice with cerebral ischemia. In addition, increased vascular density in the ischemic cortex of SDF-1␣-treated rats enhanced functional local cerebral blood flow. In summary, intracerebral administration of SDF-1␣ resulted in neuroprotection against neurotoxic insult, and it induced increased BM-derived cell targeting to the ischemic brain, thereby reducing the volume of cerebral infarction and improving neural plasticity.Stroke is a major cause of mortality worldwide (van Gijn and Dennis, 1998), and bone marrow stem cell transplantation has been demonstrated to be a potential strategy for its treatment (Li et al., 2002). Under ischemic conditions, circulating stem cells seem to selectively migrate to ischemic regions to support the plasticity and functional recovery of damaged tissue (Orlic et al., 2001). However, the signals that guide stem cells to ischemic lesions are as yet unknown. Stromal cell-derived factor (SDF)-1␣, a CXC chemokine produced by bone marrow stromal cells, is a potent chemoattractant for hematopoietic stem cells (HSCs), and it is constitutively expressed by all tissues (Shirozu et al., 1995). Recent reports have indicated that SDF-1␣ is a strong chemoattractant for CD34 ϩ cells, which express CXCR4, the receptor for SDF-1␣, and play an important role in HSC trafficking between peripheral circulation and bone marrow (Petit et al., 2002). Studies of mice lacking SDF-1␣ or CXCR4 have confirmed that SDF-1␣ is necessary for the migration of HSCs from fetal liver to bone marrow (Zou et al., 1998). In addition, the expression of SDF-1␣ in the brains of human immunodeficiency virus (HIV)-positive patients suggests that SDF-1␣ may play a role in neuroprotection in response to HIV infection (Langford et al., 2002). Therefore, SDF-1␣/CXCR4 signaling may also play an important neuroprotective/neuroplastic role in the repair of neural tissue injury.Expression of CXCR4 and SDF-1␣ after focal cerebral ischemia (Stumm et al., 2002) led us to speculate that this chemokine may also signal adhesion and migration of HSCs to ischemic tissue. On this basis, we hypothesized that locally This work was supported in part by Chen-Han Foundation for Education, Academia Sinica Grant 94M003 and National Science Council Grant NSC95-2745-B-001-001-MY3.Article, publication date, and citation information can be found at...

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