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Parkinson’s disease (PD) causes motor dysfunction and dopaminergic cell death. Drug treatments can effectively reduce symptoms but often cause unwanted side effects. Stem cell therapies using cell replacement or indirect beneficial secretomes have recently emerged as potential therapeutic strategies. Although various types of stem cells have been proposed as possible candidates, adipose-derived stem cells (ADSCs) are easily obtainable, more abundant, less ethically disputed, and able to differentiate into multiple cell lineages. However, treatment of PD using adult stem cells is known to be less efficacious than neuron or embryonic stem cell transplantation. Therefore, improved therapies are urgently needed. n -Butylidenephthalide (BP), which is extracted from Angelica sinensis , has been shown to have anti-inflammatory and neuroprotective effects. Indeed, we previously demonstrated that BP treatment of ADSCs enhances the expression of neurogenesis and homing factors such as nuclear receptor related 1 protein, stromal-derived factor 1, and brain-derived neurotrophic factor. In the present study, we examined the ability of BP-pretreated ADSC transplantation to improve PD motor symptoms and protect dopamine neurons in a mouse model of PD. We evaluated the results using neuronal behavior tests such as beam walking, rotarod, and locomotor activity tests. ADSCs with or without BP pretreatment were transplanted into the striatum. Our findings demonstrated that ADSC transplantation improved motor abilities with varied efficacies and that BP stimulation improved the therapeutic effects of transplantation. Dopaminergic cell numbers returned to normal in ADSC-transplanted mice after 22 d. In summary, stimulating ADSCs with BP improved PD recovery efficiency. Thus, our results provide important new strategies to improve stem cell therapies for neurodegenerative diseases in future studies.

Stroke is a result of cerebral ischemia that triggers a cascade of both physiological and biochemical events. No effective treatment is available for stroke; however, stem cells have the potential to rescue tissue from the effects of stroke. Adipose-derived stem cells (ADSCs) are an abundant source of adult stem cells; therefore, ADSC therapy can be considered as a future strategy for regenerative medicine. However, more research is required to improve the effectiveness of transplanted ADSCs as a treatment for stroke in the mouse stroke model. Ligustilide, isolated from the herb Angelica sinensis , exhibits a protective effect on neurons and inhibits inflammation. We also demonstrated that ligustilide treatment increases the expression levels of homing factors such as SDF-1 and CXCR4. In the present study, we evaluated the therapeutic effects of ADSC transplantation and ligustilide treatment in a mouse thromboembolic stroke model by behavioral tests, including beam walking, locomotor activity, and rotarod analysis. ADSCs pretreated with ligustilide were transplanted into the brains of stroke mice. The results showed that the therapeutic effect of ADSCs pretreated with ligustilide was better than that of ADSCs without ligustilide pretreatment. There was no difference between the recovery of mice treated by ADSC transplantation combined with subcutaneous ligustilide injection and that of mice treated only with ADSCs. The TUNEL assay showed fewer apoptotic cells in the brains of mice transplanted with ADSCs pretreated with ligustilide as well as in those without pretreatment. In summary, pretreatment of ADSCs with ligustilide improves the therapeutic efficacy of ADSC transplantation. The results of this study will help improve stem cell therapies being developed for future clinical applications.

Cardiovascular diseases are related to many risk factors, such as diabetes, high blood pressure, smoking, and obesity. Myocardial infarction (MI), a cardiovascular disease, is the most common cause of cardiomyocyte death. In MI, hypoxia induces cardiomyocyte apoptosis; in particular, diabetes combined with MI has a synergistic effect that exacerbates cardiomyocyte death. The hypoxia-inducible factor-1α (HIF1α) transcriptional factor and a BH-3 only protein, Bcl-2 adenovirus E1B 19-kDa interacting protein 3 (BNIP3), are known to play fundamental roles in both adaptive and cell death processes in response to hypoxia. In addition, most cardioprotective studies used H9c2 cells that were not beating, so H9c2 cells may not be the best model for testing cardioprotective effects. Embryonic stem cells (ESCs) are pluripotent stem cells that are able to differentiate into several types of cells, including cardiomyocytes. In this study, we reveal a simple method to differentiate ESCs into cardiomyocytes by using poly-d-lysine-coated plates combined with ITS and N2-containing medium and characterized the ESC-derived cardiomyocytes by cardiomyocyte marker staining. The ESC-derived cardiomyocytes were used to investigate the protective effect of salvianolic acid B (Sal-B) in high glucose combined with hypoxic conditions to mimic diabetes patients with ischemia. The results of MTT and TUNEL assays indicate that Sal-B suppresses the apoptotic effect of treatment with high glucose combined with hypoxia in ESC-derived cardiomyocytes. In particular, Sal-B inhibited HIF1α, BNIP3, and cleavage caspase 3 expression levels, thereby suppressing apoptosis. This is the first study to mention the correlation between BNIP3 and Sal-B for cardioprotective effects. In conclusion, we suggest that Sal-B may be suitable for use as a future cardioprotective medicine.

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are considered the most powerful in terms of differentiating into three-germ-layer cells. However, maintaining self-renewing ESCs and iPSCs in vitro requires leukemia-induced factor (LIF), an expensive reagent. Here we describe a less expensive compound that may serve as a LIF substitute—salvianolic acid B (Sal B), a Salvia miltiorrhiza extract. We found that Sal B is capable of upregulating Oct4 and Sox2, two genes considered important for the maintenance of ESC pluripotency. Our MTT data indicate that instead of triggering cell death, Sal B induced cell proliferation, especially at optimum concentrations of 0.01 nM and 0.1 nM. Other results indicate that compared to non-LIF controls, Sal B-treated ESCs expressed higher levels of several stem cell markers while still maintaining differentiation into three-germ-layer cells after six passages. Further, we found that Sal B triggers the Jak2–Stat3 and EGFR–ERK1/2 signaling pathways. Following Sal B treatment, (a) levels of phosphorylated (p)-Jak2, p-Stat3, p-EGFR, and p-ERK proteins all increased; (b) these increases were suppressed by AG490 (a Jak2 inhibitor) and ZD1839 (an EGFR inhibitor); and (c) cytokines associated with the Jak2–Stat3 signaling pathway were upregulated. Our findings suggest that Sal B can be used as a LIF replacement for maintaining ESC pluripotency while increasing cell proliferation.

Stem cells are capable of self-renewal and differentiation into a wide range of cell types with multiple clinical and therapeutic applications. Stem cells are providing hope for many diseases that currently lack effective therapeutic methods, including stroke, amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease. Embryonic stem (ES) cells were originally targeted for differentiation into functional dopamine neurons for cell therapy. Today, induced pluripotent stem (iPS) cells are being tested for such purposes as generating functional dopamine neurons and treating a rat model of Parkinson's disease. In addition, neural stem cell and mesenchymal stem cells are also being used in neurodegenerative disorder therapies for stroke and Parkinson's disease. Although stem cell therapy is still in its infancy, it will likely become a powerful tool for many diseases that currently do not have effective therapeutic approaches. In this article, we discuss current research on the potential application of neural stem cells, mesenchymal stem cells, ES cells, and iPS cells to neurodegenerative disorders.

Stem cells are capable of self-renewal and differentiation into a wide range of cell types with multiple clinical therapeutic applications. The two most important issues associated with embryonic stem (ES) cells are immune rejection and medical ethics. In 2006, induced pluripotent (iPS) cells were generated from somatic cells via the introduction of four transcriptional factors: OCT4, SOX2, c-MYC, and KLF4. Researchers found that iPS cell morphology, proliferation, surface antigens, gene expression, telomerase activity, and the epigenetic status of pluripotent cell-specific genes were similar to the same characteristics in ES cells. iPS cells are capable of overcoming hurdles associated with ES cells due to their generation from mature somatic cells (e.g., fibroblasts). For this reason, iPS cells are considered an increasingly important cell therapy technology. iPS cell production entails the use of retroviruses, lentiviruses, adenoviruses, plasmid transfections, transposons, or recombinant proteins. In this article we discuss the advantages and limitations of each strategy and address issues associated with clinical trials, including the potential for liver tumor formation and low generation efficiency.

For many years, cancer research has focused on the adult stem cells present in malignant tumors. It is believed that current cancer treatments sometimes fail because they do not target these cells. According to classic models of carcinogenesis, these events can occur in any cell. In contrast, the cancer stem cell (CSC) hypothesis states that the preferential targets of oncogenic transformation are tissue stem cells or early progenitor cells that have acquired the potential for self-renewal. These tumor-initiating cells, or CSCs, in turn, are characterized by their ability to undergo self-renewal, a process that drives tumorigenesis and differentiation, which contributes to the cellular heterogeneity of tumors. Herein, we discuss the definitions and properties of CSCs in the major human cancers.