Advances in Translational Stem Cell Research and Therapies

Scientific Scopes of Pan Pacific Symposium on Stem Cells Research (PPSSCR): Treating Diseases by Using Stem Cells, Genes and Biomaterials

In April 2009 the Pan Pacific Symposium on Stem Cells Research (PPSSCR) held its second annual meeting in Taichung, Taiwan. The main purpose of the PPS SCR is to promote translational cell therapy in various diseases, which include the fields of neurology, hematology, cardiology, orthopedics, dermatology, hepatology, metabolitics, etc. The cells discussed mainly are related to adult stem cells, umbilical cord blood stem cells, embryonic stem cells (ES cells), induced pluripotent stem cells (iPS), and progenitor cells. These stem cells may translate directly into clinical use or in combination with biomaterials or nanoparticles. Stem cells may also carry specific genes for treating congenital diseases. At the 2009 meeting, research on a number of translational cell therapeutics was presented: for example, cord blood stem cell transplantation in thalassemia major, and CD34 stem cell therapy in chronic stroke patients. Comparison of this issue devoted to the 2009 meeting to the previously published issue devoted to the 2008 meeting (13) can reveal how some topics are advancing. These current translation stem cell technologies are discussed by outstanding stem cell scientists and clinicians all over the world.

Four Important Fields of Stem Cell Medicine: Stem Cell Sources, Culture and Expanding Technologies, Translational Technologies, and Cancer Stem Cells

In this issue, we highlight four important fields relevant to translational stem cell research. These are summarized as follows.

Stem Cells Sources

Different types of stem cells can be derived from different sources. In this issue there is a review looking at the various sources of mesenchymal stem cells including menstrual blood and the endometrium, and their future application in treating diseases (4), as well as a review on iPS cells. The latter describes different methods for producing these cells and comparing the advantages and limitations of each strategy in the context of their future clinical application (15). The relationship between the subventricular zone and reproductive function is reviewed in a third article with respect to the production of endogenous neural stem cells (11).

Articles on some of these types of cells can also be found in the translational technologies section from this issue and the previous special issue devoted to the 2008 PPSSCR.

Culture and Expanding Technology

There are a number of different ways of expanding stem cell cultures and this issue includes a number of reviews on this topic. For instance, Fu et al. highlight ways to culture stem cells using specially designed biomaterial culture systems (7), whereas Sun et al. describe different microcarrier-based suspension culture systems (19). By comparison, Hung et al. highlight mechanisms triggered by the interaction of endothelial progenitor cells and nanobiomaterial-derived vascular tissue substitutes, composed of matrix, peptides, and growth factors that can act as scaffolds for the generation of new vascular tissue (8).

This compares with the previous PPSSCR meeting at which Liu et al. reported on the regulation of micro-RNA (miRNA) in hematopoietic stem cells, mesenchymal stem cells, endothelial progenitor cells, neural progenitor cells, as well as iPS cells and how these cell-intrinsic regulators can affect the maintenance, self-renewal, development, and differentiation of the stem cells (16). In addition, Fu et al. previously introduced the modern concept of using alternative splicing to produce iPs cells and stem cell differentiation (6). A third report focused on the use of nanotechnology for controlling the proliferation, elongation, differentiation, and motivation of stem cells in vitro and in vivo (the brain and spinal cord) by using self-assembling nanofiber scaffolds (5).

Translational Technologies

The translational application of stem cells for the treatment of a number of disorders is the ultimate goal for the majority of stem cell research. In this issue, the application of Chinese herbal medicines and herb extracts in degenerative diseases and their potential molecular mechanisms with respect to endogenous stem cell activity is reviewed (12). Additional reviews also cover the treatment of neurodegenerative disorders including stroke, Alzheimer's disease, and amyotrophic lateral sclerosis using mononuclear cells derived from umbilical cord blood, and menstrual blood-derived stem cells (18), as well as other means to restore brain tissue following stroke, including a free radical scavenger (Edaravone) and a biomaterial scaffold [polydimethysiloxane-tetraethoxysilane (PDMS-TEOS)] with vascular endothelial growth factor (VEGF) (20). This compares with the previous meeting at which the effects of glial cell line-derived neurotrophic factor (GDNF), antioxidant therapy, and stem cell transplantation with or without scaffolds was discussed by Yamashita et al. (21). An extensive review on the potential of umbilical cord blood for the treatment of stroke was also reported by Park et al., who focused on the possible mechanisms of the beneficial effects in reducing ischemic brain injury. This included injured cell replacement, endo/exogenous neurogenesis, enhanced expression of anti-inflammatory cytokines interleukin-10 (IL-10), growth and neurotrophic factors [nerve growth factor (NGF), basic fibroblast growth factor (bFGF)], proangiogenic cytokines (VEGF), and antioxidants as well as reductions in inflammatory cytokines [tumor necrosis factor-α (TNFα)] and free radicals (17).

Additional previously published translational studies include the use of mesenchymal stem cells for the treatment of musculoskeletal diseases, immune modulation, post-myocardial infarction, liver cirrhosis, and ocular diseases by Kuo et al. (10) and endothelial progenitor cells in cardiovascular diseases by Hung et al. (9). The latter includes a review of the clinical trials using these cells in chronic ischemic heart disease, and in coronary artery disease and a discussion of the possible molecular mechanisms including homing factors, angiogenesis molecules, and cytokines.

Linked with the reproductive research looking at endogenous neurogenesis mentioned earlier (11) is the review of the effects of physical exercise on neurogenesis and its ability to counteract stress by Yau et al. (22).

The review of the effects of lithium as a clinical treatment by Young (23) at the previous meeting ties in with the fourth important area: cancer stem cells, because one of the molecular mechanisms of lithium is through glycogen synthetase kinase-3β (GSK3β), which is an important target for new drug development in regenerative medicine and cancer therapy.

Cancer Stem Cells

This is an increasingly important field of stem cell research, as highlighted by the general review of Chen et al. (1). In this article they look at specific markers and the intracellular signal pathways of cancer stem cells in hematopoietic system, brain, breast, lung, ovary, pancreas, and prostate. Cho et al. previously reported on the use of dendritic cell-based immunotherapy for the treatment of malignant gliomas (2) and they follow this up in the current issue looking at the role of CD133⁺ cancer stem cells in this disorder. They describe the characteristics of glioblostoma multiforme stem cells with respect to oncogene expression and their control by micro-RNA. The authors also discuss future directions to treat cancer stem cells by controlling their differentiating signal pathways (3).

Lastly, Ling et al. reviewed a novel method to culture prostate cancer stem cells, in which they prevented them from self-renewal as well as differentiation by using self-assembled peptides (14).

Main Themes of the Fourth PPSSCR in 2011

Future prospects for stem cell research will be highlighted at the 2011 PPSSCR to be held April 15—18, 2011 in Taichung, Taiwan. This meeting will be focused on the translational sciences, including regeneration of corticospinal tracts in patients with stroke, spinal cord injury, cerebral palsy, head injury, congenital disease, or autoimmune diseases by using stem cells or stem cells carrying specific genes or in combination with biomaterials. Stem cell therapies in cardiac, hepatic, orthopedic, metabolic, and hematologic diseases will also be thoroughly presented and discussed.