Differentiation of Human Embryonic Stem Cells into Engrafting Myogenic Precursor Cells

Degenerative muscle diseases affect muscle tissue integrity and function. Human embryonic stem cells (hESC) are an attractive source of cells to use in regenerative therapies due to their unlimited capacity to divide and ability to specialize into a wide variety of cell types. A practical way to derive therapeutic myogenic stem cells from hESC is lacking. In this study, we demonstrate the development of two serum-free conditions to direct the differentiation of hESC towards a myogenic precursor state. Using TGFß and PI3Kinase inhibitors in combination with bFGF we showed that one week of differentiation is sufficient for hESC to specialize into PAX3+/PAX7+ myogenic precursor cells. These cells also possess the capacity to further differentiate in vitro into more specialized myogenic cells that express MYOD, Myogenin, Desmin and MYHC, and showed engraftment in vivo upon transplantation in immunodeficient mice. Ex vivo myomechanical studies of dystrophic mouse hindlimb muscle showed functional improvement one month post-transplantation. In summary, this study describes a promising system to derive engrafting muscle precursor cells solely using chemical substances in serum-free conditions and without genetic manipulation.

Hyperthermia has Consistently Improved the Efficacy of Radiotherapy and Chemotherapy for Many Types of Cancers

Cancer stem-like cells (CSCs) are a subset of cancer cells that are resistant to conventional radiotherapy and chemotherapy. As such, CSCs have been recognized as playing a large role in tumor initiation and recurrence. Although hyperthermia is broadly used in cancer treatment either alone or in combination with radio- or chemo-therapy, its potential to target CSCs is not well understood. In this review, we discuss different types of hyperthermia and potential mechanisms of action in cancer treatment, particularly in regards to killing CSCs.

Subcutaneous DL Technique Has Proven To Be an Adequate Host for Human Embryonic Stem Cells

Islet transplantation has become an important treatment modality for Type 1 Diabetes Mellitus (T1DM); nonetheless, the procedure may be limited by donor availability. An alternative has been the increasing use of cellular therapies derived from human Embryonic Stem Cells (hESC), showing very promising results in maturation, yield and ultimately, in insulin secretion in response to adequate stimuli. We recently developed a new technique for cellular transplantation under the skin. This manuscript evaluates the capabilities of the pre-vascularized Device-Less (DL) site to allow transplantation of Pancreatic Endoderm (PE) cells differentiated from hESC to treat diabetes mellitus. Fifty immunodeficient mice, n = 25 diabetic and n = 25 non-diabetic, were transplanted with PE cells. Animals were followed for 22 weeks and grafts were retrieved to evaluate engraftment and subsequent maturation. Diabetic mice showed slightly better engraftment (48% vs. 36%, p = 0.19) and secreted higher concentration of human C-peptide upon glucose stimulation (0.32 ± 0.15 ng/mL vs. 0.13 ± 0.09 ng/mL, p = 0.30), although differences were not significant. This maturation was not sufficient to successfully reverse diabetes. Monomorphic cystic changes were detected in 12% and 8%, respectively (diabetics vs. non-diabetics, p = 0.32) and all grafts seemed to be adequately contained by the surrounding collagen wall within the DL space. Our findings support the capabilities of the DL site to host PE cells and allow safe maturation as a new strategy to treat diabetes.