Volume 3, Issue 4, April 2014

The author proposes a novel mechanism to explain why leukemia stem cells (LSCs) are refractory to tyrosine kinase inhibitors in which Bcr-Abl signaling is fundamentally different in LSCs compared with nonstem leukemia cells and LSCs rely on kinase-independent Bcr-Abl signaling for survival.

This study generated an induced pluripotent stem cell (iPSC) model of hypoplastic left heart syndrome (HLHS) malformation and characterized the properties of cardiac myocytes (CMs) differentiated from these and control-iPSC lines. CMs derived from an HLHS patient demonstrate a number of marker expression and functional differences to human embryonic stem cells/control iPSC-derived CMs, thus providing some evidence that cardiomyocyte-specific factors may influence the risk of HLHS.

In this study, a novel, stepwise chemical protocol is described for the differentiation of human embryonic stem cells and induced pluripotent stem cells into functional retinal ganglion cells. These data demonstrate that a single chemical (the Notch inhibitor N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester [DAPT]) can induce PAX6/RX-positive stem cells to undergo differentiation into functional retinal ganglion cells.

This study shows that chondrocytes from autologous chondrocyte implantation donors can be efficiently reprogrammed into induced pluripotent stem cells using a nonintegrating method based on mRNA delivery. Results suggest that RNA-based technology eliminates the risk of genomic integrations or aberrations, an important step toward a clinical-grade cell source for regenerative medicine such as treatment of cartilage defects and osteoarthritis.

The current review describes the different reprogramming strategies that can give rise to cardiomyocytes for regenerative medicine purposes. The advantages and shortcomings of each strategy for cardiac regeneration are discussed, along with the hurdles that need to be overcome on the road to clinical translation.

Adult neural progenitor cells (aNPC) are a potential autologous cell source for cell replacement in neurologic diseases or for cell-based gene therapy of neurometabolic diseases. Our data show that white matter aNPC are multipotent neural progenitor cells (NPC) with long-term expandability similar to NPC from hippocampus, making them a more easily accessible source for possible autologous NPC-based treatment strategies.

A method was developed to specifically isolate neural progenitor cells (NPCs) from postmortem adult human brains based on the expression of the specific human adult neural stem/progenitor cell marker glial fibrillary acidic protein δ. This study shows that a pure population of NPCs can be isolated from the adult human subventricular zone (SVZ), which is highly instrumental for developing future therapies based on stimulating endogenous SVZ neurogenesis.

This study used human junctional adhesion molecule A (JAM-A)-modified human mesenchymal stem cells (MSCs) to repair hair follicle (HF) abnormalities in BALB/c nu/nu mice. Results indicated that JAM-A^ov MSCs improved hair formation in nude mice through HF structure remodeling.

This study investigated whether it is possible to isolate pancreatic endocrine progenitors from differentiating human embryonic stem cell (hESC) cultures by lineage tracing of NGN3. Results indicate that NGN3⁺ cells represent pancreatic endocrine progenitors in humans. This hESC reporter line is a unique tool that may aid in gaining insight into the developmental mechanisms underlying fate choices in human pancreas and in developing cell-based therapies.

The growing number of human disease models made with patient-specific induced pluripotent stem cells (iPSCs) has made it possible to conduct research on a wide range of disorders. This review surveys the incorporation of iPSC technology into drug therapy development, which holds promise as a powerful and nuanced approach to personalized medicine.

Hutchinson-Gilford progeria syndrome is a rare congenital disease characterized by premature aging in children. The results of this systematic comparative study of the three main treatments currently administered or proposed to progeria-affected children reveal the complexity of the modes of action of different drugs and underscore the use of induced pluripotent stem cell derivatives as a critical and powerful tool for standardized, comparative pharmacological studies.

This paper presents a culture system that can be used as an in vitro surrogate for xenotransplantation and that has the potential to dramatically increase the throughput of the investigation of leukemia-initiating cells, providing the means to identify and target the functionality of the different signaling pathways involved in the maintenance and resistance of leukemia-initiating cells to improve acute myeloid leukemia treatments.

This study aimed to review the experience with 13 consecutive cases of cranio-maxillofacial hard-tissue defects at four anatomically different sites, namely frontal sinus (3 cases), cranial bone (5 cases), mandible (3 cases), and nasal septum (2 cases). Successful integration of the construct to the surrounding skeleton was noted in 10 of the 13 cases.

Bacterial and fungal infections are the leading cause of morbidity and mortality in neutropenic patients. Transfusing the patient with neutrophil-like cells manufactured in the laboratory from hematopoietic stem and progenitor cells enriched from umbilical cord blood can potentially prevent fulminant infections. The authors review the rationale for focusing research efforts toward ex vivo neutrophil production.